Twenty-two-item Sino-Nasal Outcome Test in a control population: a cross-sectional study and systematic review.
The 22-item Sino-Nasal Outcome Test (SNOT-22) is a commonly utilized outcome measure for chronic rhinosinusitis (CRS). However, what constitutes a normal score remains poorly defined. The goal of this study was to evaluate SNOT-22 scores in a control population without CRS and perform a systematic review and meta-analysis of "normal" values. Ninety-nine subjects without CRS were enrolled, with 95 fully completing the SNOT-22 questionnaire. Multivariable linear regression was used to determine whether demographic factors or medical comorbidities influence SNOT-22 scores in a population without CRS. A systematic literature search was performed, identifying studies that evaluated the SNOT-22 in a non-CRS population and estimates for SNOT-22 values were pooled. Thirty-six males and 59 females were included in the primary analysis with a mean age of 53.4 ± 17.3 years (range, 18-88 years). The mean SNOT-22 score was 16.4 ± 15.2. Asthma (p = 0.003) and depression (p = 0.002) were found to be independent predictors of higher SNOT-22 scores. Thirteen articles were identified in the literature search and 1 was provided via author correspondence, with 10 reporting sufficient data to be included in the meta-analysis. Weighted mean SNOT-22 score was 11 ± 9.4 (n = 1517). Our data differed significantly from published data (mean difference = 5.4; 95% confidence interval [CI], 3.4 to 7.5; p < 0.0001) likely owing to differences in comorbidities. SNOT-22 scores vary in non-CRS populations depending upon the group queried. Asthma and depression are associated with higher SNOT-22 scores and should be considered when determining what constitutes a normal value.


Honeybee viruses in Uruguay.
Mortality of honeybees is a serious problem that beekeepers have to face periodically in Uruguay and worldwide. The presence of RNA viruses, in addition to other pathogens may be one of its possible causes. In this work, we detected Chronic bee paralysis virus, Acute bee paralysis virus, Black queen cell virus, Sacbrood virus and Deformed wing virus in samples of Uruguayan honeybees with or without Varroa destructor and Nosema apis. The detection of viruses in different provinces, simultaneous co-infection of colonies by several viruses and the fact that 96% of the samples were infected with one or more virus, indicates they are widely spread in the region.


Unbalanced dendritic inhibition of CA1 neurons drives spatial-memory deficits in the Ts2Cje Down syndrome model.
Overinhibition is assumed one of the main causes of cognitive deficits (e.g. memory impairment) in mouse models of Down syndrome (DS). Yet the mechanisms that drive such exaggerated synaptic inhibition and their behavioral effects remain unclear. Here we report the existence of bidirectional alterations to the synaptic inhibition on CA1 pyramidal cells in the Ts2Cje mouse model of DS which are associated to impaired spatial memory. Furthermore, we identify triplication of the kainate receptor (KAR) encoding gene Grik1 as the cause of these phenotypes. Normalization of Grik1 dosage in Ts2Cje mice specifically restored spatial memory and reversed the bidirectional alterations to CA1 inhibition, but not the changes in synaptic plasticity or the other behavioral modifications observed. We propose that modified information gating caused by disturbed inhibitory tone rather than generalized overinhibition underlies some of the characteristic cognitive deficits in DS.


Over-diagnosed prostate cancer in solid organ recipients: lessons from the last 3 decades.
Prostate cancer (PC) is the most common neoplasia in men. With aging of solid organ transplant recipients (SOTR), its incidence is likely to increase. The aim of this study was to analyze PC screening results retrospectively in renal transplant recipients (RTR), hepatic transplant recipients (HTR) and cardiac transplant recipients (CTR). A retrospective monocentric study of PC diagnosed in renal, hepatic or cardiac transplanted patients since 1989 was performed. All the patients were followed annually by digital rectal examination and prostate serum antigen (PSA) dosage. 57 PC were diagnosed in 1565 SOTR male patients (3.6%): 35 RTR, 15 HTR, and 7 CTR. Standard incidence ratio (SIR) was 41.9. Mean age at the time of diagnosis was 64.5 (60.5-69.2). Mean time between transplantation and PC diagnosis was 95.7 (39.0-139.5) months. Median PSA rate was 7.0 (6.2-13) ng/mL. Clinical stages were T1, T2, and T3, respectively, for 29, 22 and 6 patients. Diagnosis was done by screening in 52 patients, after prostatitis in 1 and bone pain in another. Three PC were discovered on prostate chips after transurethral resection. Two patients were treated by active surveillance. 39 (68%) patients (25 RTR, 11 HTR and 3 CTR) were treated by radical prostatectomy. Histological results were 30 pT2 and 9 pT3 tumors, with 7 positive surgical margins. Gleason score was 5, 6, 7, 8 and 9 in, respectively, in 2, 24, 11, 1 and 1 patients. One patient with positive pelvic nodes was treated with hormonal therapy (HT). One had a biochemical relapse at 10 months and underwent salvage radiotherapy. Median follow-up was 85.2 months (46.1-115.0). 23 (40.4%) patients died. Two (3.6%) RTR and 1 (1.8%) CTR died from their PC. Standard incidence ratio were, respectively, 42.4, 48.2 and 39 in RTR, HTR and CTR. Systematic screening in male SOTR after 50 years old could not be recommended. In the last 3 decades, we diagnosed too many low-risk prostate cancers strongly increasing the SIR but failing to decrease prostate cancer related mortality. SOTR should undergo individual screening with prior MRI when PSA rates are high. Management should not be different from that of the general population.


Carotid Free-Floating Thrombus in a Stent 6 Months After Carotid Artery Stenting.
Carotid free-floating thrombus (CFFT) is defined as a blood clot attached to the arterial wall with surrounding blood flow at its distal component. Although rare, it is a clinically significant cause of embolic stroke. CFFT within a stent has not been previously reported. We report a 64-year-old man who underwent carotid artery stenting for asymptomatic right carotid artery stenosis. Six months after carotid artery stenting, he was admitted to the emergency department 1 hour after onset of left hemiparesis and dysarthria. His National Institutes of Health Stroke Scale score was 10. His medical history was notable for hypertension, chronic renal insufficiency, and type 2 diabetes mellitus. Carotid ultrasonography showed a dumbbell-shaped CFFT attached to the carotid stent that was moving in synchrony with his heartbeat. CFFT removal was performed via an endovascular approach with manual suction using a Luer Lock syringe. The CFFT was completely removed without residual stenosis. Histologic examination suggested plaque rupture associated with a lipid-rich necrotic core. Carotid plaque formation and plaque rupture can occur within a carotid stent and present as a CFFT.


Oral food challenges in children: review and future perspectives.
Food allergy is a lifelong condition with no known treatment or cure. Allergy tests such as skin tests and blood tests are not always accurate when positive and are not necessarily diagnostic of a food allergy. A food allergy takes into consideration both the history of exposure and the testing. The food challenge is considered the diagnostic gold standard for food allergy. However, recent evidence suggests that not enough challenges are being performed. Several techniques exist with which clinicians can challenge patients. Providers who perform challenges should be familiar with assessing signs and symptoms of a potential reaction and must be prepared to treat anaphylaxis. The magnitude of the serum and skin tests may be of assistance in stratifying a patient's risk of passing a challenge, and newer diagnostic tests may help better stratify such risk of based on particular epitope recognition.


Bladder complications in patients receiving cyclophosphamide for systemic lupus erythematosus or rheumatoid arthritis.
The bladder complications of 54 patients treated with oral cyclophosphamide for systemic lupus erythematosus (43) or rheumatoid arthritis (11) were reviewed. During an observation period of 241 patient years, we saw seven cases of acute hemorrhagic cystitis and two cases of transitional cell carcinoma of the bladder. Bladder carcinoma was identified 28 and 60 months after withdrawal of the drug and resulted in the death of one patient. The late-occurring serious toxicities of cyclophosphamide should limit the use of the drug in the treatment of nonmalignant inflammatory rheumatic conditions.


A single-cell transcriptome atlas of glial diversity in the human hippocampus across the postnatal lifespan.
The molecular diversity of glia in the human hippocampus and their temporal dynamics over the lifespan remain largely unknown. Here, we performed single-nucleus RNA sequencing to generate a transcriptome atlas of the human hippocampus across the postnatal lifespan. Detailed analyses of astrocytes, oligodendrocyte lineages, and microglia identified subpopulations with distinct molecular signatures and revealed their association with specific physiological functions, age-dependent changes in abundance, and disease relevance. We further characterized spatiotemporal heterogeneity of GFAP-enriched astrocyte subpopulations in the hippocampal formation using immunohistology. Leveraging glial subpopulation classifications as a reference map, we revealed the diversity of glia differentiated from human pluripotent stem cells and identified dysregulated genes and pathological processes in specific glial subpopulations in Alzheimer's disease (AD). Together, our study significantly extends our understanding of human glial diversity, population dynamics across the postnatal lifespan, and dysregulation in AD and provides a reference atlas for stem-cell-based glial differentiation.


Comparison in the incidence of anorectal malformations between a first- and third-world referral center.
Aim of study was to evaluate the differences in incidence and presentation of anorectal malformations (ARMs) between selected Pediatric Surgery Divisions in the Republic of South Africa (ZAR) and Italy. A retrospective cohort study involved analysis of clinical records of patients with ARM born between 2005 and 2012. Type of ARM, maternal age, birth weight, gestational age, presence of associated anomalies and delayed diagnosis were analyzed. 335 patients were included in this study. Of note, statistically significant differences between the African and European patient groups were observed in a male predominance in the ZAR patient population. In addition, female recto-perineal fistulas were diagnosed in significantly more Italian patients than in ZAR. Furthermore, a more advanced maternal age and a lower gestational age was noted in the European cohort with a minimal delay in initial diagnosis as opposed to the African counterpart. Both centers reported recto-perineal fistula as the most common malformation in male patients. With the exception of perineal fistulas in females, the incidence of specific subtypes of ARMs was similar in the two groups. This may be of importance when extrapolating European study conclusion to the South African setting.


Dicer expression in estrogen receptor-positive versus triple-negative breast cancer: an antibody comparison.
Dicer is an RNase III enzyme responsible for cleaving double-stranded RNAs into small interfering RNAs and microRNAs, which either target messenger RNA transcripts for degradation or inhibit translation. Dicer protein levels have been examined in breast cancer with contradictory results. Our goal was to resolve whether Dicer levels differ in breast cancer versus normal breast epithelium and between estrogen receptor-α-positive (ER+) or estrogen receptor-α-negative (ER-) primary breast cancers. We compared 3 different Dicer antibodies: Abcam 4A6, Abcam ab5818, and Sigma HPA000694, using immunohistochemistry and Western blot analyses. All 3 Dicer antibodies detected higher levels of Dicer in ER+ breast cancer cell lines versus ER-, and all 3 recognized exogenous overexpressed Dicer. In clinical specimens, all 3 antibodies detected higher Dicer in ER+ breast cancers versus triple-negative breast cancer (TNBC) but had very different staining patterns by immunohistochemistry on the same tumor samples. Using the optimal antibody, ab5818, selected for its sensitivity and specificity, Dicer protein expression was significantly higher in ER+ versus TNBC clinical specimens of primary tumor (P<.0001, unpaired t test). Dicer was also significantly higher in adjacent normal breast epithelium versus TNBC (P<.0001, paired t test; n=18 pairs). Differences in antibody performance may explain contrasting results observed in the literature regarding Dicer protein in breast cancer. If Dicer becomes more clinically relevant as a prognostic indicator, further antibody optimization and standardization will be critical.


Mechanisms of Disease: angiogenesis in inflammatory diseases.
Angiogenesis, the development of new vessels, is an important process in health and disease. The perpetuation of neovascularization in inflammatory diseases, such as rheumatoid arthritis, spondyloarthropathies and some systemic autoimmune diseases, might facilitate the ingress of inflammatory cells into the synovium and, therefore, stimulate pannus formation. Disorders associated with perpetuated neovascularization are considered to be angiogenic inflammatory diseases. Several angiogenic mediators, including growth factors, cytokines, matrix metalloproteinases, matrix macromolecules, cell adhesion receptors, chemokines and chemokine receptors, have been implicated in the process of capillary formation. There is a regulatory network in inflamed tissues that is involved in the upregulation or downregulation of angiogenesis. Endogenous angiostatic factors downregulate neovascularization and might act as angiostatic agents. Furthermore, angiogenesis might be targeted by several specific approaches that could be therapeutically used to control inflammatory diseases.


Measuring the prediction of observed actions using an occlusion paradigm: Comparing autistic and non-autistic adults.
Action prediction involves observing and predicting the actions of others and plays an important role in social cognition and interacting with others. It is thought to use simulation, whereby the observers use their own motor system to predict the observed actions. As individuals diagnosed with autism are characterized by difficulties understanding the actions of others and motor coordination issues, it is possible that action prediction ability is altered in this population. This study compared action prediction ability between 20 autistic and 22 non-autistic adults using an occlusion paradigm. Participants watched different videos of a female actor carrying out everyday actions. During each video, the action was transiently occluded by a gray rectangle for 1000 ms. During occlusions, the video was allowed to continue as normal or was moved forward (i.e., appearing to continue too far ahead) or moved backwards (i.e., appearing to continue too far behind). Participants were asked to indicate after each occlusion whether the action continued with the correct timing or was too far ahead/behind. Autistic individuals were less accurate than non-autistic individuals, particularly when the video was too far behind. A trend analysis suggested that autistic participants were more likely to judge too far behind occlusions as being in time. These preliminary results suggest that prediction ability may be altered in autistic adults, potentially due to slower simulation or a delayed onset of these processes. LAY SUMMARY: When we observe other people performing everyday actions, we use their movements to help us understand and predict what they are doing. In this study, we found that autistic compared to non-autistic adults were slightly less accurate at predicting other people's actions. These findings help to unpick the different ways that social understanding is affected in autism.


A case of brief psychosis associated with an arachnoid cyst.
Little is known about the arachnoid cyst and there have been few reports of it accompanying psychiatric disturbances. A 57-year-old patient was admitted due to sudden headache, auditory hallucination, and delusion of persecution. An arachnoid cyst was found in the anteromedial aspect of middle cranial fossa on his magnetic resonance image. This was his first psychotic episode and he was also negative to other clinical evaluations including endocrine system. His psychotic symptoms were suspected to be induced by the arachnoid cyst and it was well controlled by low-dose risperidone administration. He left hospital free from psychotic symptoms on 14th hospital day.


Estimation and comparison of salivary flow rate and its composition in diabetic patients and nondiabetic patients: A pilot study.
Diabetes mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemia irregularities in the metabolism of carbohydrates, lipids and protein. It is often associated with the development of microvascular and macrovascular complications and neuropathies. The health of oral tissues is known to be related to the quality and quantity of saliva both of which may be altered in diabetes. The aim of the present study was to determine the salivary flow rate, electrolytes and total proteins in saliva of Type II diabetic patients. A total number of 120 participants were included in this study, in which 80 patients were suffering from Type II DM (which included both controlled and uncontrolled diabetes) and 40 nondiabetic persons (controls). The study population included both the genders, with an age range of 40-70 years. The study population was divided into three groups. The values of total protein, sodium, potassium and salivary flow rate among controls, controlled diabetes and uncontrolled diabetes were collected, formulated and multiple comparisons between the groups using the analysis of variance and post hoc Tukey honestly significant difference analysis were done in version 16.0 of SPSS software. Studies with larger sample size are warranted to know the exact pathophysiology of controlled and uncontrolled Type II DM in terms of salivary flow rate, salivary electrolytes and total protein.


Epiretinal membrane surgery with or without internal limiting membrane peeling.
The purpose of the present paper was to evaluate the visual outcome and recurrence rate of epiretinal membrane (ERM) formation following vitreoretinal surgery with and without internal limiting membrane (ILM) peel. The medical records of 42 consecutive patients who underwent surgery for macular ERM by a single surgeon were reviewed. All patients underwent pars plana vitrectomy and ERM removal with a subset undergoing ILM peel. Recurrence of macular ERM within 18 months and the final visual outcome after surgery were compared between patients with and without ILM removal. Twenty-five patients (59.5%) underwent ERM surgery with ILM peeling and 17 patients (40.5%) underwent ERM surgery without ILM peeling. The mean preoperative logMAR visual acuity was 0.77 and 0.96 for the ILM peeling and non-ILM peeling groups, respectively. Visual acuity improved significantly in both the ILM and non-ILM peeling groups after ERM surgery (P < 0.001 and P = 0.003, respectively). Eighteen months after surgery, 3/17 eyes without ILM peeling (17.6%) developed recurrent macular ERM, compared with none of the 25 eyes with ILM peeling (log-rank test, P = 0.030). Internal limiting membrane removal during macular ERM surgery may minimize the recurrence of ERM, without adverse visual outcome. Further controlled prospective studies are needed to determine the role of ILM peeling in ERM surgery.


Uptake and urinary excretion of aluminum among welders.
The urinary excretion of aluminum was measured in 23 welders before and after an exposure-free interval of 16 to 37 days. In addition, the concentration of aluminum in the air was measured at the work site of 16 aluminum welders on the same workday as the first urine sample was taken. The concentration of aluminum in the urine depended on both the level and duration of exposure. The postshift urinary concentration of aluminum prior to an exposure-free interval was mainly related to the current air concentration, whereas the urinary concentration of aluminum determined after the exposure-free interval was related to total exposure duration (years). Among welders exposed for less than 1 year, the half-time for urinary concentration was about 9 days whereas welders exposed for more than 10 years had half-times calculated to be 6 months or longer. The results indicate that aluminum is retained and stored in at least two functional compartments of the body and is eliminated from these compartments at different rates.


Possible neural substrates for orientation analysis and perception.
Recent research into the response properties of extrastriate visual cortical mechanisms has revealed single-cell functional organisation which closely parallels certain global and apparently emergent properties of psychophysical observation. An attempt is made to relate previous data on orientation illusions and aftereffects to these extrastriate mechanisms and new data which cannot be explained adequately by V1 (striate) orientation channels are discussed. Conversely, properties of cells in areas such as V3, V4, MT, and others seem to provide an obvious neural substrate for global interactions. It is suggested that psychological 'explanations' couched in terms of 'hypotheses' or 'cognitive problem solving' lack heuristic value, and that, in contrast, the properties of extrastriate cells can suggest novel experimental psychophysical paradigms which are designed to probe these higher-order global mechanisms more or less selectively.


Poststreptococcal keratouveitis associated with group C streptococcus pharyngitis.
To report the first case of poststreptococcal syndrome uveitis (PSU) in association with group C streptococcus (GCS). Chart review of a 24-year-old man who presented with bilateral ocular redness, pain, and photophobia for 5 days and "white rings" around his eyes for a duration of 3 days. The patient further reported fever and sore throat in the preceding week. Slit-lamp examination showed bilateral keratouveitis. A thorough uveitis workup, antistreptolysin O (ASLO) titer, and throat culture were obtained. The patient was treated with frequent topical steroids and systemic doxycycline. The uveitis and keratitis subsided over the next few weeks, leaving extensive peripheral keratolysis. The results of laboratory diagnostic testing revealed an elevated ASLO, C-reactive protein, as well as HLA-B27 positivity. Throat cultures grew beta-hemolytic GCS; group A streptococcus was culture negative. GCS pharyngitis may be a causative organism of PSU.


Effectiveness and tolerability of neoadjuvant pertuzumab-containing regimens for HER2-positive localized breast cancer.
Based on improvement in pathologic complete response (pCR) in the NeoSphere and TRYPHAENA studies, the FDA approved neoadjuvant pertuzumab for HER2+ localized breast cancer. These studies demonstrated high pCR rates with THP (docetaxel + HP), FEC (5-fluorouracil, epirubicin, and cyclophosphamide)-THP, and TCHP (docetaxel, carboplatin + HP). However, in the United States, doxorubicin/cyclophosphamide (AC) is favored over FEC despite no data comparing neoadjuvant AC-THP with AC-TH or TCHP. Here we report outcomes for patients with localized HER2+ breast cancer treated with pertuzumab-containing neoadjuvant regimens and AC-TH. We reviewed clinicopathological characteristics of patients with HER2+ breast cancer (Stage I-III) treated with either a neoadjuvant pertuzumab-containing regimen or dose-dense (dd) AC-TH, from 2011 to 2016 at a large academic medical institution and two affiliated community sites. pCR was defined as ypT0/is ypN0. Fisher's exact test and logistic regression analysis were used for statistical analysis. In this study (N = 121), pCR was numerically higher with pertuzumab-based regimens, including ddAC-THP (60%), TCHP (63%), THP (55%), as compared with ddAC-TH (46%). THP resulted in significantly less cycle delays due to toxicity compared to the other regimens (p = 0.02). THP also resulted in the least dose reductions, lowest rate of hospitalization, and lowest rate of treatment discontinuation. Pertuzumab-based regimens, including THP, resulted in higher pCR rates as compared to ddAC-TH, with the THP regimen associated with the best tolerability among patients with localized HER2+ breast cancer. Given the various neoadjuvant regimens, additional studies are needed to determine optimal treatment sequencing and escalation/de-escalation strategies to personalize neoadjuvant regimens for localized HER2+ breast cancer.


Lacrimal intubation in the primary repair of midfacial fractures.
Midfacial trauma causes a variety of functional and cosmetic problems that concern many surgical specialties. Fractures of the lacrimal sac fossa and lacrimal canal and compromise of the intrinsic membranous pathways are frequently not addressed, requiring late lacrimal bypass surgery in many cases. Silicone intubation of 11 disrupted distal pathways was performed as part of the primary, interdisciplinary repair of midfacial fractures. Revision of two systems was necessitated by later surgery performed for unrelated problems. In the remaining nine primarily intubated systems, patency was maintained in long-term follow-up. The role of the ophthalmic surgeon in the recognition and primary intubation of fractured distal lacrimal pathways should be stressed among colleagues in otolaryngology, plastic surgery, and maxillofacial surgery.


[Astigmatism after keratoplasty: influence of orthotopic transplantation].
Patients undergoing corneal transplantation often suffer from postoperative reduced vision due to high astigmatism. This retrospective study analyzed the influence of heterotopic or orthotopic transplantation on astigmatism and visual outcome. In this study 373 eyes of 334 patients were analyzed. Group 1 (OT) contained 186 eyes, which underwent orthotopic transplantation (side of recipient and donor corresponded), whereas group 2 (HT) included 187 heterotopic keratoplasties (donor cornea placed in the recipient's contralateral side). After 1, 3, 6, 12 and 24 months the median of keratometric astigmatism, objective astigmatism, topographic astigmatism and best corrected visual acuity (BCVA) were assessed and compared between groups. The long-term results showed no statistically significant differences regarding keratometric and objective astigmatism, whereas topographic astigmatism differed significantly (p = 0.04) after 3 months. We observed a lower astigmatism of 5.7 dpt (range 3.08-7.78 dpt) in group OT than in the group HT with 7.1 dpt (range 3.9-10.7 dpt). No differences were found at the other time points. The BCVA showed a significantly better effect after 1 month (p = 0.01) in the OT group of 0.2 (0.1-0.3) than in HT group of 0.1 (0.05/0.25). In the postoperative course no additional significant dissimilarities were documented. Heterotopic and orthotopic keratoplasty show no significant long-term differences in astigmatism and visual outcom.


Probing the tunnelling site of electrons in strong field enhanced ionization of molecules.
Molecules show a much increased multiple ionization rate in a strong laser field as compared with atoms of similar ionization energy. A widely accepted model attributes this to the action of the joint fields of the adjacent ionic core and the laser on its neighbour inside the same molecule. The underlying physical picture for the enhanced ionization is that it is the up-field atom that gets ionized. However, this is still debated and remains unproven. Here we report an experimental verification of this long-standing prediction. This is accomplished by probing the two-site double ionization of ArXe, where the instantaneous field direction at the moment of electron release and the emission direction of the correlated ionizing centre are measured by detecting the recoil sum- and relative-momenta of the fragment ions. Our results unambiguously prove the intuitive picture of the enhanced multielectron dissociative ionization of molecules and clarify a long-standing controversy.


[Resistant hypertension and chronic kidney disease: epidemiology and prognosis].
The emergence of new effective therapeutic strategies for the treatment of resistant hypertension such as renal sympathetic denervation technique has lead to a renewed interest in the screening and assessment of prognosis of this specific entity which constitutes a subset of uncontrolled hypertension. Its prevalence is unknown, but estimated between 12 and 15% among hypertensive subjects from the general population. Several factors have been associated with the development of resistant hypertension, four of which are essential: age, diabetes, chronic kidney disease and vascular structural alteration. Excessive salt intake is also a risk factor for poorly controlled hypertension in patients with salt-dependent hypertension, and may participate to the genesis of resistant hypertension. Because of population ageing and increasing prevalence of diabetes, obesity and chronic kidney disease, the prevalence of resistant hypertension is expected to rise. A better understanding of its determinants and associated risks (such as chronic kidney disease) would identify high-risk groups that may benefit from extensive diagnosis work up and more specific treatments.


Initiation and engagement as mechanisms for change caused by collaborative care in opioid and alcohol use disorders.
To assess the mechanism by which a collaborative care (CC) intervention improves self-reported abstinence among primary care patients with opioid and alcohol use disorders (OAUD) compared to treatment as usual. Secondary data analysis of SUMMIT, a randomized controlled trial of CC for OAUD. Participants were 258 patients with OAUD receiving primary care at a multi-site Federally Qualified Health Center. Using a mediation analysis decomposition of a total effect into a mediated and a direct effect, we examined the effect of CC on abstinence at six months, attributable to the HEDIS treatment initiation and engagement measures for the total sample, for individuals with alcohol use disorders alone, and for those with a co-morbid opioid use disorder. Although the CC intervention led to an increase in both initiation and engagement, among the full sample, only initiation mediated the effect of the intervention on abstinence (3.8%, CI=[0.4%, 8.3%]; 32% proportion of the total effect). In subgroup analyses, among individuals with comorbid alcohol and opioid use disorders, almost 100% of the total effect was mediated by engagement, but the effect was not significant. This was not observed among the alcohol use disorder only group. Among primary care patients with OAUDs, treatment initiation partially mediated the effect of CC on abstinence at 6-months. The current study emphasizes the importance of primary care patients returning for a second substance-use related visit after identification. CC may work differently for people with co-morbid opioid use disorders vs. alcohol use disorders alone.


Tumor regression following intravenous administration of lactoferrin- and lactoferricin-bearing dendriplexes.
The possibility of using gene therapy for the treatment of cancer is limited by the lack of safe, intravenously administered delivery systems able to selectively deliver therapeutic genes to tumors. In this study, we investigated if the conjugation of the polypropylenimine dendrimer to lactoferrin and lactoferricin, whose receptors are overexpressed on cancer cells, could result in a selective gene delivery to tumors and a subsequently enhanced therapeutic efficacy. The conjugation of lactoferrin and lactoferricin to the dendrimer significantly increased the gene expression in the tumor while decreasing the non-specific gene expression in the liver. Consequently, the intravenous administration of the targeted dendriplexes encoding TNFα led to the complete suppression of 60% of A431 tumors and up to 50% of B16-F10 tumors over one month. The treatment was well tolerated by the animals. These results suggest that these novel lactoferrin- and lactoferricin-bearing dendrimers are promising gene delivery systems for cancer therapy. Specific targeting of cancer cells should enhance the delivery of chemotherapeutic agents. This is especially true for gene delivery. In this article, the authors utilized a dendrimer-based system and conjugated this with lactoferrin and lactoferricin to deliver anti-tumor genes. The positive findings in animal studies should provide the basis for further clinical studies.


A multicaloric cooling cycle that exploits thermal hysteresis.
The giant magnetocaloric effect, in which large thermal changes are induced in a material on the application of a magnetic field, can be used for refrigeration applications, such as the cooling of systems from a small to a relatively large scale. However, commercial uptake is limited. We propose an approach to magnetic cooling that rejects the conventional idea that the hysteresis inherent in magnetostructural phase-change materials must be minimized to maximize the reversible magnetocaloric effect. Instead, we introduce a second stimulus, uniaxial stress, so that we can exploit the hysteresis. This allows us to lock-in the ferromagnetic phase as the magnetizing field is removed, which drastically removes the volume of the magnetic field source and so reduces the amount of expensive Nd-Fe-B permanent magnets needed for a magnetic refrigerator. In addition, the mass ratio between the magnetocaloric material and the permanent magnet can be increased, which allows scaling of the cooling power of a device simply by increasing the refrigerant body. The technical feasibility of this hysteresis-positive approach is demonstrated using Ni-Mn-In Heusler alloys. Our study could lead to an enhanced usage of the giant magnetocaloric effect in commercial applications.


Continuous Tuning of Au-Cu2 O Janus Nanostructures for Efficient Charge Separation.
In photocatalysis, the Schottky barrier in metal-semiconductor hybrids is known to promote charge separation, but a core-shell structure always leads to a charge build-up and eventually shuts off the photocurrent. Here, we show that Au-Cu2 O hybrid nanostructures can be continuously tuned, particularly when the Cu2 O domains are single-crystalline. This is in contrast to the conventional systems, where the hybrid configuration is mainly determined by the choice of materials. The distal separation of the Au-Cu2 O domains in Janus nanostructures leads to enhanced charge separation and a large improvement of the photocurrent. The activity of the Au-Cu2 O Janus structures is 5 times higher than that of the core-shell structure, and 10 times higher than that of the neat Cu2 O nanocubes. The continuous structural tuning allows to study the structure-property relationship and an optimization of the photocatalytic performance.


Pigment epithelium-derived factor increases in type 2 diabetes after treatment with metformin.
Pigment epithelium-derived factor (PEDF) has anti-angiogenic, immunomodulatory and anti-inflammatory properties. In addition to the significant role it plays in reducing diabetic complications, PEDF is now used in the treatment of certain cancers. It possibly plays a role in insulin resistance cases, too. However, whether metformin treatment has any significant effects on PEDF levels is not known. In this study, we investigated the regulation of PEDF in type 2 diabetes in relation to fat mass and insulin resistance before and after the use of metformin for treatment. Prospective cohort study. Thirty-six patients with newly diagnosed type 2 diabetes and 33 healthy individuals. Baseline weight, waist circumference (WC), fasting (FPG) and postprandial (PPPG) glucose, insulin, HbA1c, HOMA, PEDF and total/truncal fat mass were determined both in the diabetic and control subjects. Procedures were repeated in the diabetic group after a 6-month metformin treatment. Baseline FPG, PPPG, HbA1c, HOMA, weight, WC and truncal fat mass were higher in patients with diabetes whereas PEDF levels were found to be comparable with the controls. We completed the study with 31 of the 36 patients with diabetes we had selected for the study. We observed a decrease in the weight, WC, FPG, PPPG, HOMA, total and truncal fat mass of the patients while there was a significant rise in the PEDF levels (P = 0·002) after the metformin treatment. On the other hand, no significant correlation was observed between the change in PEDF levels and the clinical and laboratory findings. Our study is the first to identify a metformin-related increase in PEDF levels in diabetes. The increase observed in PEDF levels after the metformin treatment does not seem to be related to the changes in insulin resistance, fat mass or glycemic control. Hence, our results suggest that further investigation is necessary to determine the direct effects of metformin on PEDF gene and protein expression in vitro.


Determination of mycotoxins and their dietary exposure assessment in pale lager beers using immunoaffinity columns and UPLC-MS/MS.
The use of contaminated raw materials can lead to the transfer of mycotoxins into the final product, including beer. This study describes the use of the commercially available immunoaffinity column 11+Myco MS-PREP® and UPLC-MS/MS for the determination of mycotoxins in pale lager-type beers brewed in Czech Republic and other European countries. The additional aim of the work was to develop, optimize and validate this analytical method. Validation parameters such as linearity, limit of detection (LOD), limit of quantification (LOQ), precision and accuracy were tested. The calibration curves were linear with correlation coefficients (R2 > 0.99) for all mycotoxins under investigation. The LOD ranged from 0.1 to 50 ng/L and LOQ from 0.4 to 167 ng/L. Recoveries of the selected analytes ranged from 72.2 to 101.1%, and the relative standard deviation under conditions repeatability (RSDr) did not exceed 16.3% for any mycotoxin. The validated procedure was successfully applied for the analysis of mycotoxins in a total of 89 beers from the retail network. The results were also processed using advanced chemometric techniques and compared with similar published studies. The toxicological impact was taken into account.


The Hoffer Q formula: a comparison of theoretic and regression formulas.
A new formula, the Hoffer Q, was developed to predict the pseudophakic anterior chamber depth (ACD) for theoretic intraocular lens (IOL) power formulas. It relies on a personalized ACD, axial length, and corneal curvature. In 180 eyes, the Q formula proved more accurate than those using a constant ACD (P < .0001) and equal (P = .63) to those using the actual postoperative measured ACD (which is not possible clinically). In 450 eyes of one style IOL implanted by one surgeon, the Hoffer Q formula was equal to the Holladay (P = .65) and SRK/T (P = .63) and more accurate than the SRK (P < .0001) and SRK II (P = .004) regression formulas using optimized personalization constants. The Hoffer Q formula may be clinically more accurate than the Holladay and SRK/T formulas in eyes shorter than 22.0 mm. Even the original nonpersonalized constant ACD Hoffer formula compared with SRK I (using the most valid possible optimized personal A-constant) has a better mean absolute error (0.56 versus 0.59) and a significantly better range of IOL prediction error (3.44 diopters [D] versus 7.31 D). The range of error of the Hoffer Q formula (3.59 D) was half that of SRK I (7.31 D). The highest IOL power errors in the 450 eyes were in the SRK II (3.14 D) and SRK I (6.14 D); the power error was 2.08 D using the Hoffer Q formula. The series using overall personalized ACD was more accurate than using an axial length subgroup personalized ACD in each axial length subgroup. The results strongly support replacing regression formulas with third-generation personalized theoretic formulas and carefully evaluating the Holladay, SRK/T, and Hoffer Q formulas.


Detection of small vessels with electron beam computed tomographic angiography using 1.5 and 3 mm collimator protocols.
To evaluate the effect of scanner collimation on the ability to detect small cardiac vessels using electron beam CT coronary angiography (EBA). EBA scans from 40 patients who underwent study on two separate occasions with 3 mm (initial scan) and 1.5 mm (follow-up scan) collimation protocols were analyzed. Vessels of <2 mm in diameter were identified. The 1.5 mm collimation allowed 3-D visualization of 129 vessels<2 mm in diameter, while 3 mm collimation only allowed visualization of 89 vessels (p<0.001). The right coronary artery branches and distal LAD segments though were not displayed satisfactorily in almost half of the 3-D studies with either protocol. There was significant improvement in detection of small cardiac vessels with a 1.5 mm collimation EBA protocol compared to a 3 mm protocol. Both protocols though were insufficient for reliable visualization of the right coronary artery branches and distal LAD segments.


Lipophilicity and transporter influence on blood-retinal barrier permeability: a comparison with blood-brain barrier permeability.
To determine the lipophilicity trend line from the relationship between the blood-retinal barrier (BRB) permeability and the lipophilicity of permeants and compare it with that of the blood-brain barrier (BBB). The retinal (RUI) and brain uptake index (BUI) of 26 radiolabeled compounds across the rat BRB and BBB, respectively, were measured using the carotid artery injection method. RUI was determined using 13 compounds expected to be transported from blood to the retina by passive diffusion and with a log n-octanol/Ringer distribution coefficient (DC) ranging from -2.56 to 2.48. The RUI values were correlated with the log of the DC [RUI = 46.2 × exp (0.515 × log DC), r(2) = 0.807]. A similar trend was obtained between BUI and lipophilicity. The RUI value for substrates of the influx transporters and P-glycoprotein (P-gp) was greater and smaller than the lipophilicity trend line, respectively. In contrast, [(3)H]verapamil, which is a substrate of P-gp, has a greater RUI value than the lipophilicity trend line, but not for BUI, suggesting that the BRB has an influx transport system for verapamil. The lipophilicity trend line constructed from the RUI and DC values is considered to reflect the transport properties of drugs undergoing passive diffusion across the BRB.


An improved protocol for generation and characterization of human-induced pluripotent stem cell-derived retinal pigment epithelium cells.
We present an optimized protocol for guided differentiation of retinal pigment epithelium (RPE) cells from human-induced pluripotent stem cells (iPSC). De novo-generated RPE cells are mature, polarized, and mimic the cellular and molecular profile of primary RPE; they are also suitable for in vivo cell transplantation studies. The protocol includes an enrichment step, making it useful for large-scale GMP manufacturing. RPE cells produced following this protocol are appropriate for cell replacement therapy for macular degeneration and disease modeling. For complete details on the use and execution of this protocol, please refer to Surendran et al. (2021).


Development of new models for the analysis of Fc-FcRn interactions.
An important question remains as to which FcRn binding parameters, if any, correlate with the serum half-life of antibodies. In the present study, we used a BIACore surface plasmon resonance (SPR) device to study kinetic properties of antibody binding to FcRn at different pHs and under different binding reaction conditions. The ability of many different models to fit the data was tested. The previous models could not adequately explain all of the data collected. We now present models that have intuitive appeal and fit a broader range of data than previous models. Specifically, the model assumes that there are two forms of FcRn on the BIAcore chip and that, in addition to monomeric IgG, there is some aggregated IgG that can function as ligand. Although this model represents an improvement over previous models, it is still not globally valid for the entire range of data that was collected. Even with these limitations, the model provides a powerful new tool to analyze not only FcRn-IgG interactions but also other complex protein-protein interactions.


Effect of day of the week on short- and long-term mortality after emergency general surgery.
The effect of day of the week on outcome after surgery is the subject of debate. The aim was to determine whether day of the week of emergency general surgery alters short- and long-term mortality. This was an observational study of all patients undergoing emergency general surgery in Scotland between 1 January 2005 and 31 December 2007, followed to 2012. Multilevel logistic and Cox proportional hazards regression were used to assess the effect of day of the week of surgery on outcome after adjustment for case mix and risk factors. The primary outcome was perioperative mortality; the secondary outcome was overall survival. A total of 50 844 patients were identified, of whom 31 499 had an emergency procedure on Monday to Thursday and 19 345 on Friday to Sunday. Patients undergoing surgery at the weekend were younger (mean 45·9 versus 47·5 years; P < 0·001) and had fewer co-morbidities, but underwent riskier and/or more complex procedures (P < 0·001). Patients who had surgery at the weekend were more likely to have been operated on sooner than those who had weekday surgery (mean time from admission to operation 1·2 versus 1·6 days; P < 0·001). No difference in perioperative mortality (odds ratio 1·00, 95 per cent c.i. 0·89 to 1·13; P = 0·989) or overall survival (hazard ratio 1·01, 0·97 to 1·06; P = 0·583) was observed when surgery was performed at the weekend. There was no difference in overall survival after surgery undertaken on any particular day compared with Wednesday; a borderline reduction in perioperative mortality was seen on Tuesday. There was no difference in short- or long-term mortality following emergency general surgery at the weekend, compared with mid-week.


Blood irradiator dosimetry with BANG polymer gels.
Transfusion-associated graft-versus-host disease is believed to be a preventable complication of blood transfusion in susceptible high-risk patients. Irradiation of allogeneic blood components is considered to be a safe and effective method inhibiting the proliferative capacity of lymphocytes. Physical factors that influence dose delivery include source and sample geometry, homogeneity of the dose distribution within the irradiation volume, and factors that influence dose absorption within the sample. Polymer gel dosimetry was used to evaluate the three-dimensional dose distribution for blood bags, platelet (PLT) bags, and syringes in typical geometries. The qualitative dose distribution within a cylindrical phantom determined with the polymer gel was in good agreement with the distribution in water determined with a DOSE-MAP film dosimetry system. Dose uniformity in blood bags and syringes was acceptable. Low signal strength and volume averaging hamper determination of the dose in PLT bags. Geometrical considerations in routine blood product irradiation may be evaluated with the use of polymer gel dosimetry. The procedures, however, are highly technical and are susceptible to low signal-to-noise and volume averaging considerations under certain geometrical configurations. Under clinical conditions, a reasonably uniform dose can be delivered to blood and blood components in a freestanding irradiator.


Beneficial effects of hypotaurine supplementation in preparation and freezing media on human sperm cryo-capacitation and DNA quality.
Although widely used, slow freezing considerably modifies the functions of human spermatozoa. Cryopreservation induces nuclear sperm alterations and cryo-capacitation, reducing the chances of pregnancy. Hypotaurine is naturally present in the male and female genital tracts and has capacitating, osmolytic and anti-oxidant properties. The analysis were performed on surplus semen of men with normal (n = 19) or abnormal (n = 14) sperm parameters. Spermatozoa were selected by density gradient centrifugation before slow freezing. For each sample, these steps were performed in parallel with ("H+" arm) or without ("H-" arm) hypotaurine supplementation. After thawing, we measured total and progressive mobility, vitality, acrosome integrity, markers of capacitation signaling pathway and nuclear quality. For the latter, we focused on sperm chromatin packaging, DNA fragmentation and the presence of vacuoles in the sperm nucleus. Post-thaw spermatozoa selected and frozen in the presence of hypotaurine had a higher vitality (+ 16.7%, p < 0.001), progressive and total motility (+ 39.9% and + 21.6% respectively, p < 0.005) than spermatozoa from the control "H-" arm. Hypotaurine also reduced the non-specific phosphorylation of the capacitation protein markers P110 and P80 (p < 0.01), indicating a decrease in cryo-capacitation. Hypotaurine supplementation reduced chromatin decondensation, measured by chromomycin A3 (- 16.1%, p < 0.05), DNA fragmentation (- 18.7%, p < 0.05) and nuclear vacuolization (- 20.8%, p < 0.05). Our study is the first to demonstrate beneficial effects of hypotaurine supplementation in preparation and freezing procedures on human spermatozoa sperm fertilization capacity and nucleus quality. Hypotaurine supplementation limited cryo-capacitation, increased the proportion of live and progressively motile spermatozoa and reduces the percentage of spermatozoa showing chromatin decondensation, DNA fragmentation and nuclear vacuolation. Clinical Trial, NCT04011813 . Registered 19 May 2019 - Retrospectively registered.


Exposing the disability-related hidden curriculum in case-based learning: A qualitative study.
People with disabilities face significant health disparities. Studies show that healthcare professionals harbor negative attitudes towards disability, compromising the quality of care. These attitudes, in unwritten, unofficial, and even unintended ways can be passed from providers to learners in the medical education setting. Using a Critical Disability Studies (CDS) paradigm, the authors uncovered the disability-related hidden curriculum within Case-Based Learning (CBL) and proposed guidelines for promoting a disability-conscious medical education that resists ableism. The study team conducted a qualitative analysis of all CBL cases from the pre-clerkship curriculum (n = 53) at Sidney Kimmel Medical College. The authors employed a directed content analysis approach to develop a codebook based on case examination, literature review, and CDS concepts. Two researchers coded all cases and assessed intercoder reliability. The results informed the development of an explanatory model. Only four of 53 cases overtly mentioned disability, none of which defined disability according to CDS. Coding did not identify content challenging stereotypical views of disability. Additionally, two cases included content fueling negative attitudes of disability. By inadequately addressing disability from a CDS perspective, harmful assumptions of disability may go unchallenged, driving a hidden curriculum within CBL. This phenomenon leaves medical students ill-prepared to care for people with disabilities and creates physicians ill-equipped to teach the next generation. Since many health professions utilize CBL to educate students, these cases provide an untapped opportunity to resist ableism and better prepare students to address the negative attitudes driving health disparities experienced by people with disabilities.


Natural components in sunscreens: Topical formulations with sun protection factor (SPF).
Artificial sunscreens are already gaining traction in order to protect the skin from sunburns, photoaging and photocarcinogenesis. However, the efficacy and safety of most artificial sunscreen constituents are hindered by their photostability, toxicity and damage to marine ecosystems. Natural selection and evolution have ensured that plants and animals have developed effective protective mechanisms against the deleterious side effects of oxidative stress and ultraviolet radiation (UV). Hence, natural antioxidants such as sun blockers are drawing considerable attention. The exact mechanism by which natural components act as sunscreen molecules has not been clearly established. However, conjugated π system is reported to play an important role in protecting the vital genetic material within the organism. Compared to artificial sunscreens, natural sunscreens with strong UV absorptive capacities are largely limited by low specific extinction value and by their inability to spread in large-scale sunscreen cosmetic applications. Previous studies have documented that natural components exert their photoprotective effects (such as improved skin elasticity and hydration, skin texture, and wrinkles) through their antioxidant effects, and through the regulation of UV-induced skin inflammation, barrier impairment and aging. This review focuses on natural antioxidant topical formulations with sun protection factor (SPF). Lignin, melanin, silymarin and other ingredients have been added to high sun protection nature sunscreens without any physical or chemical UV filters. This paper also provides a reference for adopting novel technical measures (extracting high content components, changing the type of solution, optimizing formulation, applying Nano technology, et al) to design and prepare nature sunscreen formulations equated with commercial sunscreen formulations. Another strategy is to add natural antioxidants from plants, animals, microorganisms and marine organisms as special enhancer or modifier ingredients to reinforce SPF values. Although the photoprotective effects of natural components have been established, their deleterious side effects have not been elucidated.


Laser-assisted cerebrospinal fluid leak repair: an animal model to test feasibility.
To test the feasibility of laser tissue welding as a method of creating an endonasal tissue bond for the purpose of cerebrospinal fluid leak repair. An 808 nm diode laser was used with a 42% albumin solder to create laser welds in sheep nasal septal mucosa, periosteum, and in situ rabbit maxillary sinus mucosa. Each condition was tested five times. Groups were compared with Kruskal-Wallis nonparametric analysis of variance (ANOVA) and post-hoc multiple-comparisons testing with the Bonferroni test. The burst pressures of sheep septal mucosa (34.88 +/- 3.49 mmHg) and periosteum (30.02 +/- 2.23 mmHg) were significantly higher than suture repair. A burst pressure of 69.58 +/- 2.85 mmHg was achieved in rabbit in situ maxillary sinus mucosa. Laser welding is capable of producing tissue bonds whose burst strength exceeds that of human intracranial pressure. This is the first study to examine the feasibility of laser tissue welding in endonasal tissues. The ability to produce instant transnasal tissue bonds with burst pressures that exceed human intracranial pressure make this technology ideal for cerebrospinal fluid leak repair.


Atomic layer deposition SiO2 films over dental ZrO2 towards strong adhesive to resin.
Atomic layer deposition (ALD) is a self-limiting nanoscale film deposition technology with the advantages of good stability, consistency and conformability. In this study, we proposed to deposit silica (SiO2) films over dental zirconium-oxide (ZrO2) by ALD for better SiO2 films and higher bond strength between ZrO2 and resin. To investigate the superiority of film deposited by ALD, other surface modification methods such as sol-gel, vapor phase hydrolysis and electrostatic self-assembly were compared in terms of the short-term and long-term bond strength between ZrO2 and resin, measured by universal testing machine. Meanwhile, the surface morphology and chemical elemental analysis were characterized by scanning electron microscopy (SEM), energy dispersive spectrometer (EDS) and Fourier transform infrared spectroscopy (FTIR). Results showed that the SiO2 films deposited by ALD or electrostatic self-assembly were uniform and consistent while sol-gel and vapor phase hydrolysis formed SiO2 films with cracks or pores, changing the morphology of ZrO2. ALD had the best results among all methods and increased the bond strength to 16.49 ± 1.60 MPa and 13.44 ± 1.63 MPa before and after aging respectively, which is expected to improve the long-term success rate of clinical dental ZrO2 prostheses.


Identification of bioactive metabolites using activity metabolomics.
The metabolome, the collection of small-molecule chemical entities involved in metabolism, has traditionally been studied with the aim of identifying biomarkers in the diagnosis and prediction of disease. However, the value of metabolome analysis (metabolomics) has been redefined from a simple biomarker identification tool to a technology for the discovery of active drivers of biological processes. It is now clear that the metabolome affects cellular physiology through modulation of other 'omics' levels, including the genome, epigenome, transcriptome and proteome. In this Review, we focus on recent progress in using metabolomics to understand how the metabolome influences other omics and, by extension, to reveal the active role of metabolites in physiology and disease. This concept of utilizing metabolomics to perform activity screens to identify biologically active metabolites - which we term activity metabolomics - is already having a broad impact on biology.


MrNomogram: a web-based multivariable pediatric renal nomogram.
Multivariable Pediatric Renal Nomogram, or MrNomogram, is a web-based clinical tool for the evaluation of pediatric renal length. Unlike other available age-adjusted renal nomograms, MrNomogram takes into consideration the fact that the renal length is influenced by multiple demographic variables. It provides a more accurate prediction of pediatric renal length, given the patient's demographic characteristics, such as age, gender, height, etc. ( https://www.prevmed.sunysb.edu/jjc/MrNomogram).


Serological and molecular diagnosis of human brucellosis in Najran, Southwestern Saudi Arabia.
This study aimed to investigate the prevalence of human brucellosis in Najran, southwestern Saudi Arabia, and to assess the performances of ELISA and PCR as diagnostic tools for brucellosis with respect to conventional methods. The study included 340 patients with clinical characteristics of brucellosis. Blood samples from cases and controls were subjected to culture, standard tube agglutination test (SAT), ELISA for IgM and IgG, and brucella PCR. The diagnosis of brucellosis was confirmed in 54 (15.9%) of the 340 provisionally diagnosed brucellosis patients. Blood culture identified only 14 (25.9%) cases. The SAT was positive for 50 (92.6%) cases, whereas ELISA IgM, IgG and PCR were found positive in 46, 52 and 38 cases respectively. The sensitivities of ELISA IgM and IgG were 85.2% and 96.3% respectively and the specificity was 100% for each. For PCR, the sensitivity and specificity were 70.4% and 100% respectively. In conclusion, ELISA offers a significant advantage over conventional serological methods in the diagnosis of brucellosis in endemic areas. The PCR test results can be particularly important in patients with clinical signs and symptoms, and negative serological results, allowing the early and rapid confirmation of the brucellosis.


Binding specificity of monoclonal antibodies towards fragments of human growth hormone produced by plasmin digestion.
To help define the immunological epitopes on human growth hormone (hGH), interaction of fragments of the hormone with 7 monoclonal antibodies (McAbs) was studied. Plasmin-digested hGH, containing two peptides (hGH1-134 and hGH141-191) joined by a disulphide bond, bound to each McAb with affinity similar to that of intact hGH. The purified C-terminal fragment, hGH141-191, showed low affinity for each McAb. The N-terminal fragment, hGH1-134, bound with quite high affinity to 2 McAbs (EB1 and EB3) but not to the other 5. We conclude that residues 1-134 of hGH contain the epitope to which McAbs EB1 and EB3 bind.


Accurate assessment of the lung sliding artefact on lung ultrasonography using a deep learning approach.
Pneumothorax is a potentially life-threatening condition that can be rapidly and accurately assessed via the lung sliding artefact generated using lung ultrasound (LUS). Access to LUS is challenged by user dependence and shortage of training. Image classification using deep learning methods can automate interpretation in LUS and has not been thoroughly studied for lung sliding. Using a labelled LUS dataset from 2 academic hospitals, clinical B-mode (also known as brightness or two-dimensional mode) videos featuring both presence and absence of lung sliding were transformed into motion (M) mode images. These images were subsequently used to train a deep neural network binary classifier that was evaluated using a holdout set comprising 15% of the total data. Grad-CAM explanations were examined. Our binary classifier using the EfficientNetB0 architecture was trained using 2535 LUS clips from 614 patients. When evaluated on a test set of data uninvolved in training (540 clips from 124 patients), the model performed with a sensitivity of 93.5%, specificity of 87.3% and an area under the receiver operating characteristic curve (AUC) of 0.973. Grad-CAM explanations confirmed the model's focus on relevant regions on M-mode images. Our solution accurately distinguishes between the presence and absence of lung sliding artefacts on LUS.


The variability of urographic findings in posterior urethral valves.
The full variety of secondary and associated upper tract abnormalities concurrent with obstructive valves seems not to be generally appreciated. While upper urinary dilatation and impaired renal function are features regarded as almost obligatory, there are cases at the other end of the spectrum with surprisingly slight or no abnormalities of the bladder, ureters or collecting systems. Therefore a negative IVP does not exclude posterior urethral valves in any boy with symptoms pertaining to the urinary tract. A MCU should invariably be included in the radiological work-up.


A new species of Prosopocoilus Hope amp; Westwood, 1845 from China and Vietnam (Coleoptera: Lucanidae: Lucaninae).
A new species of stag beetle, Prosopocoilus zhuchuangi new species (Coleoptera: Lucanidae: Lucaninae) is described from China (Guizhou) and Vietnam. It is closely related to P. fulgens (Didier, 1927), sharing a fringe of dense setae in the apical 2/3 of the mesal sides of the mesotibiae and metatibiae. Diagnostic characters of the two species are illustrated and compared.


Synthesis, Characterisation and Antifungal Activities of Some New Copper(II) Complexes of Isomeric 3,5,7,7,10,12,14,14-Octamethyl-1,4,8,11-Tetraazacyclotetradecanes.
Three isomeric Me(8)[14]anes, L(A), L(B) and L(C), undergo complexation with copper(II) salts to form a series of [CuLX(n)(H(2)O)(x)]X(y).(H(2)O)(z) complexes where L = L(A), L(B) and L(C); X = Cl, Br, NO(3); n, x, y and z may have values of 0, 1 or 2. The complexes have been characterised on the basis of analytical, spectroscopic, magnetic and conductance data. Further, the X-ray crystal structure of one complex, [CuL(B)(OH(2))(2)](NO(3))(2), has been determined. The antifungal activity of all three isomeric ligands and their complexes has been investigated against a range of phytopathogenic fungi.


Rapid onset of rhabdomyolysis after switching to a raltegravir-based antiretroviral regimen.
Raltegravir is the first integrase inhibitor antiretroviral agent that has been demonstrated to have antiviral efficacy and safety. However, the US Food and Drug Administration has recommended use with caution in patients with risk factors for rhabdomyolysis, based on four case reports of rhabdomyolysis in patients with identifiable risk factors. We present a 32-year-old Asian man with human immunodeficiency virus (HIV), but without other underlying diseases, who developed rapid-onset, raltegravir-associated rhabdomyolysis and hyperlactatemia. Our patient lacked predisposing factors for rhabdomyolysis, and the rapid onset time of 4 days was the shortest reported. Therefore, clinicians should exercise caution when using raltegravir and closely monitor all patients for the symptoms of muscle pain and weakness. This case has been reported to the National Adverse Drug Reactions Reporting System of the Department of Health in Taiwan.


Effects of peer-led debriefing using simulation with case-based learning: Written vs. observed debriefing.
Peer-led written debriefing (PLWD) and peer-led observed debriefing (PLOD) are types of peer-led debriefing. Despite their advantages, these methods are sparingly used among debriefing experts. To identify effects of peer-led debriefing (written versus observed) using simulation with case-based learning (CBL) and compare levels of satisfaction with CBL, debriefing, and simulation-based learning (SBL) between the two groups. Quasi-experimental study used a pretest-posttest non-equivalent control group. Department of Nursing in C province, South Korea. Sixty-nine third-year undergraduate nursing students (PLWD, n = 33; PLOD, n = 36). Differences in clinical performance competency, and satisfaction of CBL, SBL, and debriefing between the PLWD and PLOD groups were determined. Clinical performance competency scores of posttest in both the PLWD and PLOD groups were significantly higher than those of pretest. There were no significant differences in any item except for item of 'communication' (t = -2.150, p = .047) between the PLWD and PLOD groups. There were no significant differences in satisfaction with CBL (t = -0.874, p = .385), simulation (t = -0.701, p = .485), or debriefing (t = -1.024, p = .309) between the two groups. This study suggests that both the PLWD and PLOD could be used to achieve students' learning outcomes when debriefing experts are unavailable.


Mechanical analysis of Kirschner wire fixation in a phalangeal model.
Transverse divisions of the mid-shaft of freshly frozen pig metacarpals were fixed with Kirschner wires of two sizes and using four different configurations. Compared to the usual cross-pin fixation using wires of 0.889 mm. four wires (0.712 mm) eccentrically placed and with their ends hooked provided a 300% improvement in bending rigidity and 170% in bending movement.


Effects of adenosine 3' : 5'-monophosphate and guanosine 3' : 5'-monophosphate on calcium uptake and phosphorylation in membrane fractions of vascular smooth muscle.
The effects of adenosine 3' : 5'-monophosphate (cyclic AMP), guanosine 3' : 5'-monophosphate (cyclic GMP) and exogenous protein kinase on Ca uptake and membrane phosphorylation were studied in subcellular fractions of vascular smooth muscle from rabbit aorta. Two functionally distinct fractions were separated on a continuous sucrose gradient: a light fraction enriched in endoplasmic reticulum (fraction E) and a heavier fraction containing mainly plasma membranes (fraction P). While cyclic AMP and cyclic GMP had no effect on Ca uptake in the absence of oxalate, both cyclic nucleotides inhibited the rate of oxalate-activated Ca uptake when used at concentrations higher than 10(-5) M. The addition of bovine heart protein kinase to either fraction produced an increase in the rate of oxalate-activated Ca uptake which was further augmented by cyclic AMP. Cyclic GMP caused smaller stimulations of protein kinase-catalyzed Ca uptake than cyclic AMP. Mg-dependent phosphorylation, attributable to endogenous protein kinase(s), was inhibited in fraction E by low concentrations (10(-8) M) of both cyclic AMP and cyclic GMP. In fraction P, an inhibition by cyclic AMP occurred also at a concentration of 10(-8) M, while with cyclic AMP a concentration of 10(-5) M was required for a similar inhibition. Bovine heart protein kinase stimulated the phosphorylation of the membrane fractions much more than Ca uptake. In fraction E, in the presence of bovine protein kinase, both cyclic AMP and cyclic GMP stimulated phosphorylation up to 200%. Under these conditions, no stimulation was observed in fraction P. These results are compatible with the hypothesis that in vascular smooth muscle soluble rather than particulate protein kinases are involved in the regulation of intracellular Ca concentration.


The diagnosis of upper urinary tract obstruction in children: comparison of diuresis renography and pressure flow studies.
We report the use of diuresis renography and pressure flow studies to diagnose urinary tract obstruction in 41 collecting systems of 33 children. If differential pressures between the renal pelvis and the bladder in excess of 22 cm. water at a flow rate of 10 ml. per minute is accepted as evidence of obstruction and below 15 cm. water is accepted as normal the interpretation of the renogram showing O'Reilly's pattern IIIa as evidence of stasis without obstruction was correct in 74 per cent of the cases. Likewise, the interpretation of O'Reilly's renogram pattern IIIb as showing partial obstruction was correct in only 40 per cent of the cases. Thus, we urge caution in the use of the diuresis renogram to diagnose or to rule out upper urinary tract obstruction.


Use of Gelidium amansii as a promising resource for bioethanol: a practical approach for continuous dilute-acid hydrolysis and fermentation.
A facile continuous method for dilute-acid hydrolysis of the representative red seaweed species, Gelidium amansii was developed and its hydrolysate was subsequently evaluated for fermentability. In the hydrolysis step, the hydrolysates obtained from a batch reactor and a continuous reactor were systematically compared based on fermentable sugar yield and inhibitor formation. There are many advantages to the continuous hydrolysis process. For example, the low melting point of the agar component in G. amansii facilitates improved raw material fluidity in the continuous reactor. In addition, the hydrolysate obtained from the continuous process delivered a high sugar and low inhibitor concentration, thereby leading to both high yield and high final ethanol titer in the fermentation process.


An integrated suite of modeling tools that empower scientists in structure- and property-based drug design.
Structure- and property-based drug design is an integral part of modern drug discovery, enabling the design of compounds aimed at improving potency and selectivity. However, building molecules using desktop modeling tools can easily lead to poor designs that appear to form many favorable interactions with the protein's active site. Although a proposed molecule looks good on screen and appears to fit into the protein site X-ray crystal structure or pharmacophore model, doing so might require a high-energy small molecule conformation, which would likely be inactive. To help scientists make better design decisions, we have built integrated, easy-to-use, interactive software tools to perform docking experiments, de novo design, shape and pharmacophore based database searches, small molecule conformational analysis and molecular property calculations. Using a combination of these tools helps scientists in assessing the likelihood that a designed molecule will be active and have desirable drug metabolism and pharmacokinetic properties. Small molecule discovery success requires project teams to rapidly design and synthesize potent molecules with good ADME properties. Empowering scientists to evaluate ideas quickly and make better design decisions with easy-to-access and easy-to-understand software on their desktop is now a key part of our discovery process.


Combination of polysaccharides from Astragalus membranaceus and Codonopsis pilosula ameliorated mice colitis and underlying mechanisms.
Astragalus membranaceus and Codonopsis pilosula which are two Chinese medicinal herbs are often combinedly used as monarch drugs in Traditional Chinese Medicine (TCM) prescriptions to treat ulcerative colitis (UC). However, the exact mechanisms and effective constituents of the two herbs remain unclear. Polysaccharides are the main active ingredients of the two medicinal herbs and some specific polysaccharides extracted from the two medicinal herbs have been proven effective in relieving colitis. Hence, we speculated that polysaccharides of the two medicinal herbs may be the material basis for compatibility in TCM prescriptions to treat UC. In the research, total polysaccharides of A. membranaceus and C. pilosula extractum, named AERP and CERP respectively, were administrated to 2.5% dextran sulfate sodium (DSS)-induced acute colitis mice by dosing alone and in combination to test this hypothesis. 5-aminosalicylic acid (5-ASA, 100 mg/kg/d) was selected as the positive drug. The basic indexes of colitis mice including body weight, stool bleeding, stool consistency and colon lengths were recorded. In addition, tissue inflammatory factors, mucosa-associated proteins, fecal short chain fatty acids (SCFAs) and gut microbiota were also analyzed. The co-administration of AERP and CERP at specific doses could improve the clinical symptoms, reestablish the immune balance, and alleviate colonic mucosal injury in colitis mice. The unique efficacy of co-administration relied on activation of the aryl hydrocarbon receptor (AhR) and up-regulation of isovaleric acid and butyrate. In addition, the structure of intestinal flora was recovered in the co-administration group. Our research proved the efficacy after co-administration of total polysaccharides from A. membranaceus and C. pilosula on colitis mice which provided a theoretical basis for their compatibility in TCM prescriptions to treat UC.


Human dentin materials for minimally invasive bone regeneration: Animal studies and clinical cases.
Bone, platelet concentrate, and tooth-derived dentin/cementum have been used as autologous materials in regenerative medicine Dentin materials were first recycled in 2002 for bone regeneration in humans, although bone autografts were noted in the 19th century, and auto-platelet concentrates were developed in 1998. Dentin/cementum-based material therapy has been applied as an innovative technique for minimally invasive bone surgery, while bone autografts are associated with donor site morbidity. In October 2021, PubMed, Google Scholar, Scopus, and the Cochrane Library databases from 1980 to 2020 were screened. The demineralized dentin/cementum matrix (DDM) had better performance in bone induction and bone regeneration than mineralized dentin. Unlike cell culture therapy, DDM is a matrix-based therapy that includes growth factors. A matrix-based system is a realistic and acceptable treatment, even in developing countries. The aim of this review was to summarize the evidence related to both animal studies and human clinical cases using human dentin materials with a patch of cementum, especially DDM.


Generalism and the evolution of parasite virulence.
The evolution of parasite-imposed host harm (virulence) will be affected by numerous factors, not least the range of hosts that parasites can infect. Here, we consider four ways that parasite host range (generalism) might directly affect observed levels of parasite virulence: costs of generalism, multiplicity of infection, maladaptive virulence, and host availability. Integrating parasite infectivity range with life-history evolution will generate novel general hypotheses for the evolutionary ecology of virulence, as well as explicit predictions about the virulence of emerging diseases resulting from host shifts.


Retracted: Deep Learning and Improved HMM Training Algorithm and Its Analysis in Facial Expression Recognition of Sports Athletes.
[This retracts the article DOI: 10.1155/2022/1027735.].


Role of disulfide bonds in folding and secretion of human lysozyme in Saccharomyces cerevisiae.
We examined folding and secretion of human lysozyme using four mutants each lacking two cysteines expressed in a yeast secretion system. Our results have revealed that the formation of the disulfide bond Cys6/Cys128 in human lysozyme is a prerequisite for correct folding in vivo in yeast. Substitution of Ala for Cys77 and Cys95 gave eight-fold greater secretion of a molecule with almost the same specific activity as that of the native enzyme. Substitutions of the other cysteines gave molecules that were secreted at a lower rate and had lower specific activities than the native enzyme. These are the first findings that the individual disulfide bonds of human lysozyme have different functions in folding and secretion in vivo.


Anabolic-androgenic steroid abuse and psychopathology.
Anabolic steroid abuse is a significant public health problem. There is evidence from both case reports and empirical studies that abuse of these drugs causes significant psychiatric and medical effects. There appears to be a relationship between increased dosages and severity of psychiatric symptomatology. Research is needed on the role of pathologic personality traits in the initiation and maintenance of anabolic steroid abuse.


Snap-to-it probes: chelate-constrained nucleobase oligomers with enhanced binding specificity.
We describe snap-to-it probes, a novel probe technology to enhance the hybridization specificity of natural and unnatural nucleic acid oligomers using a simple and readily introduced structural motif. Snap-to-it probes were prepared from peptide nucleic acid (PNA) oligomers by modifying each terminus with a coordinating ligand. The two coordinating ligands constrain the probe into a macrocyclic configuration through formation of an intramolecular chelate with a divalent transition metal ion. On hybridization with a DNA target, the intramolecular chelate in the snap-to-it probe dissociates, resulting in the probe 'snapping-to' and binding the target nucleic acid. Thermal transition analysis of snap-to-it probes with complementary and single-mismatch DNA targets revealed that the transition between free and target-bound probe conformations was a reversible equilibrium, and the intramolecular chelate provided a thermodynamic barrier to target binding that resulted in a significant increase in mismatch discrimination. A 4-6 degrees C increase in specificity (DeltaT(m)) was observed from snap-to-it probes bearing either terminal iminodiacetic acid ligands coordinated with Ni(2+), or terminal dihistidine and nitrilotriacetic acid ligands coordinated with Cu(2+). The difference in specificity of the PNA oligomer relative to DNA was more than doubled in snap-to-it probes. Snap-to-it probes labeled with a fluorophore-quencher pair exhibited target-dependent fluorescence enhancement upon binding with target DNA.


Molecular characterization of novel bipartite begomovirus associated with enation leaf disease of Garden croton (Codiaeum variegatum L.).
Garden croton (Codiaeum variegatum L.) plants showing typical begomovirus symptoms of vein twisting, enation and curling were collected from different gardens at Varanasi, Uttar Pradesh state of India ranged from 20 to 30%. All the 10 ten (CR1-CR10) infected samples of garden croton resulted in expected amplicon of 1.2 Kb in PCR specific to begomoviruses. No amplification was obtained for betasatellite and alphasatellite specific primers. The complete genome sequence of DNA-A and DNA-B for two isolates (CR1 and CR2) was obtained through rolling cycle amplification (RCA) and comparisons were made with other begomoviruses using Sequence Demarcation Tool (SDT) which revealed that, DNA-A of two isolates, CR1 (Acc.No.: MW816855) and CR2 (Acc.No.: MW816856) showed maximum nucleotide (nt) identity of 85.7-85.9% with Tomato leaf curl Karnataka virus, which is below the threshold percentage of begomovirus species demarcation, hence considered as novel begomovirus and proposed the name Garden croton enation leaf curl virus (CroELCuV) [IN: Varanasi: Croton: 18]. Further, DNA-B these isolates shared maximum nt identity of 91.0-92.2% (DNA-B) with Tomato leaf curl New Delhi virus. Recombination and GC plot analysis showed that the recombination occured at in low GC content regions of DNA-A and DNA-B of the CroELCuV and are derived from the previously reported several begomoviruses. This is the first record of novel bipartite begomovirus associated with vein twisting, enation and leaf curling of disease of garden garden croton in India and world. The online version contains supplementary material available at 10.1007/s13337-022-00772-0.


Attention and schema violations of real world scenes differentially modulate time perception.
In the real world, object arrangement follows a number of rules. Some of the rules pertain to the spatial relations between objects and scenes (i.e., syntactic rules) and others about the contextual relations (i.e., semantic rules). Research has shown that violation of semantic rules influences interval timing with the duration of scenes containing such violations to be overestimated as compared to scenes with no violations. However, no study has yet investigated whether both semantic and syntactic violations can affect timing in the same way. Furthermore, it is unclear whether the effect of scene violations on timing is due to attentional or other cognitive accounts. Using an oddball paradigm and real-world scenes with or without semantic and syntactic violations, we conducted two experiments on whether time dilation will be obtained in the presence of any type of scene violation and the role of attention in any such effect. Our results from Experiment 1 showed that time dilation indeed occurred in the presence of syntactic violations, while time compression was observed for semantic violations. In Experiment 2, we further investigated whether these estimations were driven by attentional accounts, by utilizing a contrast manipulation of the target objects. The results showed that an increased contrast led to duration overestimation for both semantic and syntactic oddballs. Together, our results indicate that scene violations differentially affect timing due to violation processing differences and, moreover, their effect on timing seems to be sensitive to attentional manipulations such as target contrast.


Ultra-performance chromatography-electrospray tandem mass spectrometry analysis of bile acid profiles in the enterohepatic circulation following geniposide and acetaminophen-induced liver injury.
Bile acids (BAs) play an important role in pre-diagnosing drug-induced liver injury (DILI). However, in clinical practice, different types of liver injury are characterized by different pathogeneses and pathological manifestations. Therefore, whether BAs can be used as biomarkers across different DILIs remains unclear. In this study, an ultra-performance chromatography-mass spectrometry (MS)/MS-based technique was developed for the simultaneous quantitative analysis of 31 BAs in the serum, liver, feces, urine, and intestinal contents of rats treated with acetaminophen (APAP) and geniposide to induce liver injury. The total extraction recovery for representative analytes ranged between 80.60% and 99.23% in the serum, urine, liver, feces, and intestinal contents. The correlation coefficients for all standard curves of the different matrices were at least 0.99. Validation of the BA analytical method including selectivity, residue, lower limit of quantification, accuracy, precision, matrix effect, and stability conformed with the biospecimen quality control standards of the Chinese Pharmacopoeia (version 2020). Serum biochemical and pathohistological analyses revealed APAP- and geniposide-induced hepatocellular and cholestatic DILI, respectively, with different effects on BA profiles in the enterohepatic circulation. Metabolomics further revealed that the trends in BA changes in the serum, feces, urine, and intestinal tissues were consistent between the geniposide- and APAP-treated groups. However, in the liver, the total BAs (TBA) concentration increased by 1.70 fold in the geniposide group but decreased by 43% in the APAP group compared with the control group. Multivariate analysis revealed differentially expressed BAs, including TCA, CA, and GCA, which are potential biomarkers for DILI, in the serum, liver, and urine following treatment with geniposide. Interestingly, the differentially expressed BAs in the APAP group were similar to those in the control group. Additionally, the magnitude of changes in the TBA in the urine (3.3 fold and 15.5 fold in the APAP and geniposide groups, respectively) was higher than that in the blood (290 fold and 640 fold in the APAP and geniposide groups, respectively). However, given the BA profiles after geniposide- and APAP-induced liver injury, BAs were found to be more suitable as biomarkers for diagnosing cholestatic liver injury. Overall, the BA assay developed in this study is rapid, simple, accurate, validated, sensitive, and suitable for analyzing the levels and distribution of BAs in various parts of the enterohepatic circulation.


Double Asymmetric Induction During the Addition of (RP)-Menthyl Phenyl Phosphine Oxide to Chiral Aldimines.
P,C-Stereogenic α-amino phosphine oxides were prepared from the addition of (RP )-menthyl phenyl phosphine oxide to chiral aldimines under neat condition at 80 °C in up to 91:9 drC and 99% yields. The diastereoselectivity was mainly induced by chiral phosphorus that showed matched or mismatched induction with (S)- or (R)-aldimines, respectively.


Non-linear modeling of 1H NMR metabonomic data using kernel-based orthogonal projections to latent structures optimized by simulated annealing.
Linear multivariate projection methods are frequently applied for predictive modeling of spectroscopic data in metabonomic studies. The OPLS method is a commonly used computational procedure for characterizing spectral metabonomic data, largely due to its favorable model interpretation properties providing separate descriptions of predictive variation and response-orthogonal structured noise. However, when the relationship between descriptor variables and the response is non-linear, conventional linear models will perform sub-optimally. In this study we have evaluated to what extent a non-linear model, kernel-based orthogonal projections to latent structures (K-OPLS), can provide enhanced predictive performance compared to the linear OPLS model. Just like its linear counterpart, K-OPLS provides separate model components for predictive variation and response-orthogonal structured noise. The improved model interpretation by this separate modeling is a property unique to K-OPLS in comparison to other kernel-based models. Simulated annealing (SA) was used for effective and automated optimization of the kernel-function parameter in K-OPLS (SA-K-OPLS). Our results reveal that the non-linear K-OPLS model provides improved prediction performance in three separate metabonomic data sets compared to the linear OPLS model. We also demonstrate how response-orthogonal K-OPLS components provide valuable biological interpretation of model and data. The metabonomic data sets were acquired using proton Nuclear Magnetic Resonance (NMR) spectroscopy, and include a study of the liver toxin galactosamine, a study of the nephrotoxin mercuric chloride and a study of Trypanosoma brucei brucei infection. Automated and user-friendly procedures for the kernel-optimization have been incorporated into version 1.1.1 of the freely available K-OPLS software package for both R and Matlab to enable easy application of K-OPLS for non-linear prediction modeling.


Gender differences among persons entering medication treatment for opioid use disorder in the community.
We evaluated gender differences among persons initiating medications for opioid use disorder (MOUD). Analyses of baseline assessments for a study evaluating the impact of MOUD on outcomes included: demographics, DSM-5 diagnoses, depression severity, quality of life (QoL), and medication history (N = 125). When compared to men, women had a greater prevalence of generalized anxiety and posttraumatic stress disorders; and worse psychological QoL. Women were less likely to be prescribed psychiatric medications. Women may benefit from tailored multidisciplinary programs with MOUD. This study identified that women with OUD seeking MOUD in the community had greater sedative hypnotic nonprescribed medication use and psychiatric comorbidity than men, all of which can contribute to poorer retention on MOUD and higher risk of morbidity and mortality. Thus, concurrent psychiatric disorder screening and treatment integrated with MOUD may improve retention on MOUD, opioid relapse and overdose for women.


Preparation, characterization and application of haemoglobin nanoparticles for detection of acrylamide in processed foods.
The nanoparticles of haemoglobin (HbNPs) were prepared by desolvation method and characterized by transmission electron microscopy (TEM),UV-vis spectroscopy, Fourier transformation infra red (FTIR) spectroscopy and X-ray diffraction (XRD) and atomic force microscopy (AFM). Protein profile of HbNPs was also studied by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). An amperometric acrylamide biosensor was constructed by immobilizing covalently HbNPs onto polycrystalline Au electrode. The Au electrode was characterized by scanning electron microscopy (SEM) and electrochemical impedance spectra (EIS) before and after immobilization of HbNPs. The biosensor showed optimum current response within 2s at 0.26V, pH 5.0 at room temperature (20°C). The biosensor measured the acrylamide concentration in processed foods. The working range of biosensor was 0.1nm-100mM with a limit of detection (LOD) as low as 0.1nM. The biosensor measured acrylamide concentration in various processed foods such as biscuits, bread, potato crisps, "kurkure", nuts and fried cereals. The analytical recovery of added acrylamide in aqueous extract of food at 5 and 10mM was 99% and 98% respectively. Within-and between-batch, co-efficient of variations were 3.85% and 4.67% respectively. The structural analogs of acrylamide such as acrylic acid and propionic acid had practically no interference on the biosensor.


Ectopic over-expression of HaFT-1, a 14-3-3 protein from Haloxylon ammodendron, enhances acquired thermotolerance in transgenic Arabidopsis.
Haloxylon ammodendron, an important shrub utilized for afforestation in desert areas, can withstand harsh ecological conditions such as drought, high salt and extreme heat. A better understanding of the stress adaptation mechanisms of H. ammodendron is vital for ecological improvement in desert areas. In this study, the role of the H. ammodendron 14-3-3 protein HaFT-1 in thermotolerance was investigated. qRT-PCR analysis showed that heat stress (HS) priming (the first HS) enhanced the expression of HaFT-1 during the second HS and subsequent recovery phase. The subcellular localization of YFP-HaFT-1 fusion protein was mainly detected in cytoplasm. HaFT-1 overexpression increased the germination rate of transgenic Arabidopsis seeds, and the survival rate of HaFT-1 overexpression seedlings was higher than that of wild-type (WT) Arabidopsis after priming-and-triggering and non-primed control treatments. Cell death staining showed that HaFT-1 overexpression lines exhibited significantly reduced cell death during HS compared to WT. Transcriptome analysis showed that genes associated with energy generation, protein metabolism, proline metabolism, autophagy, chlorophyll metabolism and reactive oxygen species (ROS) scavenging were important to the thermotolerance of HS-primed HaFT-1 transgenic plants. Growth physiology analysis indicated that priming-and-triggering treatment of Arabidopsis seedlings overexpressing HaFT-1 increased proline content and strengthened ROS scavenging activity. These results demonstrated that overexpression of HaFT-1 increased not only HS priming but also tolerance to the second HS of transgenic Arabidopsis, suggesting that HaFT-1 is a positive regulator in acquired thermotolerance.


Surface excess isotherms of organic solvent mixtures in a system made of liquid carbon dioxide and a silicagel surface.
The surface excess isotherms of methanol, ethanol, 2-propanol and acetonitrile from liquid carbon dioxide on a silica adsorbent were measured, using the minor disturbance method. The minor disturbance peaks - or system peaks - of each organic modifier were recorded using UV-detection in the whole composition range of the organic/liquid carbon dioxide mixtures, the whole composition range was completed by injecting the modifiers into pure liquid carbon dioxide as well. The excess isotherms were calculated based on the retention of the organic solvent signals. Our results show an enrichment of the organic modifier at the adsorbent surface. The alcohols show multilayer adsorption with an extremely high retention on the silica surface while acetonitrile shows weaker interactions and only a slight trend toward the formation of a multilayer above the surface.


Subjective well-being in schizophrenia: a randomised controlled open-label 12-month non-inferiority study comparing quetiapine XR with risperidone (RECOVER).
This randomised 12-month open study analysed the effectiveness of quetiapine XR (400-800 mg) versus risperidone (2-6 mg) on subjective well-being in schizophrenia (NCT00600756). Primary objective was to demonstrate non-inferiority of quetiapine XR to risperidone in 6-month responder rate using the Subjective Well-Being under Neuroleptics scale (SWN-K) (per-protocol at Month 6 [PP 6] population). Non-inferiority was defined as the lower limit of the 95% confidence interval (CI) greater than -9.7% for the adjusted difference between quetiapine XR and risperidone. Secondary objectives included non-inferiority of quetiapine XR versus risperidone (lower limit of 95% CI greater than -7.5 points) for SWN-K change from baseline to Month 12 (PP 12). 798 patients were randomised (quetiapine XR, n=395; risperidone, n=403); at Month 12, 212 (54%) and 227 (56%) patients, respectively, completed the study. At Month 6, SWN-K responder rate in the PP 6 population was 65% (136/210) with quetiapine XR and 68% (158/232) with risperidone (adjusted treatment difference: -5.7%; 95% CI: -15.1, 3.7); thus, non-inferiority could not be established. SWN-K change from baseline to Month 12 was 23.2 points for quetiapine XR and 21.1 points for the risperidone group; treatment difference was 2.1 (95% CI: -0.8; 5.0); non-inferiority was established (PP 12). SWN-K response at 6 months was comparable between the two antipsychotics. However, with a lower than expected responder rate and a lower than expected number of evaluable patients in the PP 6 population, non-inferiority was not demonstrated. A secondary objective (SWN-K total score) established non-inferiority of quetiapine XR to risperidone at Month 12.


The catalytic domain of the neurofibromatosis type 1 gene product stimulates ras GTPase and complements ira mutants of S. cerevisiae.
Sequencing of the neurofibromatosis gene (NF1) revealed a striking similarity among NF1, yeast IRA proteins, and mammalian GAP (GTPase-activating protein). Using both genetic and biochemical assays, we demonstrate that this homology domain of the NF1 protein interacts with ras proteins. First, expression of this NF1 domain suppressed the heat shock-sensitive phenotype of yeast ira1 and ira2 mutants. Second, this NF1 domain, after purification as a glutathione S-transferase (GST) fusion protein, strongly stimulated the GTPase activity of yeast RAS2 and human H-ras proteins. The GST-NF1 protein, however, did not stimulate the GTPase activity of oncogenic mutant ras proteins, H-rasVal-12 and yeast RAS2Val-19 mutants, or a yeast RAS2 effector mutant. These results establish that this NF1 domain has ras GAP activity similar to that found with IRA2 protein and mammalian GAP, and therefore may also regulate ras function in vivo.


The relationship between trunk muscle electromyography and lifting moments in the sagittal and frontal planes.
In this study, we explore the relationship between moments in the frontal and sagittal planes, generated by a lifting task, vs the electromyographic (EMG) activity of right and left trunk muscle groups. In particular, we postulate that the functional dependence between erector spinae muscle activity and the applied lifting moments about the spine is as follows: the sum of left and right erector spinae processed EMG depends on the sagittal plane moment, and the difference of left and right erector spinae processed EMG depends on the frontal plane moment. A simple out-of-sagittal plane physical model, treating the lumbar spine as a two degree-of-freedom pivot point is discussed to justify these hypotheses. To validate this model, we collected surface EMG and lifting moment data for ten males performing a grid of frontal and sagittal plane lifting tasks. A digital RMS-to-DC algorithm was developed for processing raw EMG. For these tests, we measured EMG for the left and right erector spinae and for the left and right external oblique muscles. The processed EMG signals of the left and right erector spinae muscles are summed and differenced for comparison to the measured sagittal and frontal plane moments. A linear correlation (r2) of 0.96 was obtained for the sum of erector spinae EMG vs the sagittal plane moment; a corresponding value of r2 = 0.95 was obtained for the difference vs the frontal plane moment. No correlations (r2 less than 0.004) was found for the sagittal plane moment and the difference of the left and right erector spinae EMG, and the frontal plane moment and the sum of the left and right erector spinae EMG.