Adrenal myelolipoma presenting with spontaneous retroperitoneal haemorrhage demonstrated on computed tomography and angiogram--a case report.
A rare case of adrenal myelolipoma presenting with spontaneous rupture and retroperitoneal haemorrhage is described. A 51-year-old Caucasian male presented with acute onset of right loin pain. Preliminary diagnosis of haemorrhagic adrenal tumour was made on computed tomography (CT) and angiography. Vascular embolisation was performed to stabilise the patient prior to definitive surgery. Tumour resection was subsequently performed. Histology confirmed ruptured adrenal myelolipoma. The patient made an uneventful recovery. Ruptured adrenal myelolipoma should be considered in cases of spontaneous retroperitoneal haemorrhage. Vascular embolisation may be useful in stabilising the patient prior to definitive surgery.


An optimized two-finger archive for ZFN-mediated gene targeting.
The widespread use of zinc-finger nucleases (ZFNs) for genome engineering is hampered by the fact that only a subset of sequences can be efficiently recognized using published finger archives. We describe a set of validated two-finger modules that complement existing finger archives and expand the range of ZFN-accessible sequences threefold. Using this archive, we introduced lesions at 9 of 11 target sites in the zebrafish genome.


Response of cultured endothelial cells to mechanical stimulation.
Endothelial cells covering the luminal surface of vessels are exposed to at least two different mechanical forces: 1) fluid shear stress produced by the circulation of blood, and 2) periodic stretching and relaxing as a result of the diameter oscillations caused by blood pulsation. In this study we present an apparatus which was constructed to imitate the volume pulse with its typical incisura of the abdominal aorta. Using this apparatus, we exposed cultured endothelial cells to continuously produced cyclic and directional stretching and relaxation for three days. In all experiments cells remained attached and viable when subjected to mechanical stimulation. The vast majority of endothelial cells which underwent mechanical stimulation became elongated and oriented with their longer axis perpendicular to the direction of stretching (angle of cell orientation: alpha = 88.7 degrees +/- 12 degrees; means +/- SD), whereas cells on unstretched membranes had a cobblestone-like appearance and remained in random orientation. In the stretched cells, the factor of elongation was f = 6.8 +/- 1.3; means +/- SD; unstretched cells which exhibited a polygonal shape had a factor of elongation of f = 1.8 +/- 0.8; means +/- SD. In addition, the behavior of cytoskeletal components such as microfilaments and microtubules was examined in the process of cell orientation as both are actively involved in alterations of cell shape and cell migration. Actin filaments were oriented as both are actively involved in alterations of cell shape and cell migration. Actin filaments were oriented in parallel alignment perpendicular to the stretch direction (angle of actin filament orientation: beta = 90.4 degrees +/- 9 degrees; means +/- SD). A distinct orientation of microtubules was not observed, although a noticeable number of microtubules was observed to be in parallel alignment. Furthermore, microtubules of cells which underwent mechanical stimulation exhibited a pronounced asymmetric intracellular distribution with strongly fluorescent cytoplasmic areas in which microtubules seemed to be accumulated. The results indicate that endothelial cell elongation and orientation in vitro can be induced by periodic stretching and relaxation comparable to the periodic oscillations of the vessel wall due to blood pulsation in vivo.


Effects of irrigation water salinity on evapotranspiration modified by leaching fractions in hot pepper plants.
We investigated whether leaching fraction (LF) is able to modify the effects of irrigation water salinity (ECiw) on evapotranspiration (ET). We conducted an experiment with a completely randomized block design using five levels of ECiw and two LFs. Results showed that the electrical conductivity of drainage water (ECdw) in an LF of 0.29 was considerably higher during the 21-36 days after transplanting (DAT), and considerably lower after 50 DAT than in an LF of 0.17. The hourly, nighttime, daily, cumulative and seasonal ET all decreased considerably as a result of an increase in the ECiw. The daily ET started to be considerably higher in the LF of 0.29 than in the LF of 0.17 from 65 DAT. Compared with the LF of 0.17, the seasonal ET in the LF of 0.29 under various ECiw levels increased by 4.8%-8.7%. The Maas and Hoffman and van Genuchten and Hoffman models both corresponded well with the measured relative seasonal ET and the LF had no marked effects on these model parameters. Collectively, an increase in the level of ECiw always decreased the ET substantially. An increase in the LF increased the ET considerably, but there was a time lag.


Can Healing Architecture Increase Safety in the Design of Psychiatric Wards?
The objective of this discussion paper is to deepen the discourse on the complex interrelationship between "healing architecture" and "safe architecture," here labeled "The healing and safety complex," for the benefit of those who want to make informed decisions in the design of future psychiatric wards. Today's psychiatric care sets the patient at the forefront. As a part of this ambition, the discussion regarding the patient's physical environment has also advanced. At the same time, staff are exposed to increasing threats and violence in their everyday work, which can lead to severe personal psychological suffering as well as physical injuries. The requirements of patients and staff are sometimes conflicting which has ethical implications. The reasoning and arguments presented here mainly derive from discussions and dialogue with psychiatric facility management and other healthcare professionals in multidisciplinary working groups during the design process. Offering patients and staff a healing and safe environment is the most important architectural challenge in the design of psychiatric wards. How architects, management, and staff evaluate and balance the two aspects will have a crucial impact on the building's final design and atmosphere and thereby influence staff and patient safety as well as civil protection. In everyday practice, it is up to the multidisciplinary design teams and management to become better informed in order to make "the right decisions to the best of their ability" as evidence is still limited when it comes to "The healing and safety complex."


Continuous oxygen monitoring of the conjunctiva in neonates.
To report the first use of a noninvasive conjunctival oxygen monitor in neonates. We wished to investigate if measuring the partial pressure of oxygen directly from the conjunctiva could track hyperoxia and hypoxia as well as, or better than, pulse oximetry. This has the potential to reflect brain oxygenation while yielding important systemic information. Criteria standard. Tertiary care hospital neonatal intensive care unit. Ten newborns monitored with pulse oximetry. The conjunctival oxygen monitor was studied for effectiveness and safety and compared to pulse oximetry. The device remained on the eyes up to 120 minutes. The correlation coefficient between conjunctival oxygen tension and pulse oximetry was significant for all readings (p<0.001) and for pulse oximetry measurements below 100% (p=0.024). One infant developed eyelid edema, which subsided when the device was removed and one sustained a small corneal abrasion that healed overnight. This initial pilot report suggests that the conjunctival oxygen monitor is effective and relatively safe in neonates. The device holds promise to indicate a tissue oxygen reading, which may provide neonatologists with more information about systemic oxygenation.


The Modified Z-Epicanthoplasty-A Stepwise and Individualized Design.
To describe a medial epicanthoplasty technique using a stepwise, customized design and to review the outcome in Asian patients after the treatment of medial epicanthal fold. Retrospective, noncomparative and interventional case series with the introduction of a new surgical technique. Forty-eight consecutive Asian patients with primary medial epicanthal fold. Patient charts were reviewed from patients (mean age, 24.6 ± 3.8 years; range, 19-40 years) with a stepwise z-epicanthoplasty. The intercanthal distance (ICD), interpupillary distance (IPD), and scar visibility were evaluated at regular intervals (preoperative, immediate postoperative, 3 months, 6 months, and 1 year after the operation). The ratio of the ICD to IPD (ICD ratio) was calculated, and the visibility of the surgical scar assessed. Postoperative improvement in ICD ratio and scar quality. The preoperative median ICD ratio was 0.60 (range, 0.57-0.66) and decreased to 0.57 (range, 0.52-0.60) postoperatively. The median ICD ratio reduction was 5.6% (range, 2.6-14.1%; P < 0.001, Wilcoxon signed-rank test). Forty patients (83.3%) had no visible scarring or scarring only visible under close inspection. Eight patients (16.7%) experienced a more apparent scar, but none of them developed a severe scar requiring revision. The modified z-epicanthoplasty using a stepwise design is a customized and effective technique for the treatment of the epicanthal fold. This method has a short learning curve, is widely applicable to various types of epicanthal fold, and has a high satisfaction rate with a stable long-term result.


Detection of PEGylated proteins in polyacrylamide gels by reverse staining with zinc and imidazole salts.
The reverse staining, with imidazole-SDS-zinc, of PEG-linked proteins separated by SDS-PAGE was studied. Using model conjugates (interferon-alpha 2b (IFN-alpha2b) reacted with either a branched-chain (40,000) PEG (PEG2,40) or a linear monomethoxy PEG polymer (Mr of 12,000) and chromatographically purified monoPEG2,40-IFN-alpha2b), conventional small-format analytical gels (<1 mm thick) showed typical detection patterns (i.e., transparent, colorless bands clearly discernible against a zinc imidazolate-generated white gel background), in less than 20 min. Nonreacted (free) PEG was almost undetected, as expected. The reverse-stained PEGylated IFN-alpha2b patterns were qualitatively indistinguishable from those of parallel gels stained with iodine (I2). The LOD was estimated in the low nanogram range (e.g., at about 7 ng for mono- or bi-PEG2,40 IFN-alpha2b per lane on gradient (4-17%) gels). Also, this stain allowed the visualization of Coomassie blue-undetected PEG-IFN bands, and could be restained with I2. PEGylated species of lysozyme, a low-molecular-weight peptide, ovalbumin, and chymotrypsin were used to demonstrate the generality of this stain. We also show (i) how to counteract the adverse effect of some parameters (e.g., gel thickness above 1 mm, long gel length, low (e.g., 4-6%) acrylamide concentration) on the reverse staining process and (ii) that the properties of the reverse-stained PEGylated proteins remain unchanged, as judged by analyzing both the ion exchange chromatography-based positional isomer separation profile and enzyme-linked immunosorbent response of PEG-IFN recovered from gels. Consequently, this technique may be useful for the rapid analysis or the small-scale preparation of PEGylated proteins.


The Emergency nurse Protocols Initiating Care-Sydney Triage to Admission Risk Tool (EPIC-START) trial: protocol for a stepped wedge implementation trial.
Emergency department (ED) overcrowding is a global problem and a threat to the quality and safety of emergency care. Providing timely and safe emergency care therein is challenging. To address this in New South Wales (NSW), Australia, the Emergency nurse Protocol Initiating Care-Sydney Triage to Admission Risk Tool (EPIC-START) was developed. EPIC-START is a model of care incorporating EPIC protocols, the START patient admission prediction tool, and a clinical deterioration tool to support ED flow, timely care, and patient safety. The aim of this study is to evaluate the impact of EPIC-START implementation across 30 EDs on patient, implementation, and health service outcomes. This study protocol adopts an effectiveness-implementation hybrid design (Med Care 50: 217-226, 2012) and uses a stepped-wedge cluster randomised control trial of EPIC-START, including uptake and sustainability, within 30 EDs across four NSW local health districts spanning rural, regional, and metropolitan settings. Each cluster will be randomised independently of the research team to 1 of 4 dates until all EDs have been exposed to the intervention. Quantitative and qualitative evaluations will be conducted on data from medical records and routinely collected data, and patient, nursing, and medical staff pre- and post-surveys. Ethical approval for the research was received from the Sydney Local Health District Research Ethics Committee (Reference Number 2022/ETH01940) on 14 December 2022. Australian and New Zealand Clinical trial, ACTRN12622001480774p. Registered on 27 October 2022.


Diagnostic Performance of Strain and Shear Wave Elastography for the Response to Neoadjuvant Chemotherapy in Breast Cancer Patients: Systematic Review and Meta-Analysis.
To investigate the diagnostic performance of strain and shear wave elastography for the response to neoadjuvant chemotherapy (NAC) in breast cancer patients. Relevant studies were searched in the databases of PubMed, Web of Science and Cochrane Library until October 2021. The diagnostic performance of ultrasonic elastography for the response to NAC were estimated by calculating the area under the curve (AUC) with sensitivity and specificity using Stata 14.0. A total of 15 studies that comprise 1147 breast cancer patients were included in this meta-analysis. The pooled AUC of strain elastography in diagnosing responses were 0.89 (95% CI = 0.86-0.91) with 87% (95% CI = 75-94%) of sensitivity and 80% (95% CI = 72-84%) of specificity. The pooled AUC of shear wave elastography in diagnosing response were 0.82 (95% CI = 0.78-0.85) with 79% (95% CI = 72-84%) of sensitivity and 81% (95% CI = 71-88%). No publication bias was observed across the studies using Deek's funnel plot. Based on current evidence, this meta-analysis confirmed that strain and shear wave elastography exhibited favorable performance for predicting responses to NAC. Strain and shear wave elastography may be a useful, noninvasive method for the assessment of response to NAC in breast cancer patients.


The genomic and proteomic blueprint of mouse megakaryocytes derived from embryonic stem cells.
Platelets are specialized cells, produced by megakaryocytes (MKs) in the bone marrow, which represent the first defense against hemorrhage. There are many diseases where platelet production or function is impaired, with severe consequences for patients. Therefore, new insights into the process of MK differentiation and platelet formation would have a major impact on both basic and clinical research. Embryonic stem (ES) cells represent a good in vitro model to study the differentiation of MKs, with the possibility of being genetically engineered and constituting an unlimited source of MKs. However, lack of knowledge about the molecular identity of ES-derived MKs (ES-MKs) may prevent any further development and application of this model. This paper presents the first comprehensive transcriptional and proteome profile analyses of mouse ES-MKs in comparison with MKs derived from mouse fetal liver progenitors (FL-MKs). In ES-MKs we found a down-regulation of cytoskeleton proteins, specific transcription factors and membrane receptors at both transcriptional and protein levels. At the phenotypic level, this molecular blueprint was displayed by ES-MKs' lower polyploidy, lower nuclear/cytoplasm ratio and reduced capacity to form proplatelets and releasing platelets. Overall our data demonstrate that ES-MKs represent a useful model to clarify many aspects of both MK physiology and pathological conditions where impaired MK functions are related to defective MK development, as in inherited thrombocytopenias and primary myelofibrosis.


Nitric oxide generated by the compound RuBPY promotes the vascular smooth cell membrane hyperpolarization.
The cis-[Ru(bpy)(2)(py)NO(2)](PF(6)) specie (RuBPY) has been used as nitric oxide (NO) delivery agent. It is an NO reservoir and it is thermodynamically stable in aqueous solution. This study aimed to evaluate the NO specie generated by RuBPY as compared to NO released from sodium nitroprusside (SNP) and to study the cellular mechanisms specially focusing the activation of soluble guanylyl-cyclase (sGC), K(+) channels and the cell membrane hyperpolarization, which are the main targets for NO-inducing vascular relaxation. NO generated by RuBPY and the vascular smooth muscle cell (VSMC) membrane potential were measured by confocal microscopy. The cellular mechanisms of aorta relaxation were investigated using K(+) channel blockers and sGC inhibitor. NO released from RuBPY was higher than NO released from SNP. RuBPY released only radicalar NO(0) and SNP released both NO(-) and NO(0). The concentration-effect curves for RuBPY-induced relaxation was shifted to the right by inhibition of sGC with ODQ and by the non-selective blockade of K(+) channels with TEA. The simultaneous combination of ODQ and TEA abolished the vasorelaxation induced by RuBPY. The membrane potential measured by the sensitive dye 4-Di-ANNEPS demonstrated that RuBPY induces cell membrane hyperpolarization. Taken together, our results indicate that the large amount of NO(0) specie generated by RuBPY induces vasorelaxation due to activation of sGC, K(+) channels sensitive to TEA, and cell membrane hyperpolarization. These results indicate that NO(0) generated from RuBPY can also directly activate the K(+) channels in an independent way of sGC.


Engineering highly thermostable Cas12b via de novo structural analyses for one-pot detection of nucleic acids.
CRISPR-Cas-based diagnostics have the potential to elevate nucleic acid detection. CRISPR-Cas systems can be combined with a pre-amplification step in a one-pot reaction to simplify the workflow and reduce carryover contamination. Here, we report an engineered Cas12b with improved thermostability that falls within the optimal temperature range (60°C-65°C) of reverse transcription-loop-mediated isothermal amplification (RT-LAMP). Using de novo structural analyses, we introduce mutations to wild-type BrCas12b to tighten its hydrophobic cores, thereby enhancing thermostability. The one-pot detection assay utilizing the engineered BrCas12b, called SPLENDID (single-pot LAMP-mediated engineered BrCas12b for nucleic acid detection of infectious diseases), exhibits robust trans-cleavage activity up to 67°C in a one-pot setting. We validate SPLENDID clinically in 80 serum samples for hepatitis C virus (HCV) and 66 saliva samples for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with high specificity and accuracy. We obtain results in as little as 20 min, and with the extraction process, the entire assay can be performed within an hour.


E3 ubiquitin ligase mind bomb 1 overexpression reduces apoptosis and inflammation of cardiac microvascular endothelial cells in coronary microvascular dysfunction.
The apoptosis and inflammation in cardiac microvascular endothelial cells (CMECs) promote the development of coronary microvascular dysfunction (CMD). The present study aimed to explore the role of E3 ubiquitin ligase mind bomb 1 (MIB1) in the apoptosis and inflammation in CMECs during CMD. In vivo, CMD in rats was induced by sodium laurate injection. In vitro, rat primary CMECs were stimulated by homocysteine (Hcy). The apoptosis of CMECs was measured using flow cytometry. The inflammation of CMECs was evaluated by the level of tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β). The interplay between MIB1 and mitogen-activated protein kinase kinase kinase 5 (map3k5, also called ASK1) was measured using Co-immunoprecipitation. MIB1 expression was decreased and ASK1 expression was increased in the heart tissues of CMD rats and Hcy-treated CMECs. MIB1 overexpression decreased fibrinogen-like protein 2 (FGL2) secretion, inflammation, and apoptosis induced by Hcy in CMECs. Meanwhile, MIB1 overexpression decreased the protein levels of ASK1 and p38, while not affected ASK1 mRNA levels. The following mechanism experiments revealed that MIB1 downregulated ASK1 expression by increasing its ubiquitination. ASK1 overexpression reversed the inhibitory effect of MIB1 on FGL2 secretion, apoptosis, inflammation, and p38 activation in Hcy-treated CMECs. In CMD rats, MIB1 overexpression partly retarded CMD progression, manifesting as increased coronary capillary density and decreased microthrombi formation. MIB1 overexpression relieved apoptosis and inflammation of CMECs during CMD by targeting the ASK1/p38 pathway.


Effects of free fat grafting on the prevention of Frey's syndrome and facial depression after parotidectomy: A prospective randomized trial.
To evaluate the effectiveness of free fat grafting in preventing Frey's syndrome (FS) and facial depression after parotidectomy compared with acellular dermis. A prospective randomized trial was performed. Patients who underwent parotidectomy were randomly assigned to abdominal free fat or acellular dermis grafting groups. The occurrence of FS, the aesthetic outcome, economic results, and other complications were evaluated. Both acellular dermis and free fat grafts were effective in preventing FS with an equal rate of postoperative complications. Patients undergoing free fat grafting had a significantly higher aesthetic score and lower cost than those undergoing acellular dermis grafting. Free fat grafting has equal risks but more advantages compared with acellular dermis. Free fat grafting is an effective, convenient, and inexpensive option for parotidectomy defect reconstruction. 1b.


Brain norepinephrine and convulsions in the genetically epilepsy-prone rat: sex-dependent responses to Ro 4-1284 treatment.
Seizure predisposition in the Genetically Epilepsy-Prone Rat (GEPR) is at least partially dependent on central nervous system noradrenergic deficits. We have previously shown that moderate seizure GEPRs (GEPR-3) experience an increase in seizure severity after receiving Ro 4-1284, a monoamine vesicle inactivating drug. We are now reporting the effect of this drug on severe seizure GEPRs (GEPR-9). Motives for this study were: (a) to determine the effects of further depletion of innately deficient monoaminergic stores on seizure latencies and (b) to investigate whether a previously documented seizure severity difference between the sexes is related to the defective monoaminergic system in these subjects. GEPR-9s with known seizure history were tested for latency to onset of running phase and convulsion 45 minutes after Ro 4-1284 or saline administration. Brain norepinephrine levels were also determined. Ro 4-1284 caused severe depletion of monoamines in all brain areas assayed in both sexes of GEPR-9s and also caused a reduction in the latencies for onset of running and convulsion. The drug-induced norepinephrine depletion across the brain areas surveyed was significantly greater in females than in their male littermates. These observations prompt us to postulate that noradrenergic neurons in female GEPR-9s are functionally different from those in males and that this difference is detected in the differential effectiveness of Ro 4-1284 between the two sexes. Also, the influence of gonadal hormones on seizure predisposition and on the neurochemical actions of Ro 4-1284 may be different in GEPR-9 males and females.


Eating out of the hand, maggots--friend or foe?
The presence of maggots (fly larvae) in an open wound is a repelling sight to many and documented cases of myiasis in the literature are scant due to the rarity of such infestation in live patients. A unique case of such a presentation is elaborated in a patient who sustained a crush injury to the hand. This case serves to highlight the unique challenges faced in treating such injuries and to raise the profile of maggots and their untapped potential use in biodebridement and management of open wounds in modern day wound care practices.


Parental perspectives on promoting physical activity for their children surviving cancer: A qualitative study.
Physical activity is vital for the healthy development of pediatric cancer survivors. We aimed to explore parental perception on the importance, the barriers to and facilitators of participating in physical activity for their children surviving cancer. A qualitative study, using a descriptive phenomenological approach, was conducted. Purposive sample of parents of pediatric cancer survivors aged 9-16 years and had completed treatment at least six months previously were participated in one-to-one semi-structured interviews conducted by two trained research nurses. Data analysis followed Colaizzi's descriptive phenomenology method. Twenty-eight parents (64.3 % female) of pediatric cancer survivors were interviewed. Most parents lacked awareness and knowledge regarding the importance and benefits of physical activity in their child's survivorship. Major barriers identified were parental concern about their child performing physical activity, time constraints and lack of recreational facilities and activity provision. Parents reported that parental support, family involvement and child's interests and enjoyment appeared to be crucial facilitators of survivors' physical activity. This study identified the barriers to and facilitators of engaging in physical activity of pediatric cancer survivors from the parental perspectives. The findings of the study is important for the development of health education to promote regular physical activity among pediatric cancer survivors.


The influence of linoleic acid intake on the excretion of urinary prostaglandin metabolites.
The influence of linoleic acid intake on human prostaglandin formation was investigated by gas chromatographic determination of dimethyl tetranorprostanedioate, a derivative of the major urinary end products of prostaglandin metabolism. Six healthy female volunteers were put on liquid formula diets. Each person had a linoleic acid supply of 0, 10, and 50 g per day for periods of two weeks. At the end of these periods the corresponding average amounts of tetranorprostanedioic acid in urine were 92, 175, and 326 microgram per day.


The effect of McN-A-343 on muscarinic receptors in the cerebral cortex and heart.
McN-A-343 behaves as a competitive agonist in binding to muscarinic receptors in the cerebral cortex. In its interaction with myocardial muscarinic receptors it is not competitive but it retains features of agonist binding.


Underestimation of prevalence of raised blood sugar from history compared to biochemical estimation: support for the WHO rule of halves in a population based survey in Eritrea of 2009.
To ascertain the prevalence of diabetes mellitus from history and biochemical estimation so as to attest the WHO Rule of halves in a lean population. A population based national survey on diabetes mellitus was carried out in 2009. History and fingerpicks blood analysis were examined according to recommended procedures of the WHO STEPwise approach and the WHO recommended automated machine to compare the two modalities of estimating diabetes prevalence. Over 6000 people with a response rate of 95 % and a prevalence of raised blood glucose of 5.0 %. The prevalence from history of raised blood sugar was 2.2 %. Less than half (47 %) of the persons with high blood glucose were aware of their status with less than half on treatment. Of those on treatment less than half (30 %) were well controlled. Prevalence of raised fasting blood glucose was more than double that estimated from history, with less than half of the people aware of their status and of those on treatment nearly half are under good control. The underestimation of the disease through history supports the WHO rule of halves and calls for the use of biochemical tests when estimating prevalence of diabetes in the general population or at least doubling the rate from history alone.


Percutaneous removal of biliary stones.
Since 1983 we have performed percutaneous treatment of biliary lithiasis in 97 patients. Previous retrograde endoscopic procedures were incomplete or infeasible in all patients. Immediate results were excellent resulting in complete resolution of lithiasis in 89 of 97 patients (92%). In 4 patients (4%) partial success was obtained (symptoms subsided although there were nonobstructing residual stones). Percutaneous treatment failed in 1 patient (1%). Three patients died. Complications occurred in 14 of 97 patients (14%) and mortality at 30 days was 3%. Long-term results were evaluated in 71 patients who had a least a 6-month follow-up (mean 31 months and range 6-78 months). Eight of 71 patients (11%) had recurrence of stones and 7 of these were successfully retreated transhepatically. Percutaneous removal of biliary stones is efficacious because it has a high cure rate, a low complication rate, and a mortality rate that compares favorably to that of surgery even though the patients are usually older and in poorer general condition.


Transformation of psi- Saccharomyces cerevisiae to psi+ with DNA co-purified with 3 micron circles.
DNA enriched for supercoiled plasmids prepared from the 3 micron plasmid-enriched, [psi+], [2 micron degrees] strain 6-1G-P188 and from the [2 micron+] [psi+] strain LL20 can be used to transform a psi- recipient strain to psi+. Fractionation of the former preparation by electrophoresis showed that the 3 micron plasmid band contained the transforming activity.


(Z)-N-[(Z)-3-(2,4-Dimethyl-phenyl-imino)-butan-2-yl-idene]-2,4-dimethyl-aniline.
The asymmetric unit of the title compound, C(20)H(24)N(2), contains one half -mol-ecule which exhibits a crystallographically imposed center of symmetry. The benzene rings are inclined to the 1,4-diaza-butadiene mean plane by 78.3 (2)°.


Antibiotic treatment of diarrhoea is associated with decreased time to the next diarrhoea episode among young children in Vellore, India.
Antibiotics are commonly given for the treatment of childhood diarrhoea, but are not indicated in most cases. Antibiotics modify the gastrointestinal microbiota, which may have unanticipated effects on the risk of subsequent diarrhoea. In a prospective observational cohort study, we assessed the effect of caregiver-reported antibiotic treatment for diarrhoea on the timing of a child's next episode among 434 children followed from birth to 3 years of age in Vellore, India. We estimated median time differences and time ratios from inverse probability of exposure-weighted Kaplan-Meier curves for the time to next diarrhoea episode, comparing children who did and did not receive antibiotics for the previous episode. Study children had more than five diarrhoea episodes on average in the first 3 years of life, and more than a quarter of all episodes were treated with antibiotics. Children who received antibiotics for their first diarrhoea episode had their second episode on average 8 weeks earlier (median time difference: -8, 95% confidence interval: -10, -3) than children who did not receive antibiotics. The effects of antibiotics on subsequent diarrhoea were greatest at earlier episodes and younger ages, and cefixime had a slightly larger effect compared with cotrimoxazole. Antibiotic treatment of diarrhoea was associated with reduced time to a subsequent diarrhoea episode, especially among younger infants. Whereas rational use of antibiotics has been advocated to reduce antimicrobial resistance in populations, we show that overuse of antibiotics may also have a direct adverse effect on individual patients.


Effect of indomethacin on water intake of the rat.
Indomethacin stimulated water intake in intact rats. This effect could also be demonstrated in bilaterally ureteral ligated rats, but it was totally abolished after bilateral nephrectomy. It is suggested that the stimulatory effect of indomathacin on water consumption is mediated by a renal factor.


Recent improvements in the UNO BP monitor/conditioner.
A number of modifications and improvements have been made in the UNO system for monitoring and conditioning blood pressure, which have increased its accuracy and versatility. The purpose of this report, therefore, is to enumerate and describe the major changes in the present generation of the system.


Fabrication of a stable surgical template using staged tooth extraction for immediate implant placement.
When a patient with a nonrestorable dentition desires an immediate restoration, fabrication and use of a stable surgical template can be challenging. Conventionally made surgical templates may lack stability and may, therefore, be less predictable. This article describes the fabrication of a surgical template that permitted the use of staged tooth extraction to facilitate predictable immediate implant placement in a patient with a nonrestorable dentition.


Reduction in brain serotonin synthesis rate following chronic methamphetamine administration in rats.
Chronic administration of methamphetamine (20 mg/kg i.p., every 12 h for 6 days) produced significant decreased in brain 5-hydroxytryptophan accumulation following decarboxylase inhibition and 5-hydroxyindoleacetic acid accumulation following probenecid treatment in rats. Administration of fluoxetine prior to each methamphetamine injection prevented these neurochemical changes. Acute methamphetamine treatment produced no changes in these neurochemical measures. These data demonstrate that chronic, but not acute, methamphetamine treatment reduces brain serotonin synthesis rate.


Relationship between the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale in a sleep laboratory referral population.
Sleep health questionnaires are often employed as a first assessment step for sleep pathology. The Epworth Sleepiness Scale (ESS) and the Pittsburgh Sleep Quality Index (PSQI) are two commonly employed questionnaire instruments. Aspects of sleep health may be measured differently depending on choice of instrument. In a patient population at high risk for sleep disorders, referred for polysomnography (PSG), we evaluated the level of association between results from these two instruments. Questionnaire results were also compared with measured PSG parameters. Records of patients undergoing overnight PSG in the sleep laboratory between February-June 2011 were retrospectively reviewed for eligibility. Inclusion criteria were met by 236 patients. PSQI and ESS scores, demographic information, and PSG data were extracted from each record for analysis. Four subgroups based on normal/abnormal values for ESS and PSQI were evaluated for between-group differences. Of 236 adult participants, 72.5% were male, the mean age was 52.9 years (13.9), mean body mass index (BMI) 34.4 kg/m(2) (8.3), mean ESS 9.0 (4.8; range: 0-22), PSQI mean 8.6 (4.2; range: 2-19). The Pearson correlation coefficient was r = 0.13 (P = 0.05) for association between ESS and PSQI. Participants with an abnormal ESS were more likely to have an abnormal PSQI score (odds ratio 1.9 [1.1-3.6]; P = 0.03). Those with an abnormal ESS had higher BMI (P = 0.008) and higher apnea-hypopnea indexes (AHI) (P = 0.05). Differences between the four subgroups were observed for BMI and sex proportions, but not for AHI. We observed limited association between these two commonly used questionnaire instruments, the ESS and the PSQI. These two questionnaires appear to evaluate different aspects of sleep. In terms of clinical application, for global assessment of patients with sleep problems, care should be taken to include instruments measuring different facets of sleep health.


Centering Community Voices: Establishment of a Community Advisory Board at a Student-Run Free Clinic.
Student-run free clinics (SRFCs) are common throughout the U.S. and have potential to meet the needs of both health professions trainees and patients in underserved communities. Here, we describe our SRFC's initial process for recruiting, implementing, and evaluating a Community Advisory Board to better align clinic offerings with community needs.


Usefulness of automated image analysis for recognition of the fragile X syndrome gestalt in Congolese subjects.
Computer-aided software such as the facial image diagnostic aid (FIDA) and Face2Gene has been developed to perform pattern recognition of facial features with promising clinical results. The aim of this pilot study was to test Face2Gene's recognition performance on Bantu Congolese subjects with Fragile X syndrome (FXS) as compared to Congolese subjects with intellectual disability but without FXS (non-FXS). Frontal facial photograph from 156 participants (14 patients with FXS and 142 controls) predominantly young-adults to adults, median age 18.9 age range 4-39yo, were uploaded. Automated face analysis was conducted by using the technology used in proprietary software tools called Face2Gene CLINIC and Face2Gene RESEARCH (version 17.6.2). To estimate the statistical power of the Face2Gene technology in distinguishing affected individuals from controls, a cross validation scheme was used. The similarity seen in the upper facial region (of males and females) is greater than the similarity seen in other parts of the face. Binary comparison of subjects with FXS versus non-FXS and subjects with FXS versus subjects with Down syndrome reveal an area under the curve values of 0.955 (p = 0.002) and 0.986 (p = 0.003). The Face2Gene algorithm is separating well between FXS and Non-FXS subjects.


The orthodontic management of patients with cleft lip and palate: from the permanent dentition and the adult returning to the service.
This is the second of two papers outlining the orthodontic management of patients with cleft lip and palate. The first paper reviewed orthodontic input into children with cleft lip and palate from birth to the late mixed dentition before definitive orthodontics. In this second paper, I will discuss tooth management across the grafted cleft site and its impact on the bone graft itself. I will also discuss the some of the challenges of the adult patient returning to the service.


Direct Labeling of Protein Nanoparticles with Fluorescent Compounds for Immunoassay Applications.
A fusion protein, designated ELP-D-C, comprised of a hydrophobic elastin-like polypeptide unit, a hydrophilic aspartic acid-rich peptide unit, and an antibody-binding domain as a functional unit, was constructed. Upon heat induction, ELP-D-C forms micellar nanoparticles displaying antibody-binding domains on their surfaces. The protein nanoparticles were able to incorporate hydrophobic fluorescent compounds and subsequently detect target molecules via antibody binding by the resulting fluorescence intensity, which was proportional to the log of the concentration of the target molecule.


Development of 3D printed mini-waffle shapes containing hydrocortisone for children's personalized medicine.
Hydrocortisone is mainly used in the substitution treatment of adrenal insufficiency which results in a dysregulation of cortisol. Compounding of hydrocortisone capsules remains the only low-dose oral treatment suitable for the pediatric population. However, capsules often show non-compliance in mass and content uniformity. Three-dimensional printing offers the prospect of practising personalized medicine for vulnerable patients like children. The goal of this work is to develop low-dose solid oral forms containing hydrocortisone by hot-melt extrusion coupled with fused deposition modeling for the pediatric population. Formulation, design and processes temperatures were optimized to produce printed forms with the desired characteristics. Red mini-waffle shapes containing drug loads of 2, 5 and 8 mg were successfully printed. This new 3D design allow to release more than 80 % of the drug in 45 min indicating a conventional release like the one obtained with capsules. Mass and content uniformity, hardness and friability tests complied with European Pharmacopeia specifications, despite the considerable challenge of the small dimensions of the forms. This study demonstrates that FDM can be used to produce innovative pediatric-friendly printed shapes of an advanced pharmaceutical quality to practice personalize medicine.


New way of purification of pathogenic rickettsiae reducing health risks.
In general, cultivation and purification of intracellular pathogenic rickettsiae represents a risk for laboratory personnel due to exposure to highly infectious aerosol or accidental inoculation during these procedures. In this study, we describe an alternative, effective and time saving technique for rickettsial purification using digitonin to release intracellular bacteria from host cell without physical disruption. No significant differences were noted in yield and infectivity between digitonin treated rickettsiae and rickettsiae purified by sonication. This is the first report of using digitonin in purification of pathogenic rickettsiae and this approach might be effective for other intracellular pathogenic bacteria.


Analytical procedure for the determination of the new antitumour drug N-benzoylstaurosporine and three potential metabolites in human plasma by reversed-phase high-performance liquid chromatography.
The staurosporine derivative, N-benzoylstaurosporine (CGP 41 251; I), is a protein kinase C inhibitor that has been selected for phase I clinical evaluation in cancer patients. We have developed a selective and sensitive assay of the drug and three potential metabolites in human plasma. The method is based on reversed-phase high-performance liquid chromatography with fluorescence detection. The sample pretreatment involves liquid-liquid extraction with diisopropyl ether with recoveries over 88%. The limit of detection and limit of quantitation of the parent compound and two metabolites were 0.5 and 1.0 ng/ml, respectively. For the third metabolite the limit of detection and limit of quantitation were 1.0 and 2.0 ng/ml, respectively. Linear calibration lines were obtained over the range of 1-1000 ng/ml. The between-day and within-day precisions were < 7.1% for all the analytes. In plasma the compounds were stable for at least one month if stored at -30 degrees C or below. The applicability of the method for in vivo studies has been demonstrated in a pharmacokinetic study in rat receiving 0.5 mg/kg of the drug as an intravenous bolus injection. Compound I and two metabolites were detected.


Chemical Synthesis of Proteins with Base-Labile Posttranslational Modifications Enabled by a Boc-SPPS Based General Strategy Towards Peptide C-Terminal Salicylaldehyde Esters.
Chemical synthesis of proteins bearing base-labile post-translational modifications (PTMs) is a challenging task. For instance, O-acetylation and S-palmitoylation PTMs cannot survive Fmoc removal conditions during Fmoc-solid phase peptide synthesis (SPPS). In this work, we developed a new Boc-SPPS-based strategy for the synthesis of peptide C-terminal salicylaldehyde (SAL) esters, which are the key reaction partner in Ser/Thr ligation and Cys/Pen ligation. The strategy utilized the semicarbazone-modified aminomethyl (AM) resin, which could support the Boc-SPPS and release the peptide SAL ester upon treatment with TFA/H2 O and pyruvic acid. The non-oxidative aldehyde regeneration was fully compatible with all the canonical amino acids. Armed with this strategy, we finished the syntheses of the O-acetylated protein histone H3(S10ac, T22ac) and the hydrophobic S-palmitoylated peptide derived from caveolin-1.


Decreased expression of Sushi Domain Containing 2 correlates to progressive features in patients with hepatocellular carcinoma.
Sushi Domain Containing 2 (SUSD2) has been identified as a regulator of colon and breast cancer. Increasing evidence suggests that SUSD2 plays a key role in tumorigenesis. However, the SUSD2 expression status and its functions in hepatocellular carcinoma (HCC) are still unrevealed. In the present study, we intended to investigate SUSD2 expression status and its correlation with the clinicopathological features in HCC patients. Furthermore,we examined the influence of SUSD2 on the proliferation, apoptosis, invasion and migration of the HCC cell lines HepG2 and SMMC7721. We evaluated the SUSD2 expression in HCC tissues and paired normal liver tissues by quantitative real-time PCR and western blotting analysis. The clinicopathological significance of SUSD2 was investigated by immunohistochemistry (IHC) on a HCC tissue microarray. Receiver operating characteristic (ROC) analysis was applied to determine the optimal cut-off score for positive expression of SUSD2. The correlation between SUSD2 protein expression and clinicopathological features of HCC was analyzed by Chi square test. The cell proliferation, apoptosis, invasion and migration potential were observed to detect the functions of SUSD2 in HCC cells. Decreased expression of SUSD2 mRNA and protein were observed in the majority of HCC tissues, compared with paired normal liver tissues. When SUSD2 high expression percentage was determined to be above 52.5 % (area under ROC curve = 0.769, P = 0.000), low expression of SUSD2 was observed in 62.2 % (112/180) of HCC tissues and high expression of SUSD2 was observed in all normal liver tissues (16/16) by IHC. Decreased expression of SUSD2 in patients was correlated with high histological grade (χ(2) = 5.198, P = 0.023), advanced clinical stage (χ(2) = 30.244, P = 0.000), pT status (χ(2) = 33.175, P = 0.000), pN status (χ(2) = 4.785, P = 0.029), pM status (χ(2) = 4.620, P = 0.032). Down-regulation of SUSD2 promoted cell proliferation,invasion and migration,reduced the cell apoptosis. Our findings suggest that SUSD2 may play as a tumor suppressor in HCC cells and could be served as an additional potential marker for diagnosis.


Pineal and ocular influences on male and female turkeys: plasma luteinizing hormone and prolactin levels during gonadal development.
Plasma levels of prolactin (PRL) and luteinizing hormone (LH) were determined in pinealectomized (PX) and/or bilateral ocular enucleated (EX) turkey hens and toms during gonadal development. Measurements were obtained weekly for 6 weeks following photo-induced ovarian recrudescence in adult hens and biweekly from 12 to 34 weeks of age in sexually developing toms. Both hens and toms were maintained on a photoperiod of 16L:8D. Plasma PRL levels were significantly correlated with time (P less than 0.01) and were linear with significant slopes (P less than 0.01) in all treatment groups of hens and toms. However, the regression coefficients were positive for the hens and negative for the toms. Both PX and EX reduced PRL levels in the hens. PX did not significantly affect PRL levels of toms but EX depressed PRL levels. In hens LH was not correlated with weeks of photostimulation but in toms LH was positively correlated to age and linear with significant slopes in all treatment groups. There were no significant treatment effects on plasma LH levels of hens or toms. It was concluded that neither the pineal gland nor the eyes affect plasma LH levels of male turkeys during testicular development or female turkeys during photostimulated ovarian recrudescence. Although the eyes affected plasma PRL of both males and females during gonadal development, the pineal only influenced female PRL levels.


Expression of porcine pseudorabies virus genes by a bovine herpesvirus-1 (infectious bovine rhinotracheitis virus) vector.
Recombinant DNA techniques were used to insert foreign genes into bovine herpesvirus-1 [infectious bovine rhinotracheitis virus (IBRV)] vectors which were attenuated by deletion and/or insertion mutations in the IBRV thymidine kinase (tk) gene. In one recombinant, the regulatory and coding sequences of the late pseudorabies virus (PRV) glycoprotein gIII gene, were inserted into the early IBRV tk gene. This recombinant efficiently expressed the PRV gIII gene indicating that immediate early IBRV proteins were competent to transactivate the late PRV gIII gene. IBRV vector viruses were also prepared in which the coding sequences of the early PRV tk gene, the late PRV gIII gene, and the E. coli beta-galactosidase gene were ligated to the late IBRV gIII promoter. Genotypes and phenotypes of the recombinant viruses were verified by restriction endonuclease and molecular hybridization experiments, thymidine plaque autoradiography, beta-gal plaque assays, and by immunoprecipitation experiments on extracts from 3H-mannose-labelled cells. The recombinant IBRV expressing beta-gal from the IBRV gIII promoter has been useful as an intermediate in the construction of IBRV vectors harboring foreign DNA sequences. The infectivity of the IBRV recombinant that expressed PRV gIII from the IBRV gIII promoter, was neutralized by polyclonal PRV antisera and by monoclonal antibodies to PRV gIII. The PRV gIII glycoprotein synthesized by the preceding recombinant has been used to coat microtiter test plate wells in a PRV gIII differential diagnostic test kit.


Historical records of mercury in southern latitudes over 1600 years: Lake Futalaufquen, Northern Patagonia.
Mercury is released to the environment from natural and anthropogenic sources, and through atmospheric transport is distributed globally. Lake Futalaufquen (42.8°S) is an oligotrophic lake located in Los Alerces National Park (Northern Patagonia), providing a remote and unpolluted study system. A lacustrine sedimentary sequence revealed 1600 years of Hg deposition, identifying natural baselines and marked peaks not correlated with long-range atmospheric transport. Organic matter and catchment erosion were discarded as Hg drivers. Natural background, pre-1300 CE Hg concentrations, ranged between 27 and 47 ng g(-1) (accumulation rates from 8 to 15μg m(-2) y(-1)). From 1300 CE on, the Hg background profile did not follow the generally increasing Hg pattern observed in both Southern and Northern Hemisphere since pre-industrial times. It was not until the last century that a 1.6-fold increase is observed in the Hg accumulation rate, considered among the lowest increments in southern South America. Noteworthy local/regional sources of Hg for this area, along with global transport, are forest fires and volcanic activity. Between approx. 1340 and 1510 CE, sharp increase in Hg concentration and accumulation rate (up to 204 ng g(-1) and 51 μg m(-2) y(-1), respectively) were clearly associated with extended fire episodes. Furthermore, high Hg peaks during the last 300 years were associated with volcanic eruptions in northernmost Patagonia together with fairly irregular fire episodes, caused by anthropogenic burning by settling population in the Andes.


Effects of contralateral denervation on quantal output and gross nerve terminal morphology in mouse muscles.
We have studied the effect of unilateral denervation on the quantal output and gross nerve terminal morphology of the contralateral tensor fascia latae (TEL) muscle in mice. Unilateral TFL denervation was achieved by resecting spinal nerves L4 and L5. We found no significant difference, in quantal output or in the percentage of nerve terminals with sprouts, between the contralateral muscles and muscles in unoperated, age-matched control mice, at 4 days, 11-12 days or 6.5 months after denervation. This finding is in contrast to marked differences between similar experimental and control muscles after unilateral denervation reported in frogs by others.


The Protective Effect of Vitamin D on Dementia Risk in Hemodialysis Patients.
Patients with end-stage renal disease (ESRD) undergoing hemodialysis are at an elevated risk of developing dementia, potentially linked to the high prevalence of vitamin D deficiency in this population, which may contribute to cognitive impairment. Nevertheless, the impact of vitamin D supplementation on the risk of dementia in hemodialysis patients remains uncertain, necessitating further investigation to elucidate the potential benefits of vitamin D intervention in this vulnerable group. In this propensity-score-matched comparative cohort study, we sought to assess the impact of vitamin D supplementation on the occurrence of dementia in patients with end-stage renal disease (ESRD) undergoing hemodialysis. A total of 1424 patients were included and matched 1:1 using propensity scores. The study population was divided into two groups: those receiving vitamin D supplementation at a dose of ≥70 μg/week and those without any supplementation. The primary outcome of interest was the incidence of dementia. We calculated adjusted hazard ratios (aHRs) to examine the association between vitamin D supplementation and the risk of dementia while controlling for relevant covariates. The adjusted hazard ratio (aHR) comparing vitamin D supplementation to no supplementation was 0.44 (95% CI 0.29-0.69; p < 0.0001), demonstrating a significant decrease in the risk of dementia associated with vitamin D supplementation. The aHRs for vitamin D supplementation at different dose ranges (70-105, 106-350, 351-1000, and >1000 μg/week) were 0.51, 0.49, 0.43, and 0.41, respectively (p for trend < 0.0001). These findings suggest a potential dose-dependent relationship between vitamin D supplementation and the reduction of dementia risk. In our study, we found that vitamin D supplementation at doses of ≥70 μg/week significantly reduced the risk of dementia in patients with end-stage renal disease (ESRD) undergoing hemodialysis. Furthermore, our results indicated a dose-dependent effect, with higher doses of supplementation correlating with a greater reduction in dementia risk. These findings underscore the potential of vitamin D supplementation as a preventive approach for cognitive impairment in this high-risk population.


Preoperative imaging evaluation of potential living liver donors: reasons for exclusion from donation in adult living donor liver transplantation.
Accurate pretransplant evaluation of a potential donor in living donor liver transplantation (LDLT) is essential in preventing postoperative liver failure and optimizing safety. The aim of this study was to investigate the reasons for exclusion from donation of potential donors in adult LDLT. From September 2003 to June 2006, 266 potential donors were evaluated for 215 recipients: 220 potential donors for 176 adult recipients; 46 for 39 pediatric recipients. Imaging modalities including Doppler ultrasound, computerized tomography (CT), and magnetic resonance (MR) angiography provided vascular evaluation and MR cholangiopancreatography to evaluate biliary anatomy. Calculation of liver volume and assessment of steatosis were performed by enhanced and nonenhanced CT, respectively. In the adult group, only 83 (37.7%) potential donors were considered suitable for LDLT. Of the 137 unsuitable potential donors, 36 (26.2%) candidates were canceled because of recipient issues that included death of 15 recipients (10.9%), main portal vein thrombosis (8%), recipient condition beyond surgery (5%), and no indication for liver transplantation due to disease improvement (2%). The remaining 101 (73.8%) candidates who were excluded included steatosis (27.7%), an inadequate remnant volume (57.4%), small-for-size graft (8.9%), HLA-homozygous donor leading to one-way donor-recipient HLA match (3%), psychosocial problems (4%), as well as variations of hepatic artery (4%), portal vein (1%), and biliary system anatomy (5%). Anatomic considerations were not the main reason for exclusion of potential donors. An inadequate remnant liver volume (< 30%) is the crucial point for the adult LDLT decision.


Multichannel intracranial recording device using a color imaging brain mapping system.
A procedure is described for the manufacture and use of a multichannel (up to 20) intracranial recording device. Electrodes are arranged in a horizontal plane, and can be controlled by a conventional microdrive. Data from multiple channels are visualized and analyzed utilizing a commercially available color imaging brain mapping system. Potential research applications include studies of neural generators of evoked responses through the simultaneous recording of intracranial and scalp potentials.


Moment-based texture segmentation of luminal contour in intravascular ultrasound images.
A system for luminal contour segmentation in intravascular ultrasound images is proposed. Moment-based texture features are used for clustering of the pixels in the input image. After the clustering, morphological smoothing and a boundary detection process are applied and the final image is obtained. The proposed method was applied to 15 images from different patients, and a correlation coefficient of 0.86 was obtained between the areas of lumen automatically and manually defined. Moment-based texture features together with the radial feature are powerful tools for identification of the lumen region in intravascular ultrasound images. Morphological filtering was useful for improving the segmentation results.


Drug Insight: biological effects of botulinum toxin A in the lower urinary tract.
Botulinum toxins can effectively and selectively disrupt and modulate neurotransmission in striated muscle. Recently, urologists have become interested in the use of these toxins in patients with detrusor overactivity and other urological disorders. In both striated and smooth muscle, botulinum toxin A (BTX-A) is internalized by presynaptic neurons after binding to an extracellular receptor (ganglioside and presumably synaptic vesicle protein 2C). In the neuronal cytosol, BTX-A disrupts fusion of the acetylcholine-containing vesicle with the neuronal wall by cleaving the SNAP-25 protein in the synaptic fusion complex. The net effect is selective paralysis of the low-grade contractions of the unstable detrusor, while still allowing high-grade contraction that initiates micturition. Additionally, BTX-A seems to have effects on afferent nerve activity by modulating the release of ATP in the urothelium, blocking the release of substance P, calcitonin gene-related peptide and glutamate from afferent nerves, and reducing levels of nerve growth factor. These effects on sensory feedback loops might not only help to explain the mechanism of BTX-A in relieving symptoms of overactive bladder, but also suggest a potential role for BTX-A in the relief of hyperalgesia associated with lower urinary tract disorders.


Loss of odor-induced c-Fos expression of juxtaglomerular activity following maintenance of mice on fatty diets.
Diet-induced obesity (DIO) decreases the number of OMP+ olfactory sensory neurons (OSN) in the olfactory epithelium by 25% and reduces correlate axonal projections to the olfactory bulb (OB). Whether surviving OSNs have equivalent odor responsivity is largely unknown. Herein, we utilized c-fos immediate-early gene expression to map neuronal activity and determine whether mice weaned to control (CF), moderately-high fat (MHF), or high-fat (HF) diet for a period of 6 months had changes in odor activation. Diet-challenged M72-IRES-tau-GFP mice were exposed to either a preferred M72 (Olfr160) ligand, isopropyl tiglate, or clean air in a custom-made Bell-jar infusion chamber using an alternating odor exposure pattern generated by a picosprizer™. Mice maintained on fatty diets weighed significantly more and cleared glucose less efficiently as determined by an intraperitoneal glucose tolerance test (IPGTT). The number of juxtaglomerular cells (JGs) decreased following maintenance of the mice on the MHF diet for cells surrounding the medial but not lateral M72 glomerulus within a 4 cell-column distance. The percentage of c-fos + JGs surrounding the lateral M72 glomerulus decreased in fat-challenged mice whereas those surrounding the medial glomerulus were not affected by diet. Altogether, these results show an asymmetry in the responsiveness of the 'mirror image' glomerular map for the M72 receptor that shows greater sensitivity of the lateral vs. medial glomerulus upon exposure to fatty diet.


A taxonomic study of the beetle cockroaches (Diploptera Saussure) from China, with notes on the genus and species worldwide (Blattodea: Blaberidae: Diplopterinae).
Four taxa of beetle cockroaches (Diploptera Saussure, 1864) from South China are described and illustrated, viz., two new species D. elliptica sp. n. and D. naevus sp. n., one new subspecies D. nigrescens guani subsp. n. and one widespread known species D. punctata (Eschscholtz, 1822). The genus and known species from around the world are discussed based on types and other specimens. D. pulchra Anisyutkin, 2007 is now regarded as a junior synonym of D. bicolor Hanitsch, 1925. Whether the populations of D. punctata represent or not different species needs to be studied in the future. A key, a distribution map, and photos of species are provided.


Nitric oxide exacerbates Al-induced inhibition of root elongation in rice bean by affecting cell wall and plasma membrane properties.
Aluminum (Al) toxicity is one of the most widespread problems for crop production on acid soils, and nitric oxide (NO) is a key signaling molecule involved in the mediation of various biotic and abiotic stresses in plants. Here we found that exogenous application of the NO donor sodium nitroprusside (SNP) exacerbated the inhibition of Al-induced root growth in rice bean [Vigna umbellata (Thunb.) Ohwi & Ohashi 'Jiangnan', Fabaceae]. This was accompanied by an increased accumulation of Al in the root apex. However, Al treatments had no effect on endogenous NO concentrations in root apices. These results indicate that a change in NO concentration is not the cause of Al-induced root growth inhibition and the adverse effect of SNP on Al-induced root growth inhibition should result from increased Al accumulation. Al could significantly induce citrate efflux but SNP had no effects on citrate efflux either in the absence or presence of Al. On the other hand, SNP pretreatment significantly increased Al-induced malondialdehyde accumulation and Evans Blue staining, indicating an intensification of the disruption of plasma membrane integrity. Furthermore, SNP pretreatment also caused greater induction of pectin methylesterase activity by Al, which could be the cause of the increased Al accumulation. Taken together, it is concluded that NO exacerbates Al-induced root growth inhibition by affecting cell wall and plasma membrane properties.


The ApoB/A-I ratio and metabolic syndrome in prepubertal children.
Studies about the relationship of apolipoproteins (apo) and metabolic syndrome in children are scarce. In this study, we analyze apo levels and determine the best cutoff point of the apoB/A-I ratio to diagnose dyslipidemia in prepubertal children with metabolic syndrome. A community-based, cross-sectional study that enrolled 337 children with Tanner stage 1 and average age and body mass index of 9.7±1.6 years and 19.2±3.8 kg/m(2) was carried out. Diagnosis of acute or chronic illnesses constituted the exclusion criteria; in addition, children undergoing medical treatment or receiving vitamins and/or oral supplements were not included. Metabolic syndrome was identified in 42 (12.5%) children (19 girls and 23 boys). The mean apoB/A-I ratio in the children with metabolic syndrome was 0.67±0.18. The best cutoff point of the apoB/A-I ratio for recognizing dyslipidemia was 0.60 (area under the receiver operating characteristic curve, 0.778; sensitivity 80%, specificity 55%). A total of 102 children exhibited apoB/A-I ratio ≥0.60. Diagnosis of metabolic syndrome was performed in 42 (41.2%) children. Among children with metabolic syndrome, 38 (90.5%) had hypertriglyceridemia, 34 (81.0%) low high-density lipoprotein cholesterol (HDL-C), 32 (76.2%) hypertriglyceridemia+low HDL-C, and 40 (95.2%) an apoB/A-I ratio ≥0.60. Our results show that the best cutoff point of the apoB/A-I ratio for recognizing dyslipidemia in prepubertal children is 0.60 and that among children with metabolic syndrome, an apoB/A-I ratio ≥0.60 is the marker of dyslipidemia with the highest frequency.


The synaptic ribbons of the guinea pig pineal gland in sterile, pregnant and fertile but non-pregnant females and in reproductively active males.
Pinealocyte ultrastructure has been studied in four sterile, four pregnant and three fertile but non-pregnant females, and also in three reproductively active male pigmented Duncan Hartley guinea pigs. Synaptic ribbons are dense, rod-like structures with a linear arrangement of clear vesicles periodically spaced on both sides of the rodlet. Although these structures were observed in the pinealocytes of all of the animals studied, they were scarce and difficult to locate in tissue from the fertile, non-pregnant females and from the reproductively active males. They were numerous in the pineal glands of the pregnant and sterile females. Typically they lie perpendicular to the cell membrane of the pinealocyte polar process and in close proximity to a polar process of a neighboring cell. The increased incidence of synaptic ribbons in pinealocytes which appear to be in a heightened state of activity strongly suggests a function for this structure. Synaptic ribbons are also present in sensory systems such as rods and cones of the retina, hair cells of the organ of Corti and hair cells of the vestibular apparatus. This fact, plus the photoreceptor function of pinealocytes in lower vertebrates, lends credence to the possibility that this structure may serve a sensory or receptor function in the guinea pig gland.


Development and evaluation of an eHealth self-management intervention for patients with chronic kidney disease in China: protocol for a mixed-method hybrid type 2 trial.
Chronic kidney disease (CKD) is a significant public health concern. In patients with CKD, interventions that support disease self-management have shown to improve health status and quality of life. At the moment, the use of electronic health (eHealth) technology in self-management interventions is becoming more and more popular. Evidence suggests that eHealth-based self-management interventions can improve health-related outcomes of patients with CKD. However, knowledge of the implementation and effectiveness of such interventions in general, and in China in specific, is still limited. This study protocol aims to develop and tailor the evidence-based Dutch 'Medical Dashboard' eHealth self-management intervention for patients suffering from CKD in China and evaluate its implementation process and effectiveness. To develop and tailor a Medical Dashboard intervention for the Chinese context, we will use an Intervention Mapping (IM) approach. A literature review and mixed-method study will first be conducted to examine the needs, beliefs, perceptions of patients with CKD and care providers towards disease (self-management) and eHealth (self-management) interventions (IM step 1). Based on the results of step 1, we will specify outcomes, performance objectives, and determinants, select theory-based methods and practical strategies. Knowledge obtained from prior results and insights from stakeholders will be combined to tailor the core interventions components of the 'Medical Dashboard' self-management intervention to the Chinese context (IM step 2-5). Then, an intervention and implementation plan will be developed. Finally, a 9-month hybrid type 2 trial design will be employed to investigate the effectiveness of the intervention using a cluster randomized controlled trial with two parallel arms, and the implementation integrity (fidelity) and determinants of implementation (IM step 6). Our study will result in the delivery of a culturally tailored, standardized eHealth self-management intervention for patients with CKD in China, which has the potential to optimize patients' self-management skills and improve health status and quality of life. Moreover, it will inform future research on the tailoring and translation of evidence-based eHealth self-management interventions in various contexts. Clinicaltrials.gov NCT04212923 ; Registered December 30, 2019.


Klebsiella pneumoniae meningitis in a 38-year-old Chinese traveller with impaired glucose tolerance: a new emerging syndrome?
Early diagnosis and appropriate empirical treatment of bacterial meningitis reduce morbidity and mortality. Prevalence rates of different causative pathogens associated with bacterial meningitis can depend on age, the underlying medical condition, way of infection and geographical distribution. Klebsiella pneumoniae represents an infrequent cause of community-acquired meningitis in South-East Asia and North-East Asia, where it accounts for 20% of all bacterial meningitis, frequently associated with septic metastatic complications. We describe a case of K. pneumoniae meningitis, diplopia and chemosis in a recently immigrated patient with impaired glucose tolerance. The reason for the high prevalence of metastatic septic infections caused by K. pneumoniae in Taiwan and South-East Asia remains unclear: high prevalence in this area of serotype K1 and K2 and the expression of a novel locus called magA conferring to bacterium an elevated phagocytosis resistance and an active proliferation ability have been suggested. A high degree of suspicion for this etiology must be taken into account in immigrants from China and Taiwan. Due to a very high lethality, guidelines on empiric treatment should be considered in the management of bacterial meningitis, with the patients geographical origin and the clinical syndrome (meningitis and endophtalmitis) as potential risk factors for K. pneumoniae infection.


Constructing Causal Life-Course Models: Comparative Study of Data-Driven and Theory-Driven Approaches.
Life-course epidemiology relies on specifying complex (causal) models that describe how variables interplay over time. Traditionally, such models have been constructed by perusing existing theory and previous studies. By comparing data-driven and theory-driven models, we investigated whether data-driven causal discovery algorithms can help in this process. We focused on a longitudinal data set on a cohort of Danish men (the Metropolit Study, 1953-2017). The theory-driven models were constructed by 2 subject-field experts. The data-driven models were constructed by use of the temporal Peter-Clark (TPC) algorithm. The TPC algorithm utilizes the temporal information embedded in life-course data. We found that the data-driven models recovered some, but not all, causal relationships included in the theory-driven expert models. The data-driven method was especially good at identifying direct causal relationships that the experts had high confidence in. Moreover, in a post hoc assessment, we found that most of the direct causal relationships proposed by the data-driven model but not included in the theory-driven model were plausible. Thus, the data-driven model may propose additional meaningful causal hypotheses that are new or have been overlooked by the experts. In conclusion, data-driven methods can aid causal model construction in life-course epidemiology, and combining both data-driven and theory-driven methods can lead to even stronger models.


Activation of TIMP-2/progelatinase A complex by stromelysin.
Progelatinase A was purified as a complex with TIMP-2 from the conditioned medium of a human glioblastoma cell line. The TIMP-2/progelatinase complex was resistant to the activation by p-aminophenylmercuric acetic acid (APMA), and showed less than 10% of the activity of the TIMP-2-free active enzyme. When the complex was incubated with stromelysin in the presence of APMA, the 64-kDa progelatinase was effectively converted to the 57-kDa mature enzyme, increasing its gelatinolytic activity about 8-fold. These results suggest that stromelysin is a natural activator of TIMP-2-bound progelatinase A.


Conflict Minerals in Electronic Systems: An Overview and Critique of Legal Initiatives.
The Democratic Republic of Congo has vast natural resources, many of which are regularly exploited by the electronics industry. Unfortunately, in addition to these resources, there are widespread human rights abuses committed by armed groups entrenched in the eastern part of the Democratic Republic of Congo. These armed groups are using profits from these minerals as a source of funding. Their human rights abuses have led to a growing humanitarian interest in the region and prompted the international community to action. This paper explores the conflicts in the Democratic Republic of Congo, provides an understanding of the link between human rights abuses and conflict minerals, and interprets and critiques the legal actions of the international community.


Long-term pattern of pleural effusion from chronic myeloid leukemia patients in second-line dasatinib therapy.
Dasatinib is a potent second-generation tyrosine kinase inhibitor approved for the treatment of chronic myeloid leukemia after imatinib failure. However, some patients treated with dasatinib experience pleural effusions (PEs). The determinants of pleural effusion in long-term dasatinib treatment (median 35 months, range 1-55) were investigated in single-center data of 65 patients enrolled in global phase 2 and phase 3 trials. Of the 65 patients, 35 (54%) developed dasatinib-induced pleural effusion (a median onset time, 20 months; range 0.2-54). The first pleural effusion developed in 15 (43%) patients within 12 months of dasatinib therapy. Disease phase (P = 0.02), dose schedule (P = 0.002) and actual daily mean dose (P = 0.0002) were significantly associated with an increased risk of pleural effusion. Twice-daily administration of dasatinib resulted in significantly more patients developing pleural effusions compared with the once-daily dosing schedule, particularly in advanced disease. In addition, a strong correlation was found between actual daily mean dose and time to onset of pleural effusions in patients treated with a daily mean dose >100 mg/day of dasatinib (P = 0.01). These data emphasize the need for dasatinib dose and schedule optimization and long-term monitoring of dasatinib-treated patients to prevent the negative clinical implications of pleural effusion.


FBXO31 modulates activation of hepatic stellate cells and liver fibrogenesis by promoting ubiquitination of Smad7.
Liver fibrosis is a critical pathological process in the early stage of many liver diseases, including hepatic cirrhosis and liver cancer. However, the molecular mechanism is not fully revealed. In this study, we investigated the role of F-box protein 31 (FBXO31) in liver fibrosis. We found FBXO31 upregulated in carbon tetrachloride (CCl4 ) induced liver fibrosis and in activated hepatic stellate cells, induced by transforming growth factor-β (TGF-β). The enforced expression of FBXO31 caused enhanced proliferation and increased expression of α-smooth muscle actin (α-SMA) and Col-1 in HSC-T6 cells. Conversely, suppression of FBXO31 resulted in inhibition of proliferation and decreased accumulation of α-SMA and Col-1 in HSC-T6 cells. In addition, upregulation of FBXO31 in HSC-T6 cells decreased accumulation of Smad7, the negative regulator of the TGF-β/smad signaling pathway, and suppression of the FBXO31 increased accumulation of Smad7. Immunofluorescence staining showed FBXO31 colocalized with Smad7 in HSC-T6 cells and in liver tissues of BALB/c mice treated with CCl4 . Immunoprecipitation demonstrated FBXO31 interacted with Smad7. Moreover, FBXO31 enhanced ubiquitination of Smad7. In conclusion, FBXO31 modulates activation of HSCs and liver fibrogenesis by promoting ubiquitination of Smad7.


Towards the development of a human in vitro model of the blood-brain barrier for virus-associated acute encephalopathy: assessment of the time- and concentration-dependent effects of TNF-α on paracellular tightness.
The pathogenesis of virus-associated acute encephalopathy (VAE) involves brain edema caused by disruption of the blood-brain barrier (BBB). We aimed to develop an in vitro VAE model using an in vitro BBB model, to evaluate the dynamics of vascular dysfunction caused by tumor necrosis factor (TNF)-α. A co-culture model, consisting of Transwell®-grown human brain microvascular endothelial cells and pericytes, was treated with serially diluted TNF-α. Transendothelial electrical resistance (TER) was measured using cellZscope®. A permeability assay, using fluorescein isothiocyanate-conjugated sodium or dextran, was performed. Changes in claudin-5 localization and expression after TNF-α treatment were observed using immunofluorescence staining and western blot analysis. The TER decreased and permeability increased after TNF-α treatment; recovery time was dependent on TNF-α concentration. Claudin-5 was delocalized after TNF-α treatment and recovered in a TNF-α concentration-dependent manner. The expression of claudin-5 decreased 24 h after the TNF-α treatment and completely recovered 48 h after TNF-α treatment. Claudin-5 delocalization was likely associated with vascular hyperpermeability. To conclude, we evaluated vascular endothelial cell permeability and injury in VAE using an in vitro BBB model treated with TNF-α. This system can be useful for developing novel therapeutic strategies for VAE and designing treatments that target vascular permeability.


SPOP-mutant prostate cancer: Translating fundamental biology into patient care.
Comprehensive cancer genome studies have revealed genetically-defined subtypes of prostate cancer with distinct truncal driver mutations. Because prostate cancer has been largely seen as a rather uniform disease, the clinical significance of this discovery remained largely obscure. However, recent findings imply distinct biological features and therapeutic vulnerabilities linked to specific truncal mutations. Here we review our current understanding of prostate cancers harboring recurrent point mutations in the ubiquitin ligase adaptor protein SPOP and discuss opportunities for future clinical translation. More specifically, activation of the androgen receptor (AR) signaling emerges as the key oncogenic pathway. SPOP-mutant prostate cancer patients respond to AR inhibition in various clinical settings. Molecular insights on how mutant SPOP promotes tumorigenesis may open more specific therapeutic avenues which, in combination with conventional AR-targeting agents, could improve the outcome of patients with SPOP-mutant prostate cancer.


A simple nomenclature for a complex proton pump: VHA genes encode the vacuolar H(+)-ATPase.
The vacuolar-type H(+)-ATPase acidifies intracellular compartments and is essential for many processes, including cotransport, guard cell movement, development, and tolerance to environmental stress. We have identified at least 26 genes encoding subunits of the vacuolar-type H(+)-ATPase in the Arabidopsis thaliana genome, although inconsistent nomenclature of these genes is confusing. The pump consists of subunits A through H of the peripheral V(1) complex, and subunits a, c, c" and d of the V(o) membrane sector. Most V(1) subunits are encoded by a single gene, whereas V(o) subunits are encoded by multiple genes found in duplicated segments of the genome. We propose to name these genes VHA-x, where x represents the letter code for each subunit. Applying a consistent nomenclature will help us to understand how the expression, assembly and activity of this pump are integrated with plant growth, signaling, development and adaptation.


Head and neck radiotherapy amid the COVID-19 pandemic: practice recommendations of the Italian Association of Radiotherapy and Clinical Oncology (AIRO).
Management of patients with head and neck cancers (HNCs) is challenging for the Radiation Oncologist, especially in the COVID-19 era. The Italian Society of Radiotherapy and Clinical Oncology (AIRO) identified the need of practice recommendations on logistic issues, treatment delivery and healthcare personnel's protection in a time of limited resources. A panel of 15 national experts on HNCs completed a modified Delphi process. A five-point Likert scale was used; the chosen cut-offs for strong agreement and agreement were 75% and 66%, respectively. Items were organized into two sections: (1) general recommendations (10 items) and (2) special recommendations (45 items), detailing a set of procedures to be applied to all specific phases of the Radiation Oncology workflow. The distribution of facilities across the country was as follows: 47% Northern, 33% Central and 20% Southern regions. There was agreement or strong agreement across the majority (93%) of proposed items including treatment strategies, use of personal protection devices, set-up modifications and follow-up re-scheduling. Guaranteeing treatment delivery for HNC patients is well-recognized in Radiation Oncology. Our recommendations provide a flexible tool for management both in the pandemic and post-pandemic phase of the COVID-19 outbreak.


Structured Rehabilitation for Patients with Atrial Fibrillation Based on an Integrated Care Approach: Protocol for a Prospective, Observational Cohort Study.
Guideline-recommended integrated care based on the ABC (Atrial fibrillation Better Care) pathway for "general" patients with atrial fibrillation (AF) improves clinical outcomes, as demonstrated in our prior mobile Atrial Fibrillation Application (mAFA)-II cluster randomized trial. The present study aims to investigate whether mAFA III-supported structured follow-up rehabilitation packages adapted to patient risk profiles and different treatment patterns (eg, for patients receiving drug treatment only, AF ablation, or left atrial appendage occlusion [LAAO]) will improve guideline adherence and reduce the risk of adverse cardiovascular events. In this prospective, observational mAFA III pilot cohort study, patients with AF aged ≥ 18 years will be enrolled using the mAFA III App for self-management. Assuming an annual rate of composite outcome of "ischaemic stroke or systemic embolism, all-cause death and cardiovascular hospitalization" of 29.3% for non-ABC pathway compliance compared with 20.8% for ABC pathway compliance, at least 1475 patients would be needed to detect the outcome of the A, B and C components of the ABC pathway, assuming a withdrawal rate of 20% in the first year. The primary endpoint is adherence to guidelines regarding the A, B and C components of the ABC pathway. Ancillary analyses will be performed to determine the impact of the ABC pathway using smart technologies on the outcomes among the "high-risk" population (eg, ≥75 years old, with multimorbidities, with polypharmacy) and the application of artificial intelligence machine-learning AF risk prediction management in assessing AF recurrence. The individualised anticoagulants with AF burden will be monitored by smart devices. ISRCTN13724416.


MiRNA-155 promotes proliferation by targeting caudal-type homeobox 1 (CDX1) in glioma cells.
MicroRNAs (miRNAs) play important roles in the tumorigenesis of glioma. Recent studies showed that miR-155 expression was increased in types of cancer, including glioma. However, the underlying mechanism of miR-155 on glioma is still unclear. In the present study, expression of miR-155 and caudal-type homeobox 1 (CDX1) was determined in glioma tissues by qRT-PCR, and the regulatory axis was further studied in glioma cells. We showed that miR-155 expression was significantly increased in glioma tissues while CDX1 expression was decreased. Correlation analysis revealed that miR-155 was negatively correlated with CDX1 expression in glioma tissues. Moreover, Kaplan-Meier analysis indicated that patients with high miR-155 expression had a poor overall survival. In addition, our results showed that the translation of CDX1 expression could be suppressed by miR-155 mimics. And miR-155 mimics promoted glioma cell proliferation could be reversed by CDX1 overexpression. In vivo assay, we showed that miR-155 overexpression promoted the progress of tumor formation. Therefore, we suggested that miR-155 might promote glioma cell growth partially by targeting CDX1, which provided a novel therapeutic strategy for glioma patients.


Carbofuran poisoning detected by mass spectrometry of butyrylcholinesterase adduct in human serum.
Carbofuran is a pesticide whose acute toxicity is due to inhibition of acetylcholinesterase. Butyrylcholinesterase (BChE) in plasma is inhibited by carbofuran and serves as a biomarker of poisoning by carbofuran. The goal was to develop a method to positively identify poisoning by carbofuran. Sera from an attempted murder and an attempted suicide were analyzed for the presence of carbofuran adducts on BChE. The BChE from 1 ml of serum was rapidly purified on a 0.2 ml procainamide-Sepharose column. Speed was essential because the carbofuran-BChE adduct decarbamylates with a half-life of about 2 h. The partially purified BChE was boiled to denature the protein, thus stopping decarbamylation and making the protein vulnerable to digestion with trypsin. The labeled peptide was partially purified by HPLC before analysis by LC/MS/MS in the multiple reaction monitoring mode on the QTRAP 2000 mass spectrometer. Carbofuran was found to be covalently bound to Ser 198 of human BChE in serum samples from two poisoning cases. Multiple reaction monitoring triggered MS/MS spectra positively identified the carbofuran-BChE adduct. In conclusion a mass spectrometry method to identify carbofuran poisoning in humans has been developed. The method uses 1 ml of serum and detects low-level exposure associated with as little as 20% inhibition of plasma butyrylcholinesterase.


Sex differences in cardiac rehabilitation enrollment: a meta-analysis.
The present systematic review and meta-analysis examines studies published in the past 10 years that described cardiac rehabilitation (CR) enrollment among women and men, to determine whether a significant sex difference persists despite the evidence supporting the benefits of CR to women as well as men. Scopus, MEDLINE, CINAHL, PsycINFO, PubMed, and The Cochrane Library databases were systematically searched for peer-reviewed articles published from July 2000 to July 2011. Titles and abstracts were screened, and the 623 selected full-text articles were independently screened based on predefined inclusion/exclusion criteria (guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses; PRISMA) and assessed for quality using the Strengthening the Reporting of Observational studies in Epidemiology (STROBE) statement form. The meta-analysis was undertaken using Review Manager software. Twenty-six eligible observational studies reporting data for 297,719 participants (128,499 [43.2%] women) were included. On average, 45.0% of men and 38.5% of women enrolled in CR. In the pooled analysis, men were more likely to be enrolled in CR compared with women (female enrollment vs male enrollment odds ratio, 0.64; 95% confidence interval, 0.57-0.72; P < 0.00001). Heterogeneity was considered high (I(2) = 78%). In the subgroup analyses, systematic CR referral during inpatient tertiary care resulted in significantly greater enrollment among women than nonsystematic referral. Overall, rates of CR enrollment among women are significantly lower compared with men, with women being 36% less likely to enroll in a rehabilitation program.


Utility of the CBCL DSM-Oriented Scales in Assessing Emotional Disorders in Youth with Autism.
Youth with autism spectrum disorder (ASD) are at risk for one or more emotional disorders (ED) including depressive and anxiety conditions. DSM-5 diagnostic guidelines indicate that co-occurring ED must be specified when present (APA, 2013). While ED may be evaluated for during initial diagnostic assessment, routine monitoring and screening is needed to identify emerging ED in later childhood and adolescence, a period of high risk. Confirmatory factor analysis, convergent and divergent validity analyses, criterion-related validity, and diagnostic accuracy analyses of the CBCL's Affective Problems and Anxiety Problems DSM Oriented Scales was completed on 93 well-characterized youth, ages 6 to 18 years with ASD (6:1 M:F), with and without intellectual impairment. These youth were from predominately white, middle-class backgrounds. Each scale measured a single construct reliably (depressive and anxiety disorders), neither scale measured symptoms of ASD, and youth with a depressive disorder had other ED co-morbidities. Findings demonstrate the DSM Oriented Affective and Anxiety Problem Scales can be used to screen for depression and anxiety in youth with ASD. Replication is needed with various subgroups representing gender, age, developmental level, autism, and mental health severity differences, and with groups across a broader set of demographics.


Culturally adapted psychosocial interventions (CaPSI) for early psychosis in a low-resource setting: study protocol for a large multi-center RCT.
Psychosis treatment guidelines recommend cognitive behaviour therapy (CBT) and family intervention (FI), for all patients with first episode psychosis (FEP), though guidance borrows heavily from literature in adults from high income countries. To our knowledge, there are few randomized controlled trials (RCTs) examining the comparative effect of these commonly endorsed psychosocial interventions in individuals with early psychosis from high-income countries and no such trials from low and middle-income countries (LMICs). The present study aims to confirm the clinical-efficacy and cost-effectiveness of delivering culturally adapted CBT (CaCBT) and culturally adapted FI (CulFI) to individuals with FEP in Pakistan. A multi-centre, three-arm RCT of CaCBT, CulFI, and treatment as usual (TAU) for individuals with FEP (n = 390), recruited from major centres across Pakistan. Reducing overall symptoms of FEP will be the primary outcome. Additional aims will include improving patient and carer outcomes and estimating the economic impact of delivering culturally appropriate psychosocial interventions in low-resource settings. This trial will assess the clinical-efficacy and cost-effectiveness of CaCBT and CulFI compared with TAU in improving patient (positive and negative symptoms of psychosis, general psychopathology, depressive symptoms, quality of life, cognition, general functioning, and insight) and carer related outcomes (carer experience, wellbeing, illness attitudes and symptoms of depression and anxiety). A successful trial may inform the rapid scale up of these interventions not only in Pakistan but other low-resource settings, to improve clinical outcomes, social and occupational functioning, and quality of life in South Asian and other minority groups with FEP. NCT05814913.


Brain Angiotensin II AT1 receptors are involved in the acute and long-term amphetamine-induced neurocognitive alterations.
Angiotensin II, by activation of its brain AT1-receptors, plays an active role as neuromodulator in dopaminergic transmission. These receptors participate in the development of amphetamine-induced behavioral and dopamine release sensitization. Dopamine is involved in cognitive processes and provides connectivity between brain areas related to these processes. Amphetamine by its mimetic activity over dopamine neurotransmission elicits differential responses after acute administration or after re-exposure following long-term withdrawal periods in different cognitive processes. The purpose of this study is to evaluate the AT1-receptor involvement in the acute and long-term amphetamine-induced alterations in long-term memory and in cellular-related events. Male Wistar rats (250-300 g) were used in this study. Acute effects: Amphetamine (0.5/2.5 mg/kg i.p.) was administered after post-training in the inhibitory avoidance (IA) response. The AT1-receptor blocker Losartan was administered i.c.v. before a single dose of amphetamine (0.5 mg/kg i.p.). Long-term effects: The AT1-receptors blocker Candesartan (3 mg/kg p.o.) was administered for 5 days followed by 5 consecutive days of amphetamine (2.5 mg/kg/day, i.p.). The neuroadaptive changes were evidenced after 1 week of withdrawal by an amphetamine challenge (0.5 mg/kg i.p.). The IA response, the neuronal activation pattern, and the hippocampal synaptic transmission were evaluated. The impairing effect in the IA response of post-training acute amphetamine was partially prevented by Losartan. The long-term changes induced by repeated amphetamine (resistance to acute amphetamine interference in the IA response, neurochemical altered response, and increased hippocampal synaptic transmission) were prevented by AT1-receptors blockade. AT1-receptors are involved in the acute alterations and in the neuroadaptations induced by repeated amphetamine associated with neurocognitive processes.


Valuing preferences for treating screen detected ductal carcinoma in situ.
Mammographic screening reduces breast cancer mortality but may lead to the overdiagnosis and overtreatment of low-risk breast cancers. Conservative management may reduce the potential harm of overtreatment, yet little is known about the impact upon quality of life. To quantify women's preferences for managing low-risk screen detected ductal carcinoma in situ (DCIS), including the acceptability of active monitoring as an alternative treatment. Utilities (cardinal measures of quality of life) were elicited from 172 women using visual analogue scales (VASs), standard gambles, and the Euro-Qol-5D-5L questionnaire for seven health states describing treatments for low-risk DCIS. Sociodemographics and breast cancer history were examined as predictors of utility. Both patients and non-patients valued active monitoring more favourably on average than conventional treatment. Utilities were lowest for DCIS treated with mastectomy (VAS: 0.454) or breast conserving surgery (BCS) with adjuvant radiotherapy (VAS: 0.575). The utility of active monitoring was comparable to BCS alone but was rated more favourably as progression risk was reduced from 40% to 10%. Disutility for active monitoring was likely driven by anxiety around progression, whereas conventional management impacted other dimensions of quality of life. The heterogeneity between individual preferences could not be explained by sociodemographic variables, suggesting that the factors influencing women's preferences are complex. Active monitoring of low-risk DCIS is likely to be an acceptable alternative for reducing the impact of overdiagnosis and overtreatment in terms of quality of life. Further research is required to determine subgroups more likely to opt for conservative management.


Pharmacological properties of motion vision in goldfish measured with the optomotor response.
In goldfish, the retinal pathways involved in motion coding have been demonstrated to have an L-cone dominated action spectrum (S. Schaerer, C. Neumeyer, Motion detection in goldfish investigated with the optomotor response is "color blind", Vision Res. 36 (1996) 4025-4034). The neurotransmitters involved in retinal motion coding mechanisms, and the relevance of these retinal motion coding mechanisms for motion perception, are little investigated in fish. In this study, the optomotor response was used to investigate the effect of antagonists on different receptor types for acetylcholine (ACh), GABA, for the dopamine D2-receptor (D2-R) - which is known to modulate the action spectrum in motion coding (C. Mora-Ferrer, K. Behrend, Dopaminergic modulation of photopic temporal transfer properties in goldfish retina investigated with the ERG, Vision Res. 44 (2004) 2067-2081) - and of an agonist for against the mGluR6-receptor (mGluR6) on goldfish motion vision in the photopic range. Blockade of nicotinic ACh-R, GABAa-R and both GABAa- and GABAc-R eliminated the optomotor response completely. Neither a muscarinic ACH-R antagonist, a D2-R antagonist or a mGluR6-agonist affected goldfish motion vision. The pharmacological profile of the goldfish optomotor response resembles the pharmacological profile of direction-selective ganglion cells (DS-GC) described for vertebrate retinas in electrophysiological experiments, e.g. (S. Weng, W. Sun, S. He, Identification of ON-OFF direction-selective ganglion cells in the mouse retina, J. Physiol. 562 (2005) 915-923). This indicates that cells with direction-selective receptive field properties exist in the goldfish retina. It is proposed that these cells provide the input for the full field motion perception in goldfish.


Metagenomic next-generation sequencing assists in the diagnosis of Cryptococcus pneumonia: Case series and literature review.
Pulmonary cryptococcosis (PC) was once thought to occur only in patients with immune deficiencies, such as tested positive for the Human Immunodeficiency Virus (HIV). However, in recent years, it has been discovered that more than half of the patients with PC in our nation are individuals with normal immune function. As more and more PC cases are recorded, our diagnosis and treatment approaches, as well as our understanding of PC, are gradually improving. In reality, most PC patients still have a high incidence of misdiagnosis on their initial visit. It is primarily linked to the diverse clinical manifestations, atypical imaging findings, and inaccurate diagnostic approaches. The research was conducted from 2019 to 2020. We performed traditional microbiological testing and mNGS on sample from patients with fever of Pulmonary nodules or lung infections. Furthermore, we collected patients' baseline information, clinical features, laboratory and imaging examination results, diagnosis, treatment and outcome. In the end, we confirmed three cases of PC using biopsy and mNGS. Our data demonstrates that mNGS can be utilized as an auxiliary method for PC diagnosis. Early mNGS aids in the identification of pathogens, enabling early diagnosis and treatment, as well as a reduction in the rate of misdiagnosis and illness progression.