Endoscopic ultrasonographic study of the azygos vein before and after endoscopic obliteration of esophagogastric varices by injection sclerotherapy.
The azygos vein plays an important role as a drainage system for the superior portosystemic collateral circulation in portal hypertensive patients. Endoscopic ultrasonography (EUS) and Doppler EUS allow the performance of hemodynamic studies of the azygos vein. In this study, we observed the changes in the azygos vein which occur with variceal obliteration by endoscopic injection sclerotherapy (EIS). We recruited patients with portal hypertension and bleeding varices who were not on portal pressure-lowering agents and who were scheduled for the EIS program. EUS was performed in these patients to study the azygos vein at the start of EIS. The azygos vein diameter, maximal velocity (Vmax), and blood flow volume index (BFVI) were measured. After variceal obliteration and within 1 week, another EUS study of the azygos vein was carried out. Out of 40 patients recruited into the study variceal obliteration and EUS assessment of the azygos vein, within 1 week of obliteration, was achieved in 33. We noticed a significant increase in azygos vein diameter (P<0.001) and BFVI (P=0.001) following variceal obliteration. No significant change was observed in Vmax (P>0.05). In one patient, marked caliber irregularities were observed in the azygos vein after variceal obliteration. Using EUS and Doppler EUS, hemodynamic studies of the azygos vein blood flow can be performed, allowing the monitoring of the effects of EIS and variceal obliteration on the superior portosystemic collateral circulation. The clinical significance of the observed changes in azygos blood flow that occur with variceal obliteration should be investigated in further studies and correlated with short-term and long-term outcome.


The impact of environmental cleanliness and cultural factors on child health in Africa.
Africa is a region with abundant natural resources, but the child mortality rate is higher. Despite World Health Organization (WHO) support, the region remained the highest with the number of child mortality rate. Given this fact, this study examines the role of environmental degradation, clean water source, and sanitation facilities on child mortality and life expectancy/longevity in Africa. To achieve this objective, we employ pooled regression and system generalized method of moment (S-GMM) on 33 African countries between 2000 and 2014. We found that environmental degradation is positively related to child mortality and life expectancy or longevity. However, clean water sources and sanitation facilities help to reduce the child mortality rate and help to improve life expectancy. Also, we found cultural norms improve child mortality and life expectancy. Our results imply that African countries are benefitting from cultural values, clean water sources, and sanitation facilities.


Interoceptive awareness, positive affect, and decision making in major depressive disorder.
Little work has examined the relation between interoceptive awareness and symptoms of Major Depressive Disorder (MDD). Existing research suggests that depressed individuals exhibit impaired heartbeat perception, though the results of this research have been equivocal. Importantly, depressed participants in these studies have had comorbid anxiety disorders, making it difficult to draw inferences about interoceptive awareness in MDD. The current study addresses this issue by assessing heartbeat perception in depressed women without current anxiety disorders and exploring the relation between interoception and perturbations in both affective intensity and decision making, components of MDD postulated to be related to bodily awareness. Depressed women without concurrent anxiety disorders (n=25) and never-disordered controls (n=36) performed a heartbeat perception task. Participants completed the self-report Affect Intensity Measure (AIM), and decision-making difficulty was assessed in MDD participants using the Structured Clinical Interview for DSM-IV. Depressed women exhibited poorer heartbeat perception accuracy than did control participants. Impaired accuracy in MDD participants was associated with reduced positive affectivity and difficulty in decision making. Our sample was composed exclusively of females and was heterogeneous with respect to treatment status, thereby limiting our ability to generalize results to depressed males and to exclude the contribution of exogenous factors to the observed group differences. Results of this study suggest that for depressed individuals without anxiety comorbidities, disrupted perception of bodily responses reduces both the experience of positive arousal and the ability to use interoceptive feedback to inform decision making.


Channel-free shear driven circular liquid chromatography.
Shear stress has been exploited within a channel-free rotating plate system for the circular chromatographic separation of model analytes.


Differential Response of Extracellular Proteases of Trichoderma Harzianum Against Fungal Phytopathogens.
In the present study, production of extracellular proteases by Trichoderma harzianum was evaluated based on the relative gene expression and spectrophotometric assay. The fungal isolates were grown in Czapek Dox Broth medium supplemented with deactivated mycelium of plant fungal pathogens such as Fusarium oxysporum, Colletotrichum capsici, Gloeocercospora sorghi, and Colletotrichum truncatum. The maximum protease activity was detected after 48 h of incubation against Colletotrichum spp. Similarly in qRT-PCR, the relative gene expression of four proteases varied from 48 to 96 h against host pathogens in a time-independent manner. Among proteases, statistically significant upregulation of asp, asp, and srp was observed against Colletotrichum spp., followed by F. oxysporum. But in the case of pepM22, maximum upregulation was observed against F. oxysporum. The variation in enzyme assay and qRT-PCR of proteases at different time intervals against various fungal phytopathogens could be due to the limitation of using casein as a substrate for all types of proteases or protease-encoding transcripts selected for qRT-PCR, which may not be true representative of total protease activity.


Isolated tracheobronchial mucormycosis: Report of a case and systematic review of literature.
Isolated tracheobronchial mucormycosis (ITBM) is an uncommonly reported entity. Herein, we report a case of ITBM following coronavirus disease 2019 (COVID-19) and perform a systematic review of the literature. A 45-year-old gentleman with poorly controlled diabetes mellitus presented with cough, streaky haemoptysis, and hoarseness of voice 2 weeks after mild COVID-19 illness. Computed tomography and flexible bronchoscopy suggested the presence of a tracheal mass, which was spontaneously expectorated. Histopathological examination of the mass confirmed invasive ITBM. The patient had complete clinical and radiological resolution with glycaemic control, posaconazole, and inhaled amphotericin B (8 weeks). Our systematic review of the literature identified 25 additional cases of isolated airway invasive mucormycosis. The median age of the 26 subjects (58.3% men) was 46 years. Diabetes mellitus (79.2%) was the most common risk factor. Uncommon conditions such as anastomosis site mucormycosis (in two lung transplant recipients), post-viral illness (post-COVID-19 [n = 3], and influenza [n = 1]), and post-intubation mucormycosis (n = 1) were noted in a few. Three patients died before treatment initiation. Systemic antifungals were used in most patients (commonly amphotericin B). Inhalation (5/26; 19.2%) or bronchoscopic instillation (1/26; 3.8%) of amphotericin B and surgery (6/26; 23.1%) were performed in some patients. The case-fatality rate was 50%, primarily attributed to massive haemoptysis. Isolated tracheobronchial mucormycosis is a rare disease. Bronchoscopy helps in early diagnosis. Management with antifungals and control of risk factors is required since surgery may not be feasible.


Septic arthritis caused by Streptococcus suis serotype 2.
A case of septic arthritis and septicaemia due to Streptococcus suis serotype 2 is reported. To our knowledge, this is the first case in which the causative organism has been isolated from the joint-fluid. Involvement of joints is a feature of S. suis infection in pigs, and may be more common in human beings than previously realised. Infectious arthritis caused by beta-haemolytic streptococci may be due to S. suis and result from contact with pigs or raw pork.


Improved rapid amplification of cDNA ends (RACE) for mapping both the 5' and 3' terminal sequences of paramyxovirus genomes.
Rapid amplification of cDNA ends (RACE) is a powerful PCR-based technique for determination of RNA terminal sequences. However, most of the RACE methods reported in the literature are developed specifically for the mapping of eukaryotic transcripts with 3' poly-A tail and 5' cap structure. In this study, an improved RACE strategy was developed which allows both 5' and 3' RACE of paramyxovirus genomic RNA using the same set of common molecular biology reagents without having to rely on expensive RACE kits. Mapping of RNA genome terminal sequences is an essential part of characterizing novel paramyxoviruses since these sequences contain important signals for genome replication and transcription, and are important molecular markers for studying virus evolution. The usefulness of this strategy was demonstrated by rapid characterization of both genome ends for a novel paramyxovirus recently isolated from human kidney primary cells. The RACE strategy described in this paper is simple, cost-effective and can be used to map genome ends of any RNA viruses.


[Effects of Tai Chi exercise in elderly with knee osteoarthritis].
This study was to determine whether the Sun-style 24 forms of Tai Chi exercise improve pain, stiffness, disability, knee joint motion, mobility, balance or falling. Forty-six community-dwelling elderly subjects (mean age, 75.46+/-6.28) voluntarily participated in an intervention group of either 24 forms of Sun-style Tai Chi for 60 min, 2 times per week for 12 weeks or a control group. A non-equivalent pretest-posttest design was used. Independent t-test and ANCOVA were used to examine group differences by using SPSS12.0. The experimental group had significantly less pain (F=7.60, p=.008) and stiffness (t=-3.19, p=.003) than the control group. Also there were significant improvements in knee joint motion on the right knee (t=2.44, p=.019), left knee (t=2.30, p=.026), rising time (F=8.03, p=.07), balance on the left single leg test (t=2.20, p=.033), and fear of falling (t=-2.33, p=.024) in the Tai Chi exercise group. No significant group differences were found in disability and falls efficacy. The Sun-style 24 forms Tai Chi exercise is effective in decreasing pain, stiffness, fear of falling and it improves balance, rising time, and knee joint motion. We suggest a continuing long term intervention to decrease disability and increase efficacy concerning falls.


The Application of Single-Cell RNA Sequencing in Studies of Autoimmune Diseases: a Comprehensive Review.
Complex composition is one of the most important features of the immune system, involving many types of organs, tissues, cells, and molecules that perform immune functions. The normal function of each component of the immune system is the guarantee for maintaining the relatively stable immune function of the body. When the self-immune tolerance mechanism of the body is unregulated or destroyed, the immune system reacts to autoantigens, resulting in damage to self-tissues and organs or an immunopathological state with abnormal functions. Autoimmune diseases are diverse, and their pathogenesis is complicated. Various immune cells and their interactions play significant roles in the occurrence and development of diseases. The solution to heterogeneity of immune cells is the basic science and translational understanding of how genes and the environment interact to induce disease so that we can develop personalized medicine, a goal that has to this point eluded scientists. Single-cell RNA sequencing (scRNA-Seq) refers to a new technique allowing high-throughput sequencing analysis of the whole transcriptome to reveal the gene expression status of individual cells. It has emerged as an indispensable tool in the field of life science research, and can help identify the complex mechanism of cell heterogeneity, discover new cell subsets, and help uncover the molecular mechanisms of pathogenesis, the evolution of disorders, and drug resistance. This information can provide us with new strategies for diagnosis and prognostic evaluation, as well as monitoring treatment responses. In this review, we summarize the crucial experimental procedures used for single-cell RNA sequencing, and the current applications of this technique to study autoimmune diseases are described in detail. This technique will be widely used in more in-depth studies of autoimmune diseases and will contribute to the diagnosis and therapies of these disorders.


Multiple congenital aneurysms in childhood: report of a case.
This paper reports the case of a girl who, at the age of 7 years, presented with a saccular aneurysm of a brachial artery. Over the following 8 years a further 15 aneurysm appeared, involving limb and visceral arteries and the aorta. Some, but not all, of these aneurysms have been operated upon. Complications included renovascular hypertension due to bilateral intrarenal aneurysms. She had been followed up for 15 years. Three other similar cases have been found in the medical literature, and these are also referred to. In two of these cases the affected persons also exhibited some of the other connective tissue anomalies associated with the Ehlers--Danlos syndrome. These were not present in our patient. The relationship between the syndrome of multiple congenital aneurysms and the Ehlers--Danlos syndrome is discussed.


Developmental changes in the sensitivity of the neonatal rat brain to hypoxic/ischemic injury.
Developmental changes in the response of the neonatal rat brain to hypoxic/ischemic injury were examined. Hypoxic/ischemic injury was produced by unilateral carotid ligation followed by exposure to hypoxia in 1- (D1), 3- (D3), 5- (D5) and 7-day-old (D7) rats. Injury was produced in most D7 animals exposed to > or = 120 min of 7.6 or 8% oxygen after carotid ligation. The extent of neuronal injury was variable, ranging from focal neuronal death to massive infarction. In D5 and D3 animals, there was a progressive decline in the extent of neuronal injury in response to hypoxia/ischemia. In the younger animals, bilateral injury was occasionally seen. Sham-operated animals exposed to hypoxia alone had numbers of karyorrhectic neurons similar to normal control animals in all age groups. The underlying developmental changes which account for these differences are not yet known but are likely to be multiple.


Pneumococcal meningitis and etanercept--chance or association?
Rheumatoid arthritis is a severe deforming chronic disease which has major implications for mortality and quality of life. Agents with anti-tumour necrosis factor alpha (TNFalpha) activity are a new modality of therapy, which can significantly reduce the acute inflammation in this condition. However, TNFalpha is a cytokine involved in initiating the protective immune response; consequently, patients receiving this therapy are at increased risk of infection. Etanercept is a recombinant form of the p75 TNF receptor (TNF-RII) dimerised by fusion with a portion of the human IgG1 Fc tail with anti-TNFalpha activity. We report the first case of a patient with rheumatoid arthritis who developed pneumococcal meningitis whilst on etanercept, suggesting a possible association between etanercept and this severe life threatening infection.


Image-guided ablation of postsurgical locoregional recurrence of biopsy-proven well-differentiated thyroid carcinoma.
To evaluate the clinical outcomes of ultrasound-guided percutaneous radiofrequency (RF) ablation and percutaneous ethanol injection (PEI) as salvage therapy for locoregional recurrence after resection of well-differentiated thyroid carcinoma. There were 42 locoregional, biopsy-proven, papillary and follicular thyroid carcinoma lesions (0.5-3.7 cm) treated, 21 with RF ablation and 21 with PEI. Of treated lesions, 35 were located in the lateral compartments, and 7 were located in the central compartment. Data points in the retrospective analysis, determined beforehand by the investigators, were progression at the ablation site, serum thyroglobulin levels before and after the procedure, and procedural complications. Average follow-up after RF ablation was 61.3 months and after PEI was 38.5 months. No progression was detected in the region of ablation for any of the lesions treated with RF ablation. Local progression was detected 4-11 months after ablation in 5 of the 21 lesions treated with PEI, 3 in the lateral compartment and 2 in the central compartment; all of the lesions were successfully retreated with repeat PEI, RF ablation, or surgery. Permanent vocal cord paralysis occurred after one RF ablation procedure of a lateral compartment supraclavicular node. There were no complications after PEI. This case series provides long-term follow-up evidence of the safety and efficacy of ultrasound-guided RF ablation and PEI for control of locoregional recurrence of well-differentiated thyroid carcinoma after surgery.


EspE3 plays a role in the pathogenicity of avian pathogenic Escherichia coli.
APEC encodes multiple virulence factors that have complex pathogenic mechanisms. In this study, we report a virulence factor named EspE3, which can be secreted from APEC. This protein was predicted to have a leucine-rich repeat domain (LRR) and may have a similar function to IpaH class effectors of the type III secretion system (T3SS). For further exploration, the regulatory correlation between the espE3 and ETT2 genes in APEC was analysed. We then assessed the pathogenicity of EspE3, detected it in APEC secretion proteins and screened the proteins of EspE3 that interact with chicken trachea epithelial cells. This study provides data on a new virulence factor for further exploring the pathogenic mechanism of APEC.


Habitat complexity affects benthic harmful dinoflagellate assemblages in the fringing reef of Rawa Island, Malaysia.
Few studies have investigated the effect of fine-scale habitat differences on the dynamics of benthic harmful dinoflagellate assemblages. To determine how these microhabitat differences affect the distribution and abundance of the major benthic harmful dinoflagellate genera in a tropical coral reef ecosystem, a field study was undertaken between April-September 2015 and January 2016 on the shallow reef flat of the fringing reef of Rawa Island, Terengganu, Malaysia. Sampling of benthic dinoflagellates was carried out using an artificial substrate sampling method (fiberglass screens). Benthic microhabitats surrounding the sampling screens were characterized simultaneously from photographs of a 0.25-m2 quadrat based on categories of bottom substrate types. Five taxonomic groups of benthic dinoflagellates, Ostreopsis, Gambierdiscus, Prorocentrum, Amphidinium, and Coolia were identified, and cells were enumerated using a light microscope. The results showed Gambierdiscus was less abundant than other genera throughout the study period, with maximum abundance of 1.2 × 103 cells 100 cm-2. While most taxa were present on reefs with high coral cover, higher cell abundances were observed in reefs with high turf algal cover and coral rubble, with the exception of Ostreopsis, where the abundance reached a maximum of 3.4 × 104 cells 100 cm-2 in habitats with high coral cover. Microhabitat heterogeneity was identified as a key factor governing the benthic harmful dinoflagellate assemblages and may account for much of the observed variability in dominant taxa. This finding has significant implications for the role of variability in the benthic harmful algal bloom (BHAB) outbreaks and the potential in identifying BHAB-related toxin transfer pathways and the key vectors in the food webs.


[The coma awakening unit, between intensive care and rehabilitation].
After intensive care and before classic neurological rehabilitation is possible, patients in an altered state of consciousness are cared for at early stages in so-called coma awakening units. The care involves, on the one hand, the complex support of the patient's awakening from coma as a neurological and existential process, and on the other, support for their families.


The in vitro biosynthesis of dhurrin, the cyanogenic glycoside of Sorghum bicolor.
A microsomal fraction from seedlings of Sorghum bicolor (Linn) Moench has been shown to catalyze the conversion of L-tyrosine to p-hydroxymandelonitrile via p-hydroxyphenylacetaldoxime. This transformation is consistent with the general pathway for cyanogenic glycoside biosynthesis proposed on the basis of in vivo experiments. When the microsomal fraction was combined with a protein fraction from the soluble portion of the cell and uridine diphosphate glucose, it was possible to demonstrate the synthesis of the cyanogenic glycoside dhurrin from L-tyrosine.


Giardiasis in Iowa.
The author discusses transmission and case distribution of the parasitic disease giardiasis and why it should be made reportable.


Nanorobots: Future in dentistry.
The purpose of this paper is to review the phenomenon of nanotechnology as it might apply to dentistry as a new field called nanodentistry. Treatment possibilities might include the application of nanotechnology to local anesthesia, dentition renaturalization, the permanent cure for hypersensitivity, complete orthodontic realignment in a single visit, covalently bonded diamondized enamel, and continuous oral health maintenance using mechanical dentifrobots. Dental nanorobots could be constructed to destroy caries-causing bacteria or to repair tooth blemishes where decay has set in, by using a computer to direct these tiny workers in their tasks. Dental nanorobots might be programed to use specific motility mechanisms to crawl or swim through human tissue with navigational precision, to acquire energy, to sense and manipulate their surroundings, to achieve safe cytopenetration, and to use any of a multitude of techniques to monitor, interrupt, or alter nerve-impulse traffic in individual nerve cells in real time.


Prose memory in patients with idiopathic Parkinson's disease.
The findings of previous studies have suggested that verbal memory impairments were observed in people suffering from Parkinson's disease (PD). Very few studies have examined the comprehensive profile of prose memory deficits that challenges people with PD. Prose memory of 19 patients with PD was examined. Their performance in three constructs, namely recall accuracy, temporal sequence, and distortions, during immediate, delayed and recognition trials was studied. The patients with PD performed significantly worse in recall accuracy and temporal sequencing of information in the immediate recall trial. During the recognition trial, they made more false alarms than their healthy counterparts. Our findings confirm that the performance of people with PD in immediate recall of a prose was impaired. However, the level of performance in subsequent learning and delayed recall trials became comparable to that of the normal controls. The deficit remaining after multiple learning trials was the significantly high false alarms committed in the recognition trial. Our findings highlight the importance of qualitative analysis, in addition to quantitative evaluation, of prose memory in PD.


Role of dorsomedial thalamic nucleus and piriform cortex in processing olfactory information.
Four experiments were conducted to characterize the role of primary and secondary olfactory projection areas (piriform cortex and dorsomedial thalamic nucleus (DMN] in olfactory information processing. Rats had to learn to discriminate between odors that were simultaneously released from different arms of an automated olfactory maze. When standard training conditions were used, damage of the DMN severely impaired both preoperatively trained and naive animals in acquiring an odor discrimination set (i.e. in most problems no learning was demonstrated). An additional group of DMN animals that received 4 times the standard amount of daily trials was unable to acquire the first two problems but successfully solved the third and all subsequent discriminations. Analysis of performance patterns suggested that destruction of the DMN initially leads to a strong procedural impairment that can be overcome by extensive training. After solving the third problem the animals with DMN damage required much less training to reach the learning criterion but generally made more errors than controls. Transfer of savings rarely occurred when a problem was repeated. Whether this secondary learning deficit observed in later discriminations is due to a specific effect of the lesion on the encoding of olfactory cues and thus on memory formation, or due to a disturbance in the regulation of emotional factors such as motivation, arousal, and attention is discussed. Lesions of the thalamus that spared the DMN had no effect on learning or retention of olfactory discriminations. Animals with ablations of the piriform cortex only acquired odor discriminations if they had been trained in the olfactory maze before the lesion. Moreover, their performance depended on the odor quality: they had great difficulty learning complex cues consisting of several odorants and learned simple odors virtually identical to control rats. The results indicate that an intact piriform cortex is needed to acquire the procedures involved to perform an olfactory discrimination task as well as to build neural representations of olfactory cues.


The diagnostic experience of polycystic ovary syndrome: A scoping review of patient perspectives.
Polycystic Ovary Syndrome (PCOS) is a common endocrine condition with a complex diagnostic process. The present study aims to understand patient perceptions of the process of PCOS diagnosis, and how challenges during diagnosis can influence patient understanding of PCOS and trust in healthcare providers (HCPs). A scoping review framework was followed. Six databases were searched for patient experiences of PCOS diagnosis, between January 2006 - July 2021. Data extraction and thematic analyses were conducted. Of the 338 studies screened, 21 studies fulfilled the inclusion criteria. Patient experiences of the diagnostic process were stratified into three themes: emotional, negotiating, and incomplete. As a result of these experiences, patients begin to perceive their HCPs as lacking knowledge and empathy. There are prevailing gaps in how PCOS diagnostic criteria are understood and applied in the clinical setting, leading to a lengthy diagnostic process. Additionally, poor HCP communication negatively affects patient trust in HCPs. Practicing patient-centered care and empowering patients by addressing their specific information needs are essential to improving the diagnostic experience and care of individuals living with PCOS. These recommendations may also apply to the diagnosis of other complex chronic conditions.


Inhaled anesthetics in horses.
Inhaled agents represent an important and useful class of drugs for equine anesthesia. This article reviews the ether-type anesthetics in contemporary use, their uptake and elimination, their mechanisms of action, and their desirable and undesirable effects in horses.


Curcumin for attention-deficit-hyperactivity disorder: a systematic review and preliminary behavioral investigation.
Curcumin has protective actions in neuropsychiatric disorders, acting as a neuroprotective agent. As a first approach, the study aimed at a systematic review of the potential effects of curcumin on cognitive performance for attention-deficit-hyperactivity disorder (ADHD). This research was carried out in the databases of PubMed, Embase, SciELO, the Cochrane Central Register of Controlled Trials (CENTRAL), the Web of Science, and the Grey literature. Upon discovering the scarcity of relevant studies, and knowing that curcumin might have an ADHD hyperactive and anxious behavior, the study proposed to evaluate the effects of curcumin in an ADHD phenotype of spontaneously hypertensive Wistar rats (SHR). No studies were found that related to curcumin and ADHD. Fifteen SHRs were then divided into separate groups that received water (1 mg/kg/day), curcumin (50 mg/kg/day), or methylphenidate (1 mg/kg/day) for 42 days. Behavioral tests to assess activity (Open Field Test), anxiety and impulsivity (Elevated Plus-Maze, and Social Interaction), and memory (Y-Maze, and the Object Recognition Test) were all performed. The animals that were treated with curcumin showed less anxious and hyperactive behavior, as seen in the Open Field Test and the Social Interaction Test. Anxious behavior was measured by the EPM and was not modulated by any treatment. The results of the Y-Maze Test demonstrated that curcumin improved spatial memory. In the Object Recognition Test, neither the short nor the long-term memory was improved. The treatments that were used in this study beneficially modulated the anxious and hyperactive behavior of the SHR.


A Comparison of Two Models of Risky Sexual Behavior During Late Adolescence.
Two models of risky sexual behavior (RSB) were compared in a community sample of late adolescents (N = 223). For the traumagenic model, early negative sexual experiences were posited to lead to an association between negative affect with sexual relationships. For the cognitive escape model, depressive affect was posited to lead to engagement in RSB as a way to avoid negative emotions. The current study examined whether depression explained the relationship between sexual trauma and RSB, supporting the cognitive escape model, or whether it was sexual trauma that led specifically to RSB, supporting the traumagenic model. Physical trauma experiences were also examined to disentangle the effects of sexual trauma compared to other emotionally distressing events. The study examined whether the results would be moderated by participant sex. For males, support was found for the cognitive escape model but not the traumagenic model. Among males, physical trauma and depression predicted engagement in RSB but sexual trauma did not. For females, support was found for the traumagenic and cognitive escape model. Among females, depression and sexual trauma both uniquely predicted RSB. There was an additional suppressor effect of socioeconomic status in predicting RSB among females. Results suggest that the association of trauma type with RSB depends on participant sex. Implications of the current study for RSB prevention efforts are discussed.


CaMKK2: a novel target for shaping the androgen-regulated tumor ecosystem.
The androgen receptor (AR) is pivotal in the biology of sex hormone-regulated malignancies, with prostate cancer (PC) the most affected tumor. AR signals control the growth, survival, and migration of cancer cells, and they regulate the activation of macrophages, a cell type pivotal to the tumor ecosystem. Intriguingly, CaMKK2 has recently been identified as both an important AR-regulated gene in the context of PC and as a critical regulator of macrophage activation. By contrast, CaMKK2 is barely detectable in normal prostate or immune cells that mediate the response against tumorigenesis. These novel findings suggest that CaMKK2 resides at a critical molecular node that shapes the cancer ecosystem, and identifies this kinase as a novel therapeutic target for sex hormone-regulated cancers.


Nickel Glyoximate Based Metal-Covalent Organic Frameworks for Efficient Photocatalytic Hydrogen Evolution.
Metal-covalent organic frameworks (MCOFs) have been recently received wide attention owing to the homogeneous distribution of active metal centers that are beneficial for enhancing the application potentials. However, metal complex based functional building blocks for MCOFs synthesis are limited. Herein, two new MCOFs (Ni-Py-COF and Ni-Bn-COF) were constructed via a novel nickel glyoximate based building block. Splendid photocatalytic activity on hydrogen evolution from water and great long-term recyclability were achieved using these nickel glyoximate based MCOFs as photocatalysts. Excitingly, even without the addition of Pt co-catalyst, the hydrogen evolution rates (HER) of Ni-Py-COF reached up to 626 μmol g-1 h-1 , which is better than many porous organic polymers. This work not only expands the type of building units for MCOFs, but also provides meaningful insights for developing stable, efficient and earth-abundant photocatalysts toward H2 generation.


Population health model for pharmacist assessment and independent prescribing of statins in an ambulatory care setting.
This study aimed to evaluate the impact of a pharmacist population health initiative on the ability to increase the percentage of patients with atherosclerotic cardiovascular disease (ASCVD) who are on an appropriate statin. Ten primary care clinics in Southwest Washington. The average payer mix across the included clinics is 47% Medicare, 26% commercial, 22% Medicaid, 2% self-pay, and 3% other. Reimbursement-tied statin quality metrics are present in 14.1% of patients' insurance contracts. The primary care pharmacy collaborative drug therapy agreement allows pharmacists to act as prescribers by permitting initiation, adjustment, and monitoring of medication therapy, with the authority historically stemming from referral by the patient's primary care provider to the pharmacist. A novel, population health protocolized prescriptive authority (PPA) initiative was implemented, of which a key component was expanding pharmacists' prescriptive authority to prescribe statins for population health initiatives. Without referral, pharmacists screened, directly outreached to, and prescribed statins for patients with ASCVD who were not on a moderate- or high-intensity statin. Electronic health record (EHR) documentation was updated to better reflect the patient's history and increase metric accuracy. A retrospective analysis of a population health initiative from October 1 to December 31, 2018. The initiative was evaluated on the combined success of initiating patients with ASCVD on moderate- or high-intensity statins and the acceptance rate of EHR corrections. The pharmacy team screened 510 patients. Appropriately dosed statins were initiated for 40.0% of patients, and the EHR was accurately updated in 91.9% of instances. These combined efforts demonstrate 50.5% overall success of pharmacist interventions. Expanding pharmacists' authority to PPA for statin medications in patients not meeting quality metrics increased the number of successful interventions. Pharmacists make a major contribution on improving population health metrics for statins.


Revisiting the Rich's formula: an update about granulomas in human tuberculosis.
The formula proposed by Rich in 1951 explained the formation in a tuberculous lesion in a period that was unknown cellular functions, cytokines and other immunological aspects involved in granuloma formation by tuberculosis; its components are assembled conceptually to explain the pathogenic mechanisms involved in the granulomatous lesion in tuberculosis. In this manuscript, we report an update of Rich's formula based on the new and old concepts about pathogenic mechanisms involved in the granulomatous lesion in tuberculosis. Current knowledge allows us to conclude that the balance between the characteristics of the bacillus and host protective response is necessary to indicate the outcome of pathogenesis, infection or active disease and the necrosis degree of the tuberculosis lesion.


The effect of pregnancy on the frontal plane QRS axis.
The electrical axis of the heart is an important parameter in electrocardiographic assessment. Slight degrees of left axis deviation have been attributed to a horizontal heart position resulting from the mechanical effects of abdominal distension, such as the physiological event of pregnancy. This study was undertaken to establish the validity of this concept.


Water Pollution Increases the Risk of Chytridiomycosis in Mexican Amphibians.
Chytridiomycosis is affecting amphibians worldwide, causing the decline and extinction of several amphibian populations. The disease is caused by the fungus Batrachochytrium dendrobatidis (Bd), a multihost pathogen living in freshwater habitats. While several environmental factors have been associated with the prevalence of Bd and its virulence, the effects of water quality on the pathogen are not clear yet. Some evidence suggests that water pollution may reduce amphibians' immune response and increase prevalence of Bd. To explore this hypothesis, we analyzed the relationship between water quality and the presence of Bd by using spatial data mining of 150 geolocations of Bd in amphibians from 9 families where Bd positive specimens have been previously reported, and water quality in 4,202 lentic and lotic water bodies in Mexico from 2010 to 2021. Our model showed that in the 3 main families where Bd was recorded, its presence is high in locations with low water quality, i.e., water polluted likely contaminated with urban and industrial waste. Using this model, we inferred areas suitable for Bd in Mexico; mainly in poorly studied areas along the gulf and on the pacific slope. We further argue that actions to reduce water pollution should become an integral part of public policies to prevent the spread of Bd and protect amphibians from this deadly pathogen.


A generic scaffold for conversion of peptide ligands into homogenous biosensors.
Numerous peptide ligands including protease recognition sequences, peptides mediating protein-protein interactions, peptide epitopes of antibodies and mimotopes are available which bind molecules of interest. However, there is currently no facile method for the incorporation of these peptides into homogenous detection systems. We present a generalizable method for the incorporation of such peptides into a novel fusion protein framework comprising an enzyme and its inhibitor. The incorporated peptide functions as an allosteric hinge, linking enzyme to its inhibitor. Upon interaction with its cognate analyte, the peptide mediates dissociation of the inhibitor from the enzyme, and facilitates one-step signal generation. Likewise, cleavage of the peptide by a specific protease also causes enzyme-inhibitor dissociation, leading to signal generation. Using the β-lactamase Tem1 and its inhibitor protein as a model scaffold, we show both specific and sensitive (between low nanomolar and mid-picomolar) colorimetric detection of proteases and antibodies within minutes in a homogenous one-step reaction visible to the naked eye. The same scaffold affords in vivo detection of antibody binding and protease function by linking activity to a selectable phenotype in E. coli.


Metformin Improves Mitochondrial Respiratory Activity through Activation of AMPK.
Impaired mitochondrial respiratory activity contributes to the development of insulin resistance in type 2 diabetes. Metformin, a first-line antidiabetic drug, functions mainly by improving patients' hyperglycemia and insulin resistance. However, its mechanism of action is still not well understood. We show here that pharmacological metformin concentration increases mitochondrial respiration, membrane potential, and ATP levels in hepatocytes and a clinically relevant metformin dose increases liver mitochondrial density and complex 1 activity along with improved hyperglycemia in high-fat- diet (HFD)-fed mice. Metformin, functioning through 5' AMP-activated protein kinase (AMPK), promotes mitochondrial fission to improve mitochondrial respiration and restore the mitochondrial life cycle. Furthermore, HFD-fed-mice with liver-specific knockout of AMPKα1/2 subunits exhibit higher blood glucose levels when treated with metformin. Our results demonstrate that activation of AMPK by metformin improves mitochondrial respiration and hyperglycemia in obesity. We also found that supra-pharmacological metformin concentrations reduce adenine nucleotides, resulting in the halt of mitochondrial respiration. These findings suggest a mechanism for metformin's anti-tumor effects.


Conversion of percutaneous ureteral stent to indwelling pigtail stent over guidewire.
A ureteral stent placed percutaneously through a nephrostomy can be readily exchanged endoscopically for a ureteral indwelling pigtail stent over a percutaneous guide wire. Percutaneous antegrade stent placement can sometimes be accomplished when retrograde placement cannot. We report 10 successful conversions to indwelling stent in 11 cases. In 1 case the percutaneous guide wire could not be retrieved endoscopically because of a bleeding tumor in the bladder. No serious difficulties or complications were encountered. The percutaneous approach offers an alternative method of providing internal urinary diversion if retrograde ureteral indwelling stent placement has failed.


Novel epigenetic molecular therapies for imprinting disorders.
Genomic imprinting disorders are caused by the disruption of genomic imprinting processes leading to a deficit or increase of an active allele. Their unique molecular mechanisms underlying imprinted genes offer an opportunity to investigate epigenetic-based therapy for reactivation of an inactive allele or reduction of an active allele. Current treatments are based on managing symptoms, not targeting the molecular mechanisms underlying imprinting disorders. Here, we highlight molecular approaches of therapeutic candidates in preclinical and clinical studies for individual imprinting disorders. These include the significant progress of discovery and testing of small molecules, antisense oligonucleotides, and CRISPR mediated genome editing approaches as new therapeutic strategies. We discuss the significant challenges of translating these promising therapies from the preclinical stage to the clinic, especially for genome editing based approaches.


Tryptase mediates hyperresponsiveness in isolated guinea pig bronchi.
Hyperresponsiveness of airway smooth muscle to allergens and environmental factors has long been associated with the pathophysiology of asthma. Tryptase, a serine protease of lung mast cells, has been implicated as one of the mediators involved in the induction of hyperresponsiveness. As a consequence, tryptase inhibitors have become the subject of study as potential novel therapeutic agents for asthma. Secretory leukocyte protease inhibitor (SLPI) is a naturally occurring protein of human airways which exhibits anti-tryptase activity. To assess the potential therapeutic utility of SLPI in asthma, its effects were evaluated using in vitro and ex vivo models of airway hyperresponsiveness and compared with the effects of the small molecule tryptase inhibitor APC-366. Our results demonstrate that SLPI inhibits tryptase-mediated hyperresponsiveness in vitro and attenuates the hyperresponsiveness observed in airway smooth muscle from antigen-sensitized animals subjected to antigen exposure. The small molecule tryptase inhibitor APC-366 has a similar inhibitory effect. Thus, tryptase appears to be a significant contributor to the development of hyperresponsiveness in these models. To the extent that tryptase contributes to the development and progression of asthma, SLPI may possess therapeutic potential in this disease setting.


Radiofrequency echographic multi-spectrometry and DXA for the evaluation of bone mineral density in a peritoneal dialysis setting.
The aim of this real-life cross-sectional explorative study was to compare radiofrequency echographic multi-spectrometry (REMS) with dual-energy X-rays absorptiometry (DXA) in the BMD assessment of patients receiving peritoneal dialysis (PD). Furthermore, we investigated the relationship between lumbar aortic calcifications (AOCs) and the DXA lumbar measurements. Consecutive patients referring to the PD clinic of our hospital were included. Lumbar spine and femur scans were acquired with both techniques (including lumbar laterolateral DXA scans). The risk assessment of two fracture risk algorithms (FRAX® and DeFRA®) were compared. Cohen's k coefficients were used to assess the inter-technique agreement in the classification of patients as osteoporotic. Lumbar AOCs were estimated semi-quantitatively on laterolateral DXA scans. 41 patients were enrolled. No significant differences were documented between the BMD T-scores measured through DXA or REMS at the femur. At the lumbar spine, the DXA anteroposterior mean T-score (- 0.49 ± 1.98) was significantly higher than both the laterolateral DXA (- 1.66 ± 0.99) and the REMS (- 2.00 ± 1.94) measurements (p < 0.01 vs both). No significant differences were found between the DXA and REMS fracture risk estimates with both algorithms. The inter-technique Cohen's k coefficient (for the worst T-score, any site) was 0.421, p < 0.001. The discrepancy between the DXA laterolateral and anteroposterior lumbar T-score was positively associated with the AOCs extent and severity (r = 0.402, p < 0.01). Our data showed a promising agreement, in a real-life PD setting, between DXA and REMS BMD assessment and in the consequent fracture risk estimation and confirm the AOCs interference on the diagnostic accuracy of lumbar DXA.


Development of a duplex recombinase-aided amplification assay for direct detection of Mycoplasma pneumoniae and Chlamydia trachomatis in clinical samples.
Pneumonia caused by Mycoplasma pneumoniae is common in the elderly and children, and pneumonia caused by Chlamydia trachomatis is prevalent in newborns. This study aimed to establish a rapid, sensitive, and simple method for the direct detection of M. pneumoniae and C. trachomatis in clinical samples without DNA extraction. We established a duplex recombinase-aided amplification (RAA) assay with the RNAseP gene as an internal control for detecting the P1 gene of M. pneumoniae and the ORF8 gene of C. trachomatis, respectively. The results were obtained at 39 °C within 15-20 min. A total of 130 clinical samples suspected of M. pneumoniae or C. trachomatis infection were collected and tested by duplex RAA and PCR. DNA extracted via a commercial kit or treated with a nucleic acid-releasing agent was used and compared, respectively. Standard recombinant plasmids were used to test the sensitivity of the duplex RAA assay. In addition, other similar common pathogens were used to verify the specificity of the duplex RAA assay. The sensitivity of the duplex RAA assay for detecting M. pneumoniae and C. trachomatis was 10 copies/μL using recombinant plasmids. Compared with PCR, the sensitivity and specificity of duplex RAA assays for M. pneumoniae and C. trachomatis was 100% using clinical DNA samples extracted using a commercial kit and a nucleic acid-releasing agent, and the Kappa value was 1. The advantages of this duplex RAA assay include high sensitivity and specificity, short duration, and simple extraction steps, with potential for use in the on-site detection of M. pneumoniae and C. trachomatis in resource-limited settings.


A Central role for mTOR in lipid homeostasis.
The mechanistic target of rapamycin (mTOR) signaling pathway regulates many fundamental metabolic and physiological processes, including lipid metabolism. We explore recent findings on the role of mTOR in lipid homeostasis, with an emphasis on recent findings from in vivo models regarding the role of mTORC2 in lipolysis, lipogenesis, and adipogenesis.


Experimental infection of brushtail possums (Trichosurus vulpecula) with Mycobacterium bovis by conjunctival instillation.
In New Zealand, the brushtail possum (Trichosurus vulpecula) is the major wildlife reservoir of Mycobacterium bovis. Procedures for experimentally infecting possums are required to study the pathogenesis of the disease and to challenge possums in vaccine efficacy studies. Conjunctival instillation of a suspension of M. bovis was effective in producing bovine tuberculosis in captive possums. The experimental disease progressed slowly with the development of palpable lesions in superficial lymph node lesions, both characteristics of the disease in wild, naturally infected possums. At necropsy there was widespread distribution of macroscopic and microscopic lesions. The proportion of possums that became diseased, the rate of development and severity of lesions, the severity of clinical signs, all increased when the dose of M. bovis was increased. Of the three doses used, the medium dose (1000-2000 colony forming units) produced the disease with the most desired characteristics. As a procedure for exposing possums to infection with M. bovis the conjunctival route has advantages in that it is simple and safe to perform, and possums need only to be sedated for infection.


The role of ATP and divalent cations in the regulation of a cardiac phosphorylase phosphatase (phosphoprotein phosphatase) of Mr = 35,000.
The effects of ATP and divalent cations on a divalent cation-independent phosphorylase phosphatase of Mr = 35,000 (phosphatase S) purified from canine cardiac muscle have been studied. The enzyme can be rapidly inactivated by ATP or other nucleoside di- and triphosphates and PPi, but not by AMP, adenosine, adenine, Pi, EDTA, ethylene glycol bis(beta-aminoethyl ether)N,N' -tetraacetic acid, 1,10-phenanthroline, or 8-hydroxyquinoline. After removing the inactivating agent, such as ATP or PPi, by gel filtraiton followed by exhaustive dialysis, the inactivated enzyme (apophosphatase S) can be reactivated by preincubating with Mn2+ or Co2+, but not with Mg2+, Ca2+, Ni2+, Zn2+, Fe2+, Cu2+, Ba2+, Hg2+, Pb2+, or Cd2+. The Mn2+ -reactivated enzyme, which is less active than the Co2+ -reactivated enzyme, can be again inactivated by preincubating with ATP. The present findings indicate that phosphatase S contains a tightly bound divalent cation, probably Mn2+, in the active site. ATP and PPi, due to their structural similarity to the phosphoprotein substrate and their ability to chelate metal ions, can readily enter the active site to remove the divalent cation(s) essential for the catalytic function. The present findings also indicate that phosphatase S, a common catalytic subunit of several larger molecular forms of nospecific phosphoprotein phosphatase in cardiac muscle, can exist in two interconvertible forms, a metallized form (active) and a demetallized form (inactive). ATP and metal ions may regulate this class of isozymes by mediating the interconversions.


Inhalation toxicity of copper compounds: Results of 14-day range finding study for copper sulphate pentahydrate and dicopper oxide and 28-day subacute inhalation exposure of dicopper oxide in rats.
Inhalation exposure to copper may occur during a range of occupational activities and the purpose of this study was to characterise the toxicological response to repeated inhalation of two copper compounds, representative of copper substances in large-scale production/use. Crl:CD(SD) rats were repeatedly exposed to aerosols of dicopper oxide (Cu2O) or copper sulphate pentahydrate (CuSO4.5 H2O) for 14-days as part of a range finding study at normalised copper doses of 0.18, 0.71, 1.78 and 8.9 mg/m3 Cu. Within a 28-days main study (Cu2O only), animals were repeatedly exposed to 0.2, 0.4, 0.8 and 2.0 mg/m3 Cu2O following OECD TG 412. The main study also consisted of satellite groups exposed for 1-, 2- or 3- weeks as well as a 13-week post-exposure recovery period group. Repeated exposure for 14-days to both copper compounds, normalised for copper content, led to an acute influx of polymorphonuclear leukocytes (neutrophils) and macrophages whilst only CuSO4.5 H2O exposure resulted in epithelial hyperplasia. This differential response may reflect the highly dissolvable nature of CuSO4.5 H2O in lung lining fluid leading to a release of copper ions at the epithelial surface whilst Cu2O is relatively indissolvable at neutral pH. In the 28-day study with Cu2O, an increase in cellularity was also evident in both histological and BALF samples and was dose-related with minimal to mild (neutrophilic) inflammation observed > 0.4 mg/m3 in the lung tissue sections and significant increases from 0.2 mg/m3 in BALF. There were no minimal haematological findings, no clinical findings and systemic organs were unaffected by inhalation exposure to dicopper oxide. The lung cellular response was limited to alveolar histiocytosis and neutrophil influx with no evidence of epithelial hyperplasia or fibrosis and all lung biomarkers returned to control levels within the post-exposure recovery period. Interestingly, the satellite groups showed that this acute cellular response followed a biphasic rather than monotonic pattern with a peak in lung biomarkers between weeks 1-3 and reduction thereafter. This reduction in lung biomarkers occurred during continued exposure and may indicate an adaptive response to copper exposure. Overall, these results show that repeated exposure to copper compounds results in an acute cellular response with no associated pathology and which fully resolved after the cessation of exposure. Therefore, the cellular response is evidence of a controlled and adaptive response associated with the removal of Cu2O from the alveolar surface.


Specific drug binding to rat liver cytochrome P-450 isozymes induced by pregnenolone-16 alpha-carbonitrile and macrolide antibiotics. Implications for drug interactions.
Clinical interactions of macrolides with various drugs lead to elimination impairment, increase of plasma concentration and overdose-like effects, resulting from modifications of their metabolism. Previous studies have shown that treatment of rats by the macrolide antibiotics of the oleandomycin and erythromycin series lead to the induction of an hepatic cytochrome P-450 which is implicated into their own metabolism. We have characterized PCN or macrolides induced cytochromes P-450 by their specific ability to interact with macrolide derivatives and, using the cytochrome P-450 spectral binding assays, we have shown that some compounds, implicated in drug interaction with macrolides, interact preferentially with the same cytochromes. This strongly suggests that specific blockage of cytochrome P-450 IIIA1 family by macrolides, is responsible for these drug interactions and that these interactions can be predicted easily by simple in vitro tests such as those described herein.


New targeting strategies in drug therapy of inflammatory bowel disease: mechanistic approaches and opportunities.
Inflammatory bowel disease (IBD) is an exceptional scenario with regard to drug targeting, as oral administration has the potential to deliver the drug directly to the site(s) of action. Consequently, retention of the drug within the intestinal lumen and tissue, rather than systemic absorption, is frequently desirable. In this article, the traditional drug-delivery strategies used in IBD are briefly summarized. These include rectal dosage forms and oral systems that target the lower intestine/colon by pH-, time-, microflora-, and pressure-dependent mechanisms. Then, the article offers an updated overview of recently developed delivery systems aimed to achieve maximal drug concentrations in the inflamed intestinal tissues with minimal systemic side effects. These include antibodies, small molecules, Janus kinase inhibitors, particulate carrier systems, anti-inflammatory peptides, gene therapy, and transgenic bacteria. The various approaches are reviewed, and the challenges that still remain to be overcome are discussed. The molecular revolution of the past decade profoundly influenced the treatment and management of IBD. In the coming years, this trend is expected to continue. Yet, many challenges are still ahead. A strong collaborative effort by experts from different fields is encouraged and necessary to maximize our success in IBD drug targeting.


Development and validation of a high-performance liquid chromatography tandem mass spectrometry assay for atorvastatin, ortho-hydroxy atorvastatin, and para-hydroxy atorvastatin in human, dog, and rat plasma.
A liquid chromatographic/mass spectrometric method to quantitate atorvastatin (AT) and its active metabolites ortho-hydroxy (o-AT) and para-hydroxy (p-AT) atorvastatin in human, dog, and rat plasma was validated. The method consisted of washing plasma samples at high pH with diethyl ether and subsequently extracting the analytes and two internal standards, [d5]-atorvastatin ([d5]-AT) and [d5]-ortho-hydroxy atorvastatin ([d5]-o-AT), from acidified plasma by using diethyl ether. The ether layer was evaporated to dryness and the residue reconstituted in ammonium acetate (20 mM, pH 4.0)-acetonitrile-isopropanol (60:40:1, v/v/v). Chromatographic separation of analytes was achieved by using a YMC J'Sphere H80 (C-18) 150 x 2 mm, 4 microns particle size, column with a mobile phase consisting of acetonitrile-0.1% acetic acid, (70:30, v/v). Analytes were detected by using MS/MS. Sample introduction and ionization was by electrospray ionization in the positive ion mode. The method proved suitable for routine quantitation of AT, o-AT, and p-AT over the concentration range of 0.250 to 25.0 ng/mL. Approximate retention time ranges of p-AT, o-AT, [d5]-o-AT, AT, and [d5]-AT were 2.27 +/- 0.21, 3.36 +/- 0.23, 3.54 +/- 0.46, 4.12 +/- 0.61, and 4.65 +/- 0.65 min, respectively. No peaks interfering with quantitation were observed throughout the validation processes. Mean recoveries of AT, o-AT, and p-AT from plasma ranged 100%-107%, 70.6%-104%, and 47.6%-85.6%, respectively. Mean recoveries of the [d5]-AT and [d5]-o-AT internal standards ranged 98.0%-99.9% and 97.3%, respectively. Interassay precision, based on the percent relative deviation for replicate quality controls for AT, o-AT, and p-AT, was < or = 7.19%, 8.28%, and 12.7%, respectively. Interassay accuracy for AT, o-AT, and p-AT was +/- 10.6%, 5.86%, and 15.8%, respectively. AT, o-AT, and p-AT in human, dog, and rat plasma quality controls were stable to three freeze-thaw cycles. AT, o-AT, and p-AT were stable frozen for 127, 30 and 270 days in human, dog, and rat plasma quality control samples, respectively. Human plasma quality control samples containing AT, o-AT, and p-AT were stable for at least 4 days at ambient room temperature and 37 degrees C. The lower limit of quantitation for all analytes was 0.250 ng/mL for a 1.0-mL sample aliquot.


Pharmacological evidence for the bone-autonomous contribution of the NFκB/β-catenin axis to breast cancer related osteolysis.
The NFκB signaling pathway is implicated in breast cancer and bone metastasis. However, the bone-autonomous contribution of NFκB to breast cancer-induced osteolysis is poorly understood. Here, we report that pretreatment of osteoblasts with the sesquiterpene lactone Parthenolide (PTN), a verified NFκB inhibitor, prior to exposure to conditioned medium from human and mouse breast cancer cell lines enhanced osteoblast differentiation and reduced osteoblast ability to stimulate osteoclastogenesis. PTN prevented breast cancer-induced osteoclast formation and reduced the ability of breast cancer cells to prolong osteoclast survival and to inhibit osteoclast apoptosis. In vivo, administration of PTN in immuno-competent mice reduced osteolytic bone loss and skeletal tumour growth following injection of the syngeneic 4T1-BT1 cells and reduced local osteolysis caused by conditioned medium from human and mouse osteotropic breast cancer cell lines. Mechanistic studies revealed that NFκB inhibition by PTN in osteoblasts and osteoclasts was accompanied by a significant increase in β-catenin activation and expression. Collectively, these results raise the possibility that combined targeting of NFκB and β-catenin signalling in the tumour microenvironment may be of value in the treatment of breast cancer related osteolysis.


Uridine supplementation exerts anti-inflammatory and anti-fibrotic effects in an animal model of pulmonary fibrosis.
Pulmonary fibrosis is a progressive disease with only few treatment options available at the moment. Recently, the nucleoside uridine has been shown to exert anti-inflammatory effects in different animal models, e.g. in acute lung injury or bronchial asthma. Therefore, we investigated the influence of uridine supplementation on inflammation and fibrosis in the classical bleomycin model. Male C57BL/6 mice received an intratracheal injection of bleomycin on day 0 and were treated intraperitoneally with uridine or vehicle. The degree of inflammation and fibrosis was assessed at different time points. Uridine administration resulted in attenuated inflammation, as demonstrated by reduced leukocytes and pro-inflammatory cytokines in the broncho-alveolar lavage (BAL) fluid. Furthermore, collagen deposition in the lung interstitium was also reduced by uridine supplementation. Similar results were obtained in a model in which animals received repeated intraperitoneal bleomycin injections. In addition uridine inhibited collagen and TGF-ß synthesis by primary lung fibroblasts, the release of pro-inflammatory cytokines by human lung epithelial cells, as well as the production of reactive oxygen species by human neutrophils. In summary, we were able to show that uridine has potent anti-inflammatory and anti-fibrotic properties. As uridine supplementation has been shown to be well tolerated and safe in humans, this might be a new therapeutic approach for the treatment of fibrotic lung diseases.


Relative diagnostic value of serum non-SHBG-bound testosterone, free androgen index and free testosterone in the assessment of mild to moderate hirsutism.
Recent evidence suggests that steroid hormone loosely bound to albumin is available for target-cell entry. Preliminary studies have suggested that a measure of this fraction, non-sex-hormone-binding globulin-bound testosterone (NSB-T), provides the best in vitro diagnostic test for idiopathic hirsutism. We compared the diagnostic value of NSB-T, total testosterone (T), free testosterone (fT), and the free androgen index (FAI) in supporting the clinical diagnosis in 22 pre-menopausal women with hirsutism. NSB-T supported the diagnosis in 50% of cases, compared with 23% for T, 55% for fT by analogue RIA, and 68% for FAI. We conclude that in mild to moderate hirsutism the measurement of NSB-T does not yield diagnostic information addition to that provided by the FAI.


Evaluating the EU's Efforts to Improve Resilience to Health and Environmental Risks Associated with Pesticide Use by Analyzing the National Action Plans of EU Member States from 2009 to 2019.
The 2009 "pesticide package" changed the European Union's approach to increasing its resilience to synthetic pesticides' detrimental effects and health risks. It promoted the common goals of reducing volumes, reducing treatment frequency, improving efficacy, reducing risks of pesticide usage, reducing impact, reducing pesticide use in specific areas, and increasing public knowledge and awareness of plant protection products (PPP) usage and effects. Part of the "pesticide package," Directive 2009/128/EC demanded that each EU MS crystalize by 2012 their approach to these goals in National Action Plans (NAPs) designed to systematically assess the situation and propose objectives and measures to achieve the Directive's aims. This article presents a dynamic analysis of the changes that took place between the first (by 2012) and second (by 2019) generation of NAPs and evaluates in measures and a timetable the observed progress in achieving the first goal of Directive 2009/128/EC We assess how the EU MS approach to minimizing risks to public health has changed in this intrinsically environmental policy. We show that improvements-proposing measures designed to achieve the Directive's first goal in all EU MS can be observed, but increasing coherence in measures, timetables, and indicators is needed to accomplish the SUD and EU Green Deal goals.


Perinatal outcomes following bariatric surgery between a first and second pregnancy: a population data linkage study.
To describe the population of women having bariatric surgery and compare the pregnancy outcomes for women having bariatric surgery with a non-bariatric surgery population having a first and second pregnancy. Population-based record linkage study. New South Wales (NSW), Australia. All women aged 15-45 years with a hospital record in NSW (2002-2014) and all women giving birth in NSW (1994-2015; n = 1 606 737 women). Pregnancy and birth outcomes were compared between first and second pregnancies using repeated-measures logistic regression and paired Student's t-tests. Bariatric and non-bariatric groups were also compared. Maternal diabetes, preterm birth (<37 weeks of gestation) and large for gestational age. There was a 13-fold increase in hospitalisations for primary bariatric surgery during 2002-2014. Compared with the general birthing population, women who had bariatric surgery experienced higher rates of hypertension, diabetes, and preterm birth. Among women who had bariatric surgery between a first and second pregnancy, there were reduced rates of hypertension (OR 0.39, 95% CI 0.29-0.53), spontaneous preterm birth (OR 0.37, 95% CI 0.16-0.86), infants that were large for gestational age (OR 0.63, 95% CI 0.44-0.88), and the admission of infants to a special care nursery or neonatal intensive care (OR 0.64, 95% CI 0.46-0.90) in the second pregnancy. Rates for small-for-gestational age and gestational diabetes following surgery were 8.3 and 11.4%, respectively CONCLUSIONS: Bariatric surgery between a first and second pregnancy was associated with reductions in obesity-related adverse pregnancy outcomes. Bariatric surgery performed for the management of obesity in accordance with current clinical criteria is associated with improved pregnancy outcomes in a subsequent pregnancy. Bariatric surgery for obesity may improve pregnancy and birth outcomes in a subsequent pregnancy.


Efficacy of Saudi propolis and bee pollen in the reduction of oxidative stress induced with CCl4 in a testis mice model.
Low testosterone levels are caused by alcoholism, cigarette smoking, and exposure to toxic chemicals. This work focused on investigating the activities of propolis (PE) and bee pollen (BPE) extracts in reducing the oxidative stress of carbon tetrachloride (CCl4) in male mice models. The 48 male Swiss Albino mice weighed 27.5 ± 2.5 g and were divided into: Group1: Control (-) received distilled water only through oral intubation; Group 2: Control (- -) received corn oil by intraperitoneal (i.p.) injection once a day; Group 3: Control (+) received a sublethal dose of CCL4 intraperitoneally the end of the experiment. Group 4: Stander treated with silymarin at a daily dose of 200 mg/kg orally. Group 5: The mice were given 8.4 mg/ kg bw of (PE) orally. Group 6: The mice were given (BPE) extract (140 mg/kg bw) orally. After five consecutive days of treatment, all mice had testis injury in all groups except G1& G2, by a single i.p injection of CCL4 at a dose of 0.5 mL/kg (bw; 20% v/v in corn oil). The result showed a significant increase in luteinizing, follicle-stimulating, and testosterone hormone levels in the serum and semen parameters in the groups treated with PE and BPE. The histological results showed the greatest improvements in testis structures in the BPE group, which was confirmed using (Bcl-2; immunohistochemistry). These results suggest an important role of the antioxidative effects of PE and BPE in the attenuation of CCl4 oxidative stress.


Reassessment of benefit-risk ratio and treatment algorithms for antiarrhythmic drug therapy after the cardiac arrhythmia suppression trial.
The Cardiac Arrhythmia Suppression Trial (CAST) has led to serious reconsideration of both the benefit-risk ratio of antiarrhythmic drug therapy and the appropriate therapeutic approach to various cardiac arrhythmias. Class IC drugs, such as encainide and flecainide, should not be used to treat asymptomatic postinfarction arrhythmias. Furthermore, because the CAST raises serious questions about the concept of treating asymptomatic but "potentially malignant" (prognostically important) arrhythmias guided by ambulatory monitoring, the prophylactic use of any of the antiarrhythmic agents (except beta blockers) must be considered inappropriate and potentially harmful until otherwise established by specific clinical trials. For prophylaxis of malignant ventricular arrhythmias (sustained ventricular tachycardia or ventricular fibrillation), treatment may still begin with standard agents in classes IA, IB, or both, preferably guided by electrophysiologic testing alone or in combination with noninvasive testing. Class IC therapy may be most useful in those patients in this group who do not have such high-risk characteristics for proarrhythmia as a history of multiple myocardial infarctions (MIs), congestive heart failure, or low ejection fraction. Amiodarone is moderately effective for treating these arrhythmias but is reserved as second- or third-line therapy because of its potential organ toxicity. Sotalol, a beta blocker with class III activity, is often effective and relatively well tolerated in these patients and may become a preferred drug when approved. For symptomatic but nonmalignant ventricular arrhythmias, a more conservative approach is more appropriate than in the past, with therapy reversed for those with debilitating symptoms. An initial trial of beta blockade is often appropriate before class I agents are considered.(ABSTRACT TRUNCATED AT 250 WORDS)


The GFP thermal shift assay for screening ligand and lipid interactions to solute carrier transporters.
Solute carrier (SLC) transporters represent the second-largest fraction of the membrane proteome after G-protein-coupled receptors, but have been underutilized as drug targets and the function of many members of this family is still unknown. They are technically challenging to work with as they are difficult to express and highly dynamic, making them unstable in detergent solution. Many SLCs lack known inhibitors that could be utilized for stabilization. Furthermore, as they bind their physiological substrates with high micromolar to low millimolar affinities, binding and transport assays have proven to be particularly challenging to implement. Previously, we reported a GFP-based method for the overexpression and purification of membrane proteins in Saccharomyces cerevisiae. Here, we extend this expression platform with the GFP thermal shift (GFP-TS) assay, which is a simplified version of fluorescence-detection size-exclusion chromatography that combines the sample versatility of fluorescence-detection size-exclusion chromatography with the high-throughput capability of dye-based thermal shift assays. We demonstrate how GFP-TS can be used for detecting specific ligand interactions of SLC transporter fusions and measuring their affinities in crude detergent-solubilized membranes. We further show how GFP-TS can be employed on purified SLC transporter fusions to screen for specific lipid-protein interactions, which is an important complement to native mass spectrometry approaches that cannot cope easily with crude lipid-mixture preparations. This protocol is simple to perform and can be followed by researchers with a basic background in protein chemistry. Starting with an SLC transporter construct that can be expressed and purified from S. cerevisiae in a well-folded state, this protocol extension can be completed in ~4-5 d.


Intraoperative Use of Ultrasound for Assessing Cam Deformity and Cam Resection.
The use of intraoperative fluoroscopy is standard among hip arthroscopist to evaluate and confirm the adequacy of cam resection in patients with femoroacetabular impingement syndrome. However, given the inherent limitations of fluoroscopy, additional intraoperative imaging, such as ultrasound, should be pursued. We offer a technique to measure alpha angles intraoperatively using ultrasound to determine adequate cam resection.


Bioactive compounds, pharmacological actions and pharmacokinetics of Cupressus sempervirens.
The roles of plants and its products in all forms of life cannot be overemphasized. The medicinal products from plant are phytochemicals, drugs, food supplements, beauty products, etc. In ethnomedicine, leaves, fruits, stem, bark, root and fluids from plants are used in the cure, management and prevention of several diseases. Cupressus sempervirens, sometimes called Italian or Mediterranean cypress, is found in subtropical Asia, North America and eastern Mediterranean region. Pharmacological investigations of Cupressus sempervirens showed biological properties such as aromatherapeutic, antiseptic, astringent, balsamic or anti-inflammatory, astringent, antiperspirant, diuretic and antispasmodic. Chemical analysis of Cupressus sempervirens gives phytochemicals like monoterpenes, diterpenes, flavonoid glycosides and bioflavonoids. The current review highlights interactions, conventional uses and biological actions of Cupressus sempervirens plant and plant products.


Problem based learning as a curricular strategy for medical undergraduates: a tutor's experience.
This article focuses on the experiences and role of a tutor while conducting a problem based learning (PBL) exercise to facilitate the learning of biochemistry and molecular biology. A case presentation of sickle cell anemia was used to frame a module. The objective of this experimental exercise was to assess the suitability and effectiveness of problem based learning in the first year of undergraduate medical course and to practice self-assessment by tutors in this new role of a facilitator of learning through small group discussion. A tutor during such a learning session encouraged the students to apply their reasoning to analyze the problem and to develop self-directed learning skills in acquiring the knowledge appropriate to their perceived needs to work on a problem. The tutors ensured that they apply this knowledge in their work with other similar problems that they would encounter later in life.


8-methoxycaffeine inhibition of Drosophila DNA topoisomerase II.
We have investigated the effect of 8-methoxycaffeine on the interaction between Drosophila DNA topoisomerase II and DNA. We have shown that 8-methoxycaffeine affected the enzyme strand-passing activity by inhibiting decatenation of kinetoplast DNA, and that it interfered with the breakage-reunion reaction by stabilizing a cleavable complex. Treatment of the cleavable complex with protein denaturant resulted in DNA breaks. High resolution mapping of the cleavage sites in the central spacer region of Tetrahymena rDNA revealed that, contrary to what was observed with clinically important DNA topoisomerase II inhibitors, 8-methoxycaffeine did not modify the cleavage pattern observed without the drug.


Validation of targeted sequencing of single-nucleotide polymorphisms for non-invasive prenatal detection of aneuploidy of chromosomes 13, 18, 21, X, and Y.
To assess the performance of cell-free DNA (cfDNA) testing in maternal blood for detection of fetal aneuploidy of chromosomes 13, 18, 21, X, and Y using targeted sequencing of single-nucleotide polymorphisms. Prospective study in 242 singleton pregnancies undergoing chorionic villus sampling at 11 to 13 weeks. Maternal blood was collected before chorionic villus sampling and sent to Natera (San Carlos, CA, USA). cfDNA was isolated from maternal plasma, and targeted multiplex PCR amplification followed by sequencing of 19 488 polymorphic loci covering chromosomes 13, 18, 21, X, and Y was performed. Sequencing data were analyzed using the NATUS algorithm that determines the copy number and calculates a sample-specific accuracy for each of the five chromosomes tested. Laboratory personnel were blinded to fetal karyotype. Results were provided for 229 (94.6%) of the 242 cases. Thirty-two cases were correctly identified as aneuploid, including trisomy 21 [n = 25; sensitivity = 100% (CI: 86.3-100%), specificity = 100% (CI: 98.2-100%)], trisomy 18 (n = 3), trisomy 13 (n = 1), Turner syndrome (n = 2), and triploidy (n = 1), with no false positive or false negative results. Median accuracy was 99.9% (range: 96.0-100%). cfDNA testing in maternal blood using targeted sequencing of polymorphic loci at chromosomes 13, 18, 21, X, and Y holds promise for accurate detection of fetal autosomal trisomies, sex chromosome aneuploidies, and triploidy.


Formaldehyde production promoted by rat nasal cytochrome P-450-dependent monooxygenases with nasal decongestants, essences, solvents, air pollutants, nicotine, and cocaine as substrates.
To identify compounds which might be metabolized to formaldehyde in the nasal cavity, 32 potential substrates for cytochrome P-450-dependent monooxygenases were screened with rat nasal and, for comparison, liver microsomes. Tested substrates included 6 nasal decongestants, cocaine, nicotine, 9 essences, 3 potential air pollutants, and 12 solvents. Each test substrate, with the possible exception of the air pollutants, contained one or more N-methyl, O-methyl, or S-methyl groups. Eighteen of the tested materials were metabolized to produce formaldehyde by nasal microsomes. Five substrates, namely, the solvents HMPA and dimethylaniline, cocaine, and the essences dimethyl anthranilate and p-methoxyacetophenone, were metabolized to produce formaldehyde at rates exceeding 1000 pmol/mg microsomal protein/min by nasal microsomes. Eight substrates, including four nasal decongestants, nicotine, and an extract of diesel exhaust particles, were metabolized to produce formaldehyde at rates of 200 to 1000 pmol/mg microsomal protein/min. Five other substrates were metabolized to formaldehyde at detectable rates. The results indicate that a variety of materials which often come in contact with the nasal mucosa can be metabolized to formaldehyde by nasal enzymes. The released formaldehyde may influence the irritancy of inhaled compounds and has been suggested to play a role in the tumorigenicity of some compounds.


Psychosocial Determinants of COVID-19 Vaccine Hesitancy and the Mediating Role of Various Attitudes towards Science.
This study examined the way attitudes towards science in the U.S. mediate the relationship between COVID-19 vaccine hesitancy and psychosocial predictors, such as political ideology, religiosity, reactance proneness, dogmatism, perceived communal ostracism, education, and socioeconomic status. We analyzed the structure of people's attitudes towards science, revealing four distinct factors: epistemic confidence, belief that science and technology are beneficial, trust in science in general, and trust in medical science. With all four factors included as mediators in a saturated path analysis, low levels of trust in medical science and low epistemic confidence fully mediated the relationships between nearly all of the psychosocial predictors and COVID-19 vaccine hesitancy. Political conservativism's negative association with vaccine hesitancy was partially mediated by the same two facets of people's attitudes towards science. Adding nuance to existing research, we found that trust in science in general was not a significant mediator once all four facets were included in the model. These findings are discussed with a focus on their implications for understanding attitudes towards science and their substantial and complex role in COVID-19 vaccine hesitancy.


Implementation of a Longitudinal Mentorship Program for Quality of Life, Mental Health, and Motivation of Brazilian Medical Students.
Mentoring has been used as a strategy for mental health prevention and the promotion of quality of life in medical students, with mixed results. The aim of this study was to compare the levels of mental health, quality of life, and academic motivation of medical students after implementation of a longitudinal curricular mentoring program relative to those students without mentoring in their curricula. The results of the mentoring program were assessed by comparing two classes of 2nd-year students of a school of medicine (one that had received mentoring since admission and another which had no exposure to the method during the course). Self-report questionnaires were used to collect data on sociodemographics, quality of life (WHOQOL-BREF), mental health (DASS-21), and academic motivation (Academic Motivation Scale-AMS). A total of 95 medical students were included: 55 received the mentoring program and 40 did not receive the program. The Multivariate GLM regression model revealed no significant main effect of mentoring on domains of the WHOQOL-BREF (Wilks's Lambda = 0.938, F = 1.427, p < 0.232); the DASS-21 (Wilks's Lambda = 0.051, p < 0.985); or the AMS (Wilks's Lambda = 0.957, F = 0.628, p < 0.708). Likewise, the Univariate GLM regression showed no significant main effect of mentoring on medical students' perceived health (F = 0.585; d.f. = 1; p = 0.446). Mentoring promoted no significant changes in the students of this Brazilian institution. These results highlight the challenges faced in structuring, maintaining, and assessing an effective mentoring program for students on medicine courses.


Role of unusually long common pancreatico-biliary channel as a cause of relapsing pancreatitis in children.
The article reports on two children with relapsing pancreatitis. In both cases operative cholangiogram demonstrated unusually long common pancreatico-biliary channel not associated with cystic dilatation of the common bile duct. The possibility and hypothetical mechanism that the long common pancreatico-biliary channel caused relapsing pancreatitis, are described. Exploratory laparotomy should be considered for children having recurrent abdominal pain with hyperamylasemia. For surgical treatment of this type of relapsing pancreatitis excision of the common bile duct and the gallbladder with hepatoenterostomy will be the best method.


The effect of big-city news on rural America during the COVID-19 pandemic.
Can "urban-centric" local television news coverage of the COVID-19 pandemic affect the behavior of rural residents with lived experiences so different from their "local" news coverage? Leveraging quasi-random geographic variation in media markets for 771 matched rural counties, we show that rural residents are more likely to practice social distancing if they live in a media market that is more impacted by COVID-19. Individual-level survey responses from residents of these counties confirm county-level behavioral differences and help attribute the differences we identify to differences in local television news coverage-self-reported differences only exist among respondents who prefer watching local news, and there are no differences in media usage or consumption across media markets. Although important for showing the ability of local television news to affect behavior despite urban-rural differences, the media-related effects we identify are at most half the size of the differences related to partisan differences.


A Review of Antipsychotics and Priapism.
Pharmacologically induced priapism is now the most common cause of priapism, with approximately 50% of drug-related priapism being attributed to antipsychotic usage. The majority of pharmacologic priapism is believed to result in ischemic priapism (low flow), which may lead to irreversible complications, such as erectile dysfunction. It is imperative that prescribing physicians be aware of potentially inciting medications. To identify medications, specifically antipsychotics, associated with priapism and prolonged erections and understand the rates and treatment of these side effects. A PubMed search of all articles available on the database relating to priapism, prolonged erections, and antipsychotics was performed. Various typical and atypical antipsychotic drugs (APDs) have been implicated in pharmacologically induced priapism. In addition to dopaminergic and serotoninergic receptors, APDs have affinities for a wide array of other receptors in the central nervous system, including histaminergic, noradrenergic, and cholinergic receptors. Although the exact mechanism is unknown, the most commonly proposed mechanism of priapism associated with APDs is α-adrenergic blockade in the corpora cavernosa of the penis. Priapism appears in only a small fraction of men using medications with α1-receptor-blocking properties, indicating differential sensitivities to the α-blocking effect among men, and/or additional risk factors that may contribute to the development of priapism. The best predictor for the subsequent development of priapism is a past history of having prolonged and painless erections. The acute management algorithm of APD-induced priapism is the same as for other causes of low-flow priapism. Clinicians should educate patients treated with antipsychotics about the potential for priapism and its sequelae including permanent erectile dysfunction. Appropriate patient education will raise awareness, encourage early reporting, and help reduce the long-term consequences associated with priapism through early intervention. Hwang T, Shah T,Sadeghi-NejadH. A Review of Antipsychotics and Priapism. Sex Med Rev 2021;9:464-471.


Revision total hip arthroplasty is associated with significantly higher opioid consumption as compared to primary total hip arthroplasty in the acute postoperative period.
There are currently a lack of investigations that characterised narcotic utilisation following revision total hip arthroplasty (THA). We sought to determine if immediate post-surgical opioid use was different between revision THA and primary THA. A single institution total joint arthroplasty database was used to identify adult patients who underwent revision THA or primary THA from 2016 to 2019. Morphine milligram equivalents (MME) were calculated for different time periods. 6977 patients were identified, 89.72% primary THA and 10.28% revision THA. Aggregate opioid consumption was higher for revision THA patients (317.40 MME vs. 93.01 MME), as was opioid consumption in the first 24 hour and second 24-hour periods. Visual analogue pain (VAS) scores were significantly higher in the 0-12 hour postoperative and the 12-24 hours postoperative periods in the revision THA group. Patients undergoing revision THA had significantly higher narcotic utilisation than those undergoing primary THA, particularly in the first 24 hours postoperatively.


Transcatheter aortic valve replacement in left ventricular assist device patient-overcoming the complications with transapical approach and circulatory arrest.
We present the patient with severe aortic insufficiency (AI) 5 years post left ventricular assist device (LVAD) implantation. His management was complicated with unsuccessful percutaneous aortic valve closure attempt, transcatheter aortic valve replacement (TAVR) implantation with a severe paravalvular leak, eventual valve dislodgment into the left ventricle (LV), and LVAD inflow cannula occlusion. We utilized a mini-thoracotomy approach to successfully retrieve the dislodged valve through the LV apex while deploying a valve-in-valve TAVR under direct visualization and deep hypothermic cardiac arrest. This case can serve as an example of the serious pitfalls and potential resolution strategies when treating LVAD-associated AI.


Lignan and megastigmane glycosides from Sauropus androgynus.
A lignan diglycoside, (-)-isolariciresinol 3alpha-O-beta-apiofuranosyl-(1-->2)-O-beta-glucopyranoside, and a megastigmane glucoside, sauroposide, were isolated from the aerial part of Sauropus androgynus together with (+)-isolariciresinol 3alpha-O-beta-glucopyranoside, (-)-isolariciresinol 3alpha-O-beta-glucopyranoside, (+)-syringaresinol di-O-beta-glucopyranoside, guanosine and corchoionoside C. The structural elucidations were bases on analyses of physical and spectroscopic data.


Ocular adverse effects of human chorionic gonadotropin.
This is the first case report of blurred vision and scotomas associated with hCG injections. Similar visual disturbances have been caused by clomiphene, which is similar to hCG in enhancing LH activity and increasing testosterone levels.


Diagnosis of ocular and glandular toxoplasmosis using the Indian ink immunoreaction.
The Indian ink immunoreaction (IIR) as a method for diagnosis of Toxoplasma infection has been evaluated. 68 sera from patients with suspected ocular and glandular toxoplasmosis and 30 control sera from normal individuals were tested using both indirect fluorescent antibody test (IFAT) and IIR. The test proved to be specific, simple and rapid especially for screening purposes.


Feasibility and safety of continuous retrograde administration of Del Nido cardioplegia: a case series.
Del Nido (DN) cardioplegia, a calcium-free, hyperkalemic solution containing lidocaine and magnesium has been developed to help reduce intracellular calcium influx and the resulting myocyte damage in the immediate postischemic period following cardiac arrest. DN cardioplegia has been used for pediatric cardiac surgery but its use in complex reoperative surgery has not been studied. We specifically report the outcomes of patients undergoing reoperative cardiac surgery after previous coronary artery bypass grafting with a patent internal mammary artery (IMA). Patients undergoing reoperative cardiac surgery with prior coronary bypass grafting surgery were studied between 2010 and 2013. Fourteen patients were identified who required continued retrograde cardioplegia administration. In all cases, an initial antegrade dose was given, followed by continuous retrograde administration. Demographics, co-morbidities, intra-operative variables including cardioplegia volumes, post-operative complications, and patient outcomes were collected. The mean age of all patients was 73.3+/-6.7 years, and 93 % were male. Aortic cross clamp time and cardiopulmonary bypass times were 81+/-35 and 151+/-79 mins, respectively. Antegrade, retrograde and total cardioplegia doses were 1101+/-398, 3096+/-3185 and 4367+/-3751 ml, respectively. An average of 0.93+/-0.92 inotropes and 1.50+/-0.76 pressors were used on ICU admission after surgery. ICU and total hospital lengths of stay were 5.5+/-7.4 and 9.6+/-8.0 days, respectively. Complications occurred in two patients (14 %) (pneumonia and prolonged mechanical ventilation) and new arrhythmias occurred in five patients (36 %) (four new-onset atrial fibrillation and one pulseless electrical activity requiring 2 min of chest compression). No perioperative myocardial infarctions were noted based on electrocardiograms and cardiac serum markers. Postoperatively, left ventricular function was preserved in all patients whereas two patients (14 %) had mild decrease in right ventricular function as assessed by echocardiography. No mortality was observed. Del Nido cardioplegia solution provides acceptable myocardial protection for cardiac surgery that requires continuous retrograde cardioplegia administration. DN cardioplegia's administration in a continuous retrograde fashion with a patent IMA is believed to provide adequate myocardial protection while avoiding injuring the IMA through dissection and clamping.


First-principles quantum dynamical theory for the dissociative chemisorption of H2O on rigid Cu(111).
Despite significant progress made in the past decades, it remains extremely challenging to investigate the dissociative chemisorption dynamics of molecular species on surfaces at a full-dimensional quantum mechanical level, in particular for polyatomic-surface reactions. Here we report, to the best of our knowledge, the first full-dimensional quantum dynamics study for the dissociative chemisorption of H2O on rigid Cu(111) with all the nine molecular degrees of freedom fully coupled, based on an accurate full-dimensional potential energy surface. The full-dimensional quantum mechanical reactivity provides the dynamics features with the highest accuracy, revealing that the excitations in vibrational modes of H2O are more efficacious than increasing the translational energy in promoting the reaction. The enhancement of the excitation in asymmetric stretch is the largest, but that of symmetric stretch becomes comparable at very low energies. The full-dimensional characterization also allows the investigation of the validity of previous reduced-dimensional and approximate dynamical models.


Pharmacology education: a theoretical framework of applied pharmacology and therapeutics.
United Kingdom Government initiatives such as The NHS Plan (DoH 2000) identified the need for nurses to undertake multi-skilled professional roles. In the United Kingdom, the transition to a larger graduate nurse workforce continues, as Universities offer nurse pre-registration courses at diploma and degree levels. Concomitant with the change in educational standard is the need to teach student nurses the theoretical principles of medication management and to develop skills in clinical reasoning skills. Both elements are limited in current educational pre-registration nurse programmes, in order to develop the future, multi-skilled workforce such courses should incorporate the theory and skills of health assessment, physical examination, applied pharmacology and clinical reasoning. This paper aims to examine how knowledge of applied pharmacology and therapeutics can be integrated into an undergraduate pre-registration nursing programme. Discussion focuses on how this generic framework can provide educators with an outline of the theoretical constructs, their application, the teaching strategies involved and instruction on how to prepare nurses to clinically reason with regard to medication management issues. This framework can be adapted to accommodate nurses studying for all parts of the register.


Knee flexors/extensors in gait of elderly and young able-bodied men (II).
In this study the fundamental tasks of muscle activity at the knee during gait in elderly and young able-bodied subjects were identified using principal component analysis (PCA). Role discrepancies between the older and younger subjects for the actions executed by the knee flexors and extensors during the gait cycle were also investigated. The t-test for independent groups was applied to determine significant differences between spatio-temporal and peak muscle moment parameters (P<0.05). PCA as a multivariate classification and curve structure detection method was applied to the sagittal knee muscle moment curves of twenty elderly (72 +/-5.5 years) and twenty young (25 +/- 8.1 years) subjects. The first three principal components (PCs) which accounted for 80% (older) and 93% (younger) of the information were retained for further analysis. Providing stable locomotion was recognised as a major task of the knee in the older subjects, while for the younger subjects the knee contributed to both balance and propulsion. Supporting the body during single limb support should be considered the only common task at the knee level in elderly and young subjects' gait. The lack of muscle power for propulsion might be the reason for not identifying the knee extensor muscle roles in the first three major tasks during elderly gait. Functional asymmetry can be considered the result of a different ordering of the functional roles of the muscles acting at the knee level in elderly and young subjects.


Expression, crystallization and preliminary X-ray analysis of extracellular modules of the neural cell-adhesion molecules NCAM and L1.
Recombinant proteins consisting of either the four or five amino-terminal immunoglobulin (Ig) modules of the rat neural cell-adhesion molecule NCAM or the whole extracellular part [six Ig and five fibronectin type III (F3) modules] of mouse L1 have been expressed in Drosophila S2 cells. The proteins have been purified and crystallized. The crystals of the recombinant protein containing the four amino-terminal Ig modules of NCAM diffract X-rays to approximately 4 A resolution and belong to space group P622 or P6(3)22, with unit-cell parameters a = b = 258.7, c = 182.4 A. No diffraction was observed for the other two protein constructs. This is a step towards determining the structure of multimodular constructs of cell-adhesion molecules that exhibit high structural flexibility.


Marginal leakage in direct and indirect composite resin restorations in primary teeth: an in vitro study.
The aim of this study was to evaluate the marginal leakage in class II preparations, with margins in enamel, restored with composite resin indirect and direct restorations. Twenty extracted primary molars were chosen and divided at random into two groups: G1 (n=10) restored by a direct technique and G2 (n=10) restored by an indirect technique. The composite resin Filtek Z250 (3M) and the Adper Single Bond adhesive (3M) were used in both groups. Teeth were stored in a humid environment at 37 degrees C for 1 week, thermo cycled (500 cycles, 5 degrees C and 55 degrees C), sealed and immersed in a 0.5% basic fuchsine dye for 24h. Teeth were longitudinally sectioned, in a mesio-distal direction and leakage was assessed. No leakage in the specimens from G2 and leakage in four specimens from G1, but the Mann-Whitney test showed that there was no statistically significant difference between the groups, either for occlusal box (p=0.317) and proximal box (p=0.067). This study demonstrated that direct and indirect class II composite resin restorations with cervical margins in enamel show similar results regarding marginal leakage.