Volumetric analysis of MRONJ lesions by semiautomatic segmentation of CBCT images.
The purpose of this study was to evaluate potential differences in volumes of areas of osteolysis caused by medication-related osteonecrosis of the jaw (MRONJ) between the upper and lower jaw. We aim to analyze the clinical relevance of volumetric measurement of osteolytic lesions for surgical planning of MRONJ patients. Sixty-seven patients who were clinically and histopathologically diagnosed with MRONJ were retrospectively included in this study. Cone beam computed tomography (CBCT) images were evaluated according to localization, affected anatomical structures, and volumetric measurement of osteolytic lesions caused by MRONJ in appliance of CBCT datasets by using ITK-SNAP. The most frequently affected localization is the mandible, whereas female patients show significantly more often lesions of the maxilla. The cortical bone was predominantly affected. Furthermore, the affection of teeth, sinus floor, inferior alveolar nerve canal, or even a pathological fracture of the mandible are infrequently existing. The volumetric measurements revealed a statistically significant greater absolute osteolysis volume in males. Image analysis and volumetric measurements of osteolytic lesions of MRONJ patients is a helpful tool to further understand the clinical appearance and identify compromised anatomic landmarks. Volumetric analysis aids in pre-surgical planning and visualizes the individual extent of the disease for each patient.


Maternal Depressive Symptoms and Infant Feeding Practices at Hospital Discharge: Findings from the Born in Queensland Study.
This study aims to explore association between maternal depressive symptoms and infant feeding practice at hospital discharge. Data were obtained from a birth cohort study based in Australia that linked to health administrative records. Maternal demographic data, mental health status derived from the Edinburgh Postnatal Depression Scale (EPDS), feeding practices of livebirths of at least 400 g or gestation periods of at least 20 weeks recorded during July-December 2015 were included (n = 14,658). Logistic regression models were performed to test association between presence of depressive symptoms and exclusive breast or formula feeding within 24 h prior to hospital discharge while adjusting for covariates known to be associated with breastfeeding. About 12% of women self-reported having depressive symptoms (EPDS score ≥ 10). Although only 7% of women (n = 1012) exclusively formula fed their babies, having depressive symptoms was associated with a 51% higher likelihood of exclusive formula feeding at hospital discharge. The association remains significant after adjustment for maternal age, gestational weeks, number of previous pregnancies, socioeconomic and partner status (p < 0.001) and all other covariates (p = 0.009). Having depressive symptoms was associated with increased likelihood of exclusive formula feeding. Routine measurement post-delivery and early management of maternal depressive symptoms may influence infant feeding practice and reduce prevalence of exclusive formula feeding at hospital discharge.


Referral patterns for infantile cataracts in two regions of the United States.
Delayed treatment of congenital or infantile cataracts can cause deprivation amblyopia. Prompt diagnosis and surgical intervention is critical for optimal outcomes. This study assessed referral patterns for congenital or infantile cataracts in two regions of the United States. The medical records of children 0-1 years of age with congenital or infantile cataracts at Stanford University (2008-2018) and Emory University (2010-2015) were reviewed retrospectively. A total of 111 children were included. Of these, 82 (74%) were initially evaluated by a primary care doctor, of whom 40 (49%) were referred directly to a pediatric cataract surgeon. Of 61 newborns 0-2 months of age, 9 (15%) were initially referred to an eye care provider before 6 weeks of age, but the initial evaluation by a pediatric cataract surgeon was delayed until after 6 weeks of age. Referral patterns were similar between the two institutions (P = 0.06). Many children with congenital of infantile cataracts are initially referred by a primary care doctor to an eye care provider who does not perform pediatric cataract surgery. Nevertheless, the majority of newborn infants with cataracts were evaluated by a pediatric cataract surgeon before 6 weeks of age.


Addressing Disparities Related to Access of Multimodality Breast Imaging Services Before and During the COVID-19 Pandemic.
Despite technological advancements focused on reducing breast cancer mortality through early detection, there have been reported disparities in the access to these imaging services with underserved patient populations (including racial minority groups and patients of low socioeconomic status) showing underutilization compared to other patient groups. These underserved populations tend to have more advanced breast cancer presentations, in part due to delays in diagnosis resulting in later stage of disease presentation. To make matters worse, the COVID-19 pandemic declared in March 2020 has resulted in significant healthcare disruptions leading to extensive delays in breast imaging services which are expected to negatively impact breast cancer mortality long-term. Given the worsening disparity in breast cancer mortality among racial/ethnic minorities and financially disadvantaged groups, it is vital to address these disparity gaps with the goal of reducing the barriers to timely breast cancer diagnosis and addressing breast cancer mortality differences among breast cancer patients. Therefore, this review aims to provide a discussion highlighting the disparities related to breast imaging access, the effects of the COVID-19 pandemic on these disparities, current targeted interventions implemented in breast imaging practices to reduce these disparities, and future directions on the journey to reducing disparity gaps for breast imaging patients. Tackling the root cause factors of the persistent breast cancer-related disparities is critical to meeting the needs of patients who are disadvantaged and can lead to continued improvement in the quality of individualized care for patients who have higher breast cancer morbidity and mortality risks.


Identification of hydrallazine and hydrallazine hydrazone metabolites in human body fluids and quantitative in vitro comparisons of their smooth muscle relaxant activity.
1 Serum and urine from hypertensive subjects on chronic oral hydrallazine therapy were studied using gas chromatographic/mass spectrometry techniques. 2 Metabolites resulting from acetylation, hydrolysis and conjugation reactions were detected. The acetone, pyruvate and alpha-ketoglutarate hydrazone were identified. 3 The activity of the pyruvate and alpha-ketoglutarate hydrazones were compared with that of hydrallazine using isolated rabbit aortic strips. 4 Both hydrazones were active under in vitro conditions, producing smooth muscle relaxant effects equal to those of hydrallazine. 5 It is concluded that hydrazone metabolites will contribute to the hypotensive effects of hydrallazine therapy in proportion to their relative abundance, persistence in vascular tissues and intrinsic activity.


Construction of N-7 methylguanine-related mRNA prognostic model in uterine corpus endometrial carcinoma based on multi-omics data and immune-related analysis.
N-7 methylguanine (m7G) is one of the most common RNA base modifications in post-transcriptional regulation, which participates in multiple processes such as transcription, mRNA splicing and translation during the mRNA life cycle. However, its expression and prognostic value in uterine corpus endometrial carcinoma (UCEC) have not been systematically studied. In this paper, the data such as gene expression profiles, clinical data of UCEC patients, somatic mutations and copy number variants (CNVs) are obtained from the cancer genome atlas (TCGA) and UCSC Xena. By analyzing the expression differences of m7G-related mRNA in UCEC and plotting the correlation network maps, a risk score model composed of four m7G-related mRNAs (NSUN2, NUDT3, LARP1 and NCBP3) is constructed using least absolute shrinkage and selection operator (LASSO), univariate and multivariate Cox regression in order to identify prognosis and immune response. The correlation of clinical prognosis is analyzed between the m7G-related mRNA and UCEC via Kaplan-Meier method, receiver operating characteristic (ROC) curve, principal component analysis (PCA), t-SNE, decision curve analysis (DCA) curve and nomogram etc. It is concluded that the high risk is significantly correlated with (P < 0.001) the poorer overall survival (OS) in patients with UCEC. It is one of the independent risk factors affecting the OS. Differentially expressed genes are identified by R software in the high and low risk groups. The functional analysis and pathway enrichment analysis have been performed. Single sample gene set enrichment analysis (ssGSEA), immune checkpoints, m6A-related genes, tumor mutation burden (TMB), stem cell correlation, tumor immune dysfunction and rejection (TIDE) scores and drug sensitivity are also used to study the risk model. In addition, we have obtained 3 genotypes based on consensus clustering, which are significantly related to (P < 0.001) the OS and progression-free survival (PFS). The deconvolution algorithm (CIBERSORT) is applied to calculate the proportion of 22 tumor infiltrating immune cells (TIC) in UCEC patients and the estimation algorithm (ESTIMATE) is applied to work out the number of immune and matrix components. In summary, m7G-related mRNA may become a potential biomarker for UCEC prognosis, which may promote UCEC occurrence and development by regulating cell cycles and immune cell infiltration. It is expected to become a potential therapeutic target of UECE.


Evaluation of postgraduate educational environment in a Nigerian teaching hospital.
Congenial educational environment (EE) is paramount to effective impartation of knowledge as required in residency training. In this study EE for residency training is evaluated using Postgraduate Hospital Educational Environment Measure (PHEEM). To assess the postgraduate educational environment at the University of Nigeria Teaching Hospital (UNTH), South-East Nigeria, using PHEEM and to determine if there are significant differences in PHEEM scores amongst various sub-groups of resident doctors. A cross-sectional study, employing a census survey, involving the administration of validated PHEEM questionnaires to residents in the Departments of Internal Medicine, Obstetrics/Gynaecology, Pediatrics and Surgery in the year 2018. Data entry and analysis were done using SPSS. ANOVA assessed significance of total scores and sub-scale scores. Cronbach's alpha was calculated. A total of 114 Males and 46 females; 93 registrars and 67 senior registrars responded giving 71% response rate. Overall PHEEM score was 85.82; Role autonomy (29.27), Perception of teaching (34.80), Perception of social support (21.55). Males scored more than females in total PHEEM score (p = 0.000, F = 148.235), perception of teaching (P = 0.000, F = 420), and perception of social support (p = 0.000, F = 162.95), but not in role autonomy (p = 0.748, F = 0.104). Registrars scored more than senior registrars in total PHEEM (p = 0.000, F = 67.159), role autonomy (p = 0.000, F = 25.123), Perception of teaching (p = 0.000, F = 18.042) but not in perception of social support (p = 0.31, F = 1.045). There were significant differences in total and subscale scores amongst the specialties. Cronbach's alpha was 0.915. Postgraduate educational environment in UNTH has more positives than negatives but with room for improvement. There are significant differences in PHEEM scores among various groups of resident doctors.


Perforation during gas reduction of intussusception.
Perforation during attempted gas-enema reduction of intussusception is more common than during a barium enema. In a review of 650 consecutive attempted gas enemas, perforation occurred in 7 infants (1.1%). Gross abdominal distension from the pneumoperitoneum may be rapid and cause splinting of the diaphragm, which leads to acute respiratory distress. This complication is readily recognised at the time of the gas enema, and may require immediate intervention by paracentesis using a 14-gauge needle. A review of 7 children with intussusception in whom perforation occurred revealed that all had radiologic evidence of bowel obstruction (air-fluid levels) prior to the enema, and the patients had had a relatively long history since the onset of symptoms. No perforation occurred during a delayed repeat enema reduction. Perforation during gas enema produces minimal peritoneal contamination. No pathological lesion at the lead point of the intussusception was identified in any of the children in whom perforation occurred.


Pancreatic beta cell neogenesis: Debates and updates.
Finding endogenous, renewable sources for insulin-producing beta cells in the adult pancreas is one of the holy grails of stem cell research and regenerative medicine. Through lineage tracing and scRNA-seq approaches, Gribben et al. (2021) have recently reported that Ngn3-expressing ductal cells could serve as progenitors for new beta cells in the adult pancreas.


Translational contributions of the experimental analysis of behavior.
It has been argued that to increase societal impact behavioral researchers must do more to address problems of obvious practical importance. The basic science wing of behavior analysis has been described as especially detached from this goal, but is it really necessary that basic science demonstrate social relevance? If so, why hasn't this occurred more often, and what can be done to improve the status quo? To address these questions and to stimulate discussion about the future of basic behavior science, I describe two widely embraced arguments in favor of pure basic science (that which is undertaken without concern for practical applications); explain why a translational research agenda is likely to better recruit tangible support for basic science; propose that addressing practical problems does not require basic science to abandon its focus on fundamental principles; and identify some possible impediments to translational innovation that may need to be addressed for basic behavior science to increase its translational footprint.


Oxidative cleavage of plasmid bluescript by water-soluble Mn-porphyrins and artificial oxidants or molecular oxygen.
A set of eight Mn(III)-porphyrins were used as catalysts in oxidative demolition of Plasmid Bluescript, to the nicked and linear forms, in the presence of different oxygen donors (NaOCl, H(2)O(2), AcOOH, t-BuOOH). The efficiency of the catalytic system is related to a combination of factors such as porphyrin structures, pH of the aqueous phase and nature of the primary oxidant. The highest catalytic activity was observed when ionic porphyrins were used as catalyst (the cationic being more active than the anionic) and NaOCl was used as primary oxidant at pH 9.5; in contrast, lipophilic catalysts proved to be completely unreactive towards the DNA, whichever oxidant used. The plasmid demolition was also achieved by irradiating the reaction mixture, containing Zinc porphyrins, with a white lamp; under these conditions, the highest efficiency was again observed with meso-tetra(1-methyl-4-pyridyl)porphyrin. However, preliminary experiments of photo activation applied on tumour cells (HCT 116) showed no dead cells with cationic porphyrin, while the amphiphilic Zn-tetra(4-hydroxyphenyl)porphyrin gave IC(50) values at 5 x 10(-2) microM concentration (37.1 ng/mL).


Vasculitic neuropathy.
Peripheral neuropathy is common in many vasculitic syndromes and may be the only manifestation of the underlying vasculitic disease. Although traditional teaching has been that a true multiple mononeuropathy is the classic clinical presentation of vasculitic neuropathy, an overlapping (or extensive) multiple mononeuropathy or a distal symmetric polyneuropathy is commonly encountered. Similarly, the leukocytoclastic reaction has traditionally been considered the primary mechanism of vessel injury in these diseases, although more recent evidence suggests that cellular-mediated mechanisms may be more important in peripheral nerve. In this review, new concepts concerning the clinical presentation, pathogenesis, diagnosis, and treatment of vasculitic neuropathy are discussed, particularly in relation to the syndrome of isolated peripheral nerve vasculitis.


[Portions of the ophthalmic nerve and its branches adjacent to the orbital roof and margin].
The nerves in the vicinity of the orbital roof, their length, anastomoses and the distribution at the supraorbital margin are described. Included is the length of the trigeminal nerves between the orbital margin and the entrance area of the trigeminal nerve in the pons.


MicroRNA-558 regulates the expression of cyclooxygenase-2 and IL-1β-induced catabolic effects in human articular chondrocytes.
Cyclooxygenase-2 (COX-2) is a major prostaglandin E2 (PGE2) synthetic enzyme and is involved in the pathogenesis of chronic inflammation and pain in osteoarthritis (OA). The objective of this study was to directly address whether microRNA (miR)-558 can control the interleukin (IL)-1β-mediated induction of COX-2 and catabolic effects in human articular chondrocytes. Total RNA was extracted from the cartilage tissues of normal and OA donors or cultured human articular chondrocytes. The expression of miR-558 was quantified by TaqMan assay. To investigate the repressive effect of miR-558 on COX-2 expression, human chondrocytes and chondrogenic SW1353 cells were transfected with mature miR-558 or an antisense inhibitor (anti-miR-558). The expression of COX-2 protein was determined by Western blot analysis and the involvement of miR-558 in IL-1β-induced catabolic effects was examined by Western blot analysis and enzyme-linked immunosorbent assay (ELISA). Direct interaction between miR-558 and the putative site in the 3'-untranslated region (UTR) of COX-2 messenger RNA (mRNA) was validated by luciferase reporter assay. Normal human articular cartilage expressed miR-558, and its expression was significantly lower in OA cartilage. Stimulation with IL-1β led to a significant reduction in miR-558 expression in normal and OA chondrocytes. IL-1β-induced activation of MAP kinase (MAPK) and nuclear factor-κB (NF-κB) decreased miR-558 expression and induced COX-2 expression in chondrocytes. The overexpression of miR-558 directly suppressed the luciferase activity of a reporter construct containing the 3'-UTR of human COX-2 mRNA and significantly inhibited IL-1β-induced upregulation of COX-2, while treatment with anti-miR-558 enhanced IL-1β-induced COX-2 expression and reporter activity in chondrocytes. Interestingly, IL-1β-induced activation of NF-κB and expression of matrix metalloproteinase (MMP)-1 and MMP-13 was significantly inhibited by miR-558 overexpression. These findings demonstrated that cartilage homeostasis is influenced by miR-558, which directly targets COX-2 and regulates IL-1β-stimulated catabolic effects in human chondrocytes.


T cell Ig and mucin domain-1-mediated T cell activation requires recruitment and activation of phosphoinositide 3-kinase.
Ligation of the transmembrane protein T cell Ig and mucin domain (Tim)-1 can costimulate T cell activation. Agonistic Abs to Tim-1 are also capable of inducing T cell activation without additional stimuli. However, little is known about the biochemical mechanisms underlying T cell stimulation or costimulation through Tim-1. We show that a tyrosine in Tim-1 becomes phosphorylated in a lck-dependent manner, whereupon it can directly recruit p85 adaptor subunits of PI3K. This results in PI3K activation, which is required for Tim-1 function. We also provide genetic evidence that p85 expression is required for optimal Tim-1 function. Thus, we describe a pathway from Tim-1 tyrosine phosphorylation to the PI3K signaling pathway, which appears to be a major effector of Tim-1-mediated T cell activation.


Harnessing Reversible Electronic Energy Transfer: From Molecular Dyads to Molecular Machines.
Reversible electronic energy transfer (REET) may be instilled in bi-/multichromophoric molecule-based systems, following photoexcitation, upon judicious structural integration of matched chromophores. This leads to a new set of photophysical properties for the ensemble, which can be fully characterized by steady-state and time-resolved spectroscopic methods. Herein, we take a comprehensive look at progress in the development of this type of supermolecule in the last five years, which has seen systems evolve from covalently tethered dyads to synthetic molecular machines, exemplified by two different pseudorotaxanes. Indeed, REET holds promise in the control of movement in molecular machines, their assembly/disassembly, as well as in charge separation.


Interdisciplinary case management: a model for intervention.
Interdisciplinary case management is required when clients present problems that do not fall within the purview of any one discipline. The interdisciplinary approach entails the participation of professional and support staff, along with the client and his/her family, in diagnosis, individual program planning, implementation, and evaluation. For example, interdisciplinary case management for a patient with Prader-Willi syndrome (PWS) results in cost-effective, efficacious treatment. Because of the diversity of symptoms, the treatment of Prader-Willi syndrome must incorporate knowledge and skills from a variety of areas. A model for the interdisciplinary case management of PWS is presented. The model is problem focused and emphasizes goals formulated and acted upon by the disciplines represented on the client's treatment team. Communication and coordination of efforts are central to the utility of the model. Additional benefits of interdisciplinary case management include the opportunity for ongoing education and role expansion of team members.


Gangliosides of the mouse spinal cord: a comparison in in vivo and in vitro tissues.
Ganglioside profiles in spinal cord from 13-day mouse fetuses, 21-day postnatal and adult mice were compared with those harvested from organotypic cross-sections of fetal mouse spinal cord grown for 28 days in vitro in a serum-free medium. All the major species of gangliosides reported for brain were present both in the in vivo tissue and cultured spinal cord, though not necessarily at each developmental stage examined. Fresh tissues showed increases and decreases in various gangliosides as have been reported for higher brain centers at similar stages of development in mammals and birds. However, qualitative and quantitative differences exist between fresh spinal cord and cultured cord explants as well as between galactose-grown and galactose-free cultures. Spinal cord explants grown in the presence of galactose showed measurable amounts of GM2 and GM3 which were not detected in the control-defined medium-grown cultures. The differences between the two culture groups may be related to interneuronal connectivity patterns.


The Hybrid II assay: a sensitive and specific real-time hybridization assay for the diagnosis of Theileria parva infection in Cape buffalo (Syncerus caffer) and cattle.
Corridor disease is an acute, fatal disease of cattle caused by buffalo-adapted Theileria parva. This is a nationally controlled disease in South Africa and strict control measures apply for the movement of buffalo, which includes mandatory testing for the presence of T. parva and other controlled diseases. Accurate diagnosis of the T. parva carrier state in buffalo using the official real-time hybridization PCR assay (Sibeko et al. 2008), has been shown to be affected by concurrent infection with T. sp. (buffalo)-like parasites. We describe the Hybrid II assay, a real-time hybridization PCR method, which compares well with the official hybridization assay in terms of specificity and sensitivity. It is, however, not influenced by mixed infections of T. sp. (buffalo)-like parasites and is as such a significant improvement on the current hybridization assay.


Advantageous comparison: using Twitter responses to understand similarities between cybercriminals ("Yahoo Boys") and politicians ("Yahoo men").
This article is about the manifestations of similarities between two seemingly distinct groups of Nigerians: cybercriminals and politicians. Which linguistic strategies do Twitter users use to express their opinions on cybercriminals and politicians? The study undertakes a qualitative analysis of 'engaged' tweets of an elite law enforcement agency in West Africa. We analyzed and coded over 100,000 'engaged' tweets based on a component of mechanisms of moral disengagement (i.e., advantageous comparison), a linguistic device. The results reveal how respondents defend the actions of online fraudsters ("the deviant group") by strategically comparing them to the wrongful acts of corrupt politicians ("the respectable group"). Similarly, the results show how respondents positioned this linguistic strategy to compare "the powerless group" (online fraudsters) and "the powerful group" (politicians) in society. Indeed, tweet responses suggest that the Economic and Financial Crimes Commission (EFCC) generally looks downwards for culprits (i.e., online fraudsters) while ignoring fraudulent politicians. We conclude that the process by which some actions are interpreted as a crime compared to others is a moral enterprise.


Erosion of penile prostheses: a complication of urethral catheterization.
We studied 9 patients with indwelling urethral catheters or who were using intermittent clean catheterization and who had received a penile prosthesis. A 56 per cent (5 of 9) incidence of urethral erosion was found in this population. Urethral erosion was a late complication, 80 per cent (4 of 5) of the time in our series, that usually presented several months after implantation of the prosthesis. We believe that the etiological factors that contributed to this disastrous complication were the friction and inflammation associated with catheterization. We currently construct a perineal urethrostomy in patients who desire a penile prosthesis and who perform intermittent catheterization. If intermittent catheterization is not feasible, insertion of a suprapubic tube is recommended. We additionally recommend insertion of an inflatable penile prosthesis, since this type is relatively soft most of the time and will not cause as much pressure at the end of the penis. Since instituting these procedures we have not encountered any erosion.


Genetic transformation of Triticeae cereals - Summary of almost three-decade's development.
Triticeae cereals are among the most important crop plants grown worldwide and being used for animal feed, food and beverages. Although breeding efforts evolved over the last ten thousand years our today's crop plants, biotechnological methods would help to speed up the process and incorporate traits impossible by conventional breeding. The main research topics were related to cover the future demand on our agricultural practices to supply sufficient food for a growing world population. Target traits are resistances against viral and fungal diseases, improvement of water and nitrogen use efficiency, to tackle plant architecture, both below and aboveground and to develop varieties that could grow on dry or salty locations. Other applications are considering accumulation of useful compounds or decreasing allergenicity. This review will summarize methods to generate the material including a section how genome engineering using gRNA/Cas (CRISPR/Cas) technology could further improve the methodology and will give an overview about recent and future applications.


Infantile ictal apneas in a child with williams-beuren syndrome.
Williams-Beuren syndrome is a genetic disorder rarely associated with seizures. The few described cases of Williams-Beuren syndrome and epilepsy have primarily involved infantile spasms and deletions extending beyond the common deletion region for this disorder. We present the case of a 5-week-old child with ictal apneas and typical Williams-Beuren syndrome deletion. Diagnosis was challenging, because the child had cardiac, respiratory, and gastrointestinal abnormalities typically associated with Williams-Beuren syndrome, which are also associated with cyanotic episodes. The results of interictal electroencephalography were normal, illustrating that prolonged electroencephalography is often essential in evaluation of suspected ictal apneas. Seizure freedom was achieved with carbamazepine. Sudden death is seen in Williams-Beuren syndrome, and this case raises the question whether some of these cases may be related to ictal apneas and could potentially be preventable with appropriate pharmaceutical intervention.


Comparison of the effects of remimazolam and dexmedetomidine on early postoperative cognitive function in elderly patients with gastric cancer.
To compare the effects of remimazolam and dexmedetomidine on early postoperative cognitive dysfunction (POCD) in aged gastric cancer patients. From June to December 2022, 104 elderly patients (aged 65-80 years) received laparoscopic radical resection of gastric cancer at the First Affiliated Hospital of Nanchang University. Using the random number table approach, the patients were separated into three groups: remimazolam (Group R), dexmedetomidine (Group D), and saline (Group C). The primary outcome was the incidence of POCD, and secondary outcomes included TNF-α and S-100β protein concentrations, hemodynamics, VAS scores, anesthesia recovery indicators, and the occurrence of adverse events within 48 h postoperatively. At 3 and 7 days after surgery, there were no statistically significant differences in the incidence of POCD, the MMSE and MoCA scores between groups R and D (p > 0.05). However, compared to the saline group, both groups had higher MMSE and MoCA scores and decreased incidences of POCD. These differences were statistically significant (p < 0.05). Between group R and group D, there were no statistically significant changes (p > 0.05) in the levels of TNF-α and S-100β protein at the three time points (at the end of the surgery, 1 day later, and 3 days later). Even though neither group's concentration of the two factors was as high as that of the saline group, the differences were statistically significant (p < 0.05). At all three time points-following induction (T2), 30 min into the operation (T3), and at the conclusion of the surgery (T4)-the heart rate and blood pressure in group R were greater than those in groups D and C. Statistics showed that the differences were significant (p < 0.05). The incidence of intraoperative hypotension was highest in group D and lowest in group R (p < 0.05). The dose of propofol and remifentanil, group C > group R > group D. Extubation and PACU residence times did not differ statistically significantly (p > 0.05) between the three groups. There was no significant difference in VAS scores between groups R and D after 24 h postoperatively (p > 0.05), although both had lower scores than group C, and the difference was statistically significant (p < 0.05). The VAS scores between the three groups at 72 h (T6) and 7 days (T7) were not statistically significant (p > 0.05). Adverse reactions such as respiratory depression, hypotension, bradycardia, agitation, drowsiness, and nausea and vomiting had the lowest incidence in group R and the highest incidence in group C (p < 0.05). Remimazolam is similarly beneficial as dexmedetomidine in lowering the incidence of early POCD in aged patients after radical gastric cancer resection, probably due to reduced inflammatory response.


Health care institutions in a regional network: a longitudinal case study of inter-organizing.
This is a second article reporting on the functioning of a regional federation in the Dutch health care field. It is a heterogeneous federation of health care delivery institutions (clinical, ambulatory, and primary care) within a geographical area of about 250,000 inhabitants. The first article on this subject, published in this journal in 1981, dealt with the facilities and obstacles during the founding process of the federation and with the problems concerning the making of a policy program (Soc. Sci. Med. 15A, 41-48, 1981). That was about five years after the inception of the federation and it seemed both possible and fruitful to carry out further evaluation of this particular case. A content analysis of all the 41 meetings of the federation could be performed on the agendas, minutes and other relevant documents. The results of this analysis, taken together with a substantial amount of information gathered by participant observation during these sessions, gave rise to certain conclusions and interpretations. They concerned the numbers and kinds of subjects discussed, the changes in their composition over the years, the varying amount of energy put into the development of the federation's organization, the evolution of the federation's task and its effectiveness in preparing regional plans for health care provision. The results of the analysis seemed to encourage this approach to regionalization. Developments during the most recent period, since 1982, will be described in a third article. Although in a legislative sense this year was important, the related enactment processes went on very slowly.(ABSTRACT TRUNCATED AT 250 WORDS)


High performance of combined HPV testing and genotyping for HPV16/18/52/58 in triaging women with minor cervical cytological abnormalities in northern Thailand.
Human papillomavirus (HPV) infection is an important cause of cervical cancer. Screening with cytology or combined cytology and HPV testing helps to detect early cervical cancers and precancerous lesions (high-grade squamous intraepithelial lesion or worse [HSIL+]). Minor cytological abnormalities (atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion) account for the majority of abnormal cervical cytology results, but only 10-20% of women with minor cytological abnormalities have histologic HSIL+. Triage tests are useful to identify the high-risk patients and reduce the colposcopy burden. This study was aimed to evaluate the triage performance of combined HPV DNA testing and genotyping. Cervical samples from women with minor cytological abnormalities, who underwent colposcopy at Chiang Mai University Hospital in northern Thailand between October 2010 and February 2014, were tested for HPV DNA using Hybrid Capture 2 (HC2). Genotyping was performed using Linear Array assay. Of 223 women with cervical histology confirmation, histologic HSIL+ was detected in 25 women (11.2%). The sensitivity, specificity, positive predictive value, and negative predictive value of 3 triage methods for histologic HSIL+ were; 100%, 47.5%, 19.4%, and 100% by HC2 only; 40.0%, 88.4%, 30.3%, and 92.1% by combined HC2 and genotypes HPV16/18; and 96.0%, 75.8%, 33.3%, and 99.3% by combined HC2 and genotypes HPV16/18/52/58. Triage using combined HC2 and genotypes HPV16/18/52/58 showed significantly greater area under the receiver operating curve than the other 2 methods (P < 0.001). Combined HPV DNA testing and genotyping for HPV16/18/52/58 is useful for triaging women with minor cervical cytological abnormalities in northern Thailand.


Comparison of the pathogenicity of two strains (wild type and vaccine-like) of porcine reproductive and respiratory syndrome virus (PRRSV) in experimentally infected sows.
The objective of this study was to compare two Korean strains of porcine reproductive and respiratory syndrome virus (PRRSV), namely a wild type (WT) strain and a vaccine-like (VL) strain, in respect of pathogenicity and viral distribution in the tissues. Both strains were of the North American genotype. Two groups of five pregnant sows were infected with either the WT or the VL strain 2 weeks before their expected farrowing date. The WT strain-inoculated sows showed abortion and premature farrowing, whereas the VL strain-inoculated sows remained clinically normal and did not farrow prematurely. Of the 18 liveborn piglets from the WT strain-inoculated sows, 14 had interstitial pneumonia. Of the 60 liveborn piglets from the VL strain-inoculated sows, only six had interstitial pneumonia. PRRSV antigen or nucleic acid was detected in 48/65 (73.8%) of stillborn and liveborn piglets from the WT strain-inoculated sows, but in only 12/64 (18.8%) of stillborn and liveborn piglets from the VL strain-inoculated sows.


Quantitative evaluation of experimental ischemic colitis correlated with the degree of artificial bowel obstruction in rats.
Experimental ischemic colitis proximal to artificial bowel obstruction was produced under poor regional circulatory conditions in rats. Only the vessels of the left hemi-colon were ligated to obtain poor circulation (ischemia). Two types of aluminum rings were used to obstruct the bowel at the most distal portion of the ischemic colon. One, with a 4 mm internal diameter, was used for the model of partial colon obstruction with ischemia (partial obstruction, n = 25) and the other, with a 2 mm internal diameter, was used for complete colon obstruction with ischemia (complete obstruction, n = 25). The circumference of the dilated bowel was larger in complete obstruction than in partial obstruction. Ischemic colitis developed in 9 of 25 rats (34.0%) with partial obstruction and 16 of 25 (64.0%) with complete obstruction. In terms of morphometry, over half of the ischemic lesions in complete obstruction were more than 1.0 cm2, but such a large size in partial obstruction was not observed. It was demonstrated that the depth of ischemic lesions gradually increased in extensive lesions. In conclusion, complete colon obstruction with ischemia frequently caused severer ischemic colitis, together with marked distention of the proximal bowel, than partial colon obstruction with ischemia.


Involvement of delta and mu opioid receptors in the acute and sensitized locomotor action of cocaine in mice.
Analogs of deltorphins, such as cyclo(Nδ, Nδ-carbonyl-d-Orn2, Orn4)deltorphin (DEL-6) and deltorphin II N-(ureidoethyl)amide (DK-4) are functional agonists predominantly for the delta opioid receptors (DOR) in the guinea-pig ileum and mouse vas deferens bioassays. The purpose of this study was to examine an influence of these peptides (5, 10 or 20 nmol, i.c.v.) on the acute cocaine-induced (10mg/kg, i.p.) locomotor activity and the expression of sensitization to cocaine locomotor effect. Sensitization to locomotor effect of cocaine was developed by five injections of cocaine at the dose of 10mg/kg, i.p. every 3 days. Our results indicated that DK-4 and DEL-6 differently affected the acute and sensitized cocaine locomotion. Co-administration of DEL-6 with cocaine enhanced acute cocaine locomotion only at the dose of 10 nmol, with minimal effects at the doses 5 and 20 nmol, whereas co-administration of DK-4 with cocaine enhanced acute cocaine-induced locomotion in a dose-dependent manner. Similarly to the acute effects, DEL-6 only at the dose of 10 nmol but DK-4 dose-dependently enhanced the expression of cocaine sensitization. Pre-treatment with DOR antagonist - naltrindole (5 nmol, i.c.v.) and mu opioid receptor (MOR) antagonist, β-funaltrexamine abolished the ability of both peptides to potentiate the effects of cocaine. Our study suggests that MOR and DOR are involved in the interactions between cocaine and both deltorphins analogs. A distinct dose-response effects of these peptides on cocaine locomotion probably arise from differential functional activation (targeting) of the DOR and MOR by both deltorphins analogs.


Clinicopathological features of the superficial spreading type of early gastric cancer.
BACKGROUND: During a 10-year period (1986-1995), 59 of 538 patients with early gastric cancer (11.0%) had the superficial spreading type of gastric cancer. We attempted to elucidate the clinicopathological features and investigated the influence of those features on surgical procedures and patient prognoses.METHODS: These 59 superficial spreading lesions were analyzed with respect to macroscopic type, lymph node (LN) metastasis, recurrent pattern, and method of surgical operation. In addition, the lesions were compared with those of 393 other patients with small-sized cancer.RESULTS: In both groups, the IIc type macroscopic lesion occurred most frequently, and the depressed subtype occurred more frequently than the elevated subtype. There was no significant histologic difference between the groups. The incidence of LN metastasis was 8.7% in early gastric cancer, 7.1% in small-sized cancer, and 20.3% in superficial spreading cancer. The incidence of lymphovascular invasion was 24.4% in small-sized cancer and 50.8% in superficial spreading cancer. The incidences of LN metastasis and lymphovascular invasion were greater in superficial spreading cancer than in small-sized cancer. Despite extensive preoperative examination, determination of the tumor margin was impossible in 26 of the 59 patients with superficial spreading cancer. The incidence of recurrence was 2.0% in small-sized cancer and 5.1% in superficial spreading cancer.CONCLUSIONS: A wide resection with extensive lymph node dissection (D2 or more) seems to be an appropriate treatment for the superficial spreading type of early gastric cancer.


Characterization of the proton binding sites of extracellular polymeric substances in an anaerobic membrane bioreactor.
This paper focuses on the characterization of the chemical compositions and acidic constants of the extracellular polymeric substances (EPSs) in an anaerobic membrane bioreactor treating synthetic brewery wastewater by using chemical analysis, linear programming analysis (LPA) of titration data, and FT-IR analysis. The linear programming analysis of titration data revealed that the EPSs have proton binding sites with pKa values from pKa ≤ 6, between 6 and 7, and approximately 9.8. The strong acidic sites (pKa ≤ 6) and some weak acidic sites (7.5 < pKa < 9.0) were found to be readily removed by 0.45-μm membrane filtration. In addition, the FT-IR analysis confirmed the presence of proteins, carbohydrates, nucleic acids, and lipids in the EPS samples. Based on the FT-IR analysis and the main chemical functional groups at the bacterial cell surfaces, the identified proton binding sites were related to carboxyl, phosphate, and hydroxyl/amine groups with pKa values of 4.6 ± 0.7, 6.6 ± 0.01, and 9.7 ± 0.1, respectively, with the corresponding respective intensities of 0.31 ± 0.05, 0.96 ± 0.3, and 1.53 ± 0.3 mmole/g-EPS. The pKa values and intensities of the proton binding sites are the fundamental molecular properties of EPSs that affect the EPS charge, molecular interactions, and metal complexation characteristics. Determination of such properties can advance Derjaguin-Landau-Verwey-Overbeek (DLVO)-based concentration polarization modeling, facilitate the estimation of the osmotic pressure of the EPS concentration polarization layers, and lead to a deeper understanding of the role of metal complexation in membrane fouling.


A Roadmap for Navigating Occupational Exposures for Surgeons: A Special Consideration for the Pregnant Surgeon.
Surgeons are exposed to occupational hazards daily. Risks include chemical, biological, and physical hazards that place providers at risk of serious harm. Departmental policies or written guides to help pregnant surgeons navigate the hospital are lacking. In response to the scarcity in the literature, the authors have summarized current guidelines and recommendations to aid surgeons in making an informed decision. In addition, the authors present a brief narrative of the impact of these exposures during pregnancy and methods of transmission and, where relevant, include specialties that are at risk of these exposures.


Influencing factors of absenteism among first cycle of medical students in the Faculty of Medicine of Sousse.
Student absenteeism is a major concern for higher education and especially for medical studies. This work was conducted to assess the extent of this phenomenon among undergraduate medical students at the Faculty of Medicine of Sousse and to determine whether certain student characteristics affect student absenteeism. We conducted a descriptive cross-sectional study among first and second year of medical study students from the faculty of medicine of Sousse during the second semester of the 2015-2016 academic year using a pretested self-administered questionnaire. The response rate was 80.9%. Of the respondents, 9.6% reported never having attended the lectures. The reason that justified this absenteeism was the boring teaching. Absenteeism was significantly associated with gender (15.7% of male students never attended versus 7.1% of female students, p = 0.015), with the year of study (7.4% of first-year students versus 12.1% of second-year students, p = 0.0001) and the repetition of the year (9.1% of non-repeaters versus 21.1% of repeaters, p = 0.002). Various reasons for missing classes have been identified which suggesting the complexity of this decision. Knowledge of these factors could potentially help university medical teachers to develop innovative teaching strategies that would reduce the rate of absenteeism.


A clinical study on the efficacy of Yiqi Huayu Jiedu decoction for reducing the risk of postoperative recurrence and metastasis of gastric cancer: Protocol for a multicenter, randomized, double-blind, placebo-controlled trial.
Gastric cancer (GC) is one of the top 10 malignant tumors worldwide and poses a great threat to human life and health, the prevention and treatment of which has become the focus and difficulty of medical research. With its unique advantages, traditional Chinese medicine (TCM) is widely used in the prevention and treatment of postoperative recurrence and metastasis of GC as well as the improvement of patients' quality of life. The aim of this study is to elucidate the curative effect and the underlying mechanism of Yiqi Huayu Jiedu (YQHYJD) decoction. This is a prospective, multicenter, randomized controlled trial continuing 3 years. Two hundred ninety-eight eligible patients will be randomly divided into 2 groups, the chemotherapy combined with placebo and the chemotherapy combined with YQHYJD group at a ratio of 1:1. All patients will receive the treatment for 6 months and follow up for 3 years. The primary outcomes are disease-free survival, and 1-year, 2-year, 3-year progression-free survival rate, while the secondary outcomes are tumor makers, TCM syndrome score, quality of life score, overall chemotherapy completion rate, intestinal flora diversity test, immune function (T, B lymphocyte subsets and NK cells) test. The Security index includes blood, urine and stool routine, electrocardiogram, liver function (ALT), and renal function (BUN, Scr). All of these outcomes will be analyzed at the end of the trial. This research will provide the valuable evidence for the efficacy and safety of Yiqi Huayu Jiedu decoction in postoperative GC. Furthermore, it will be helpful to form a higher level of evidence-based medical basis for TCM in the treatment of GC recurrence and metastasis. ChiCTR2000039038.


Pure agraphia in Romaji after left inferior frontal gyrus infarction: A case of selective deficit in syllable-to-grapheme conversion in Japanese.
The Japanese writing system employs two distinct categories of characters: Kana and Kanji. The difference between Kana and Kanji writing corresponds roughly to that between phonological and lexical systems in Western languages. When typing, most Japanese use alphabetical characters based purely on phonological rules. In particular, the Romaji system is used, in which a syllable consists of a single vowel, a consonant-vowel compound (e.g., ka, ki), or a sequence of consonant-y(semivowel)-vowel (e.g., kya, kyu). We describe a right-handed Japanese patient who developed pure agraphia that affected Romaji writing but preserved Kana and Kanji writing and who had a lesion in the left pars opercularis of the inferior frontal gyrus that extended to the anterior precentral gyrus. The patient demonstrated literal paragraphia in spelling Romaji across modalities. Our findings suggested that the patient's agraphia in Romaji after a confined left frontal infarction was manifested by a selective impairment in syllable-to-grapheme conversion.


Stability of SARS-CoV-2 on inanimate surfaces: A review.
The stability of SARS-CoV-2 for varying periods on a wide range of inanimate surfaces has raised concerns about surface transmission; however, there is still no evidence to confirm this route. In the present review, three variables affecting virus stability, namely temperature, relative humidity (RH), and initial virus titer, were considered from different experimental studies. The stability of SARS-CoV-2 on the surfaces of six different contact materials, namely plastic, metal, glass, protective equipment, paper, and fabric, and the factors affecting half-life period was systematically reviewed. The results showed that the half-life of SARS-CoV-2 on different contact materials was generally 2-10 h, up to 5 d, and as short as 30 min at 22 °C, whereas the half-life of SARS-CoV-2 on non-porous surfaces was generally 5-9 h d, up to 3 d, and as short as 4 min at 22 ℃. The half-life on porous surfaces was generally 1-5 h, up to 2 d, and as short as 13 min at 22 °C. Therefore, the half-life period of SARS-CoV-2 on non-porous surfaces is longer than that on porous surfaces, and thehalf-life of the virus decreases with increasing temperature, whereas RH produces a stable negative inhibitory effect only in a specific humidity range. Various disinfection precautions can be implemented in daily life depending on the stability of SARS-CoV-2 on different surfaces to interrupt virus transmission, prevent COVID-19 infections, and avoid over-disinfection. Owing to the more stringent control of conditions in laboratory studies and the lack of evidence of transmission through surfaces in the real world, it is difficult to provide strong evidence for the efficiency of transmission of the contaminant from the surface to the human body. Therefore, we suggest that future research should focus on exploring the systematic study of the entire transmission process of the virus, which will provide a theoretical basis for optimizing global outbreak prevention and control measures.


The absorption of inorganic phosphate from 32P-labeled inositol hexaphosphate by Eriophorum vaginatum.
A scarcity of available phosphorus often limits plant growth, and organic forms of phosphorus are not generally thought to be important direct sources of phosphate for plants. A dominant arctic tundra plant, Eriophorum vaginatum, is able to hydrolyze and absorb phosphate from a naturally occurring organic phosphorus compound at concentrations as low as those found in soil solution and at rates comparable to its ability to absorb inorganic phosphate. Calculations show that in tundra soils, where organic phosphorus is typically the predominant form of phosphorus in soil solution, E. vaginatum's root surface phosphatases may be capable of providing from organic phosphorus up to 69% of the plant's annual phosphorus demand.


Manipulating pyruvate to acetyl-CoA conversion in Escherichia coli for anaerobic succinate biosynthesis from glucose with the yield close to the stoichiometric maximum.
Efficient succinate production in Escherichia coli is attained during anaerobic glucose fermentation in biosynthetic processes combining the reductive branch of the TCA cycle and the glyoxylate bypass. Pyruvate dehydrogenase (PDH) or pyruvate formate lyase (PFL) serves in E. coli as a source of acetyl-CoA, a substrate for the glyoxylate bypass. Depending on enzymes responsible for acetyl-CoA generation, the contribution of the glyoxylate bypass to the anaerobic succinate biosynthesis may vary to support redox balance resulting in diverse maximum achievable yield values. Anaerobic succinate biosynthesis from glucose was studied using E. coli strains with altered expression of genes encoding PFL and PDH. For acetyl-CoA formation by PFL, the yield of 1.32 mol succinate per mole of glucose was achieved with the theoretical value of 1.6 mol/mol. Involvement of PDH in anaerobic acetyl-CoA synthesis increased succinate yield up to 1.49 mol/mol, which is 89.8% of the predicted maximum (1.6(6) mol/mol). The maximum yield of 1.69 mol succinate per mol glucose, amounting to 98.8% of the stoichiometric maximum (1.71 mol/mol), was achieved with the strain possessing PDH as the primary anaerobic source of acetyl-CoA. During high cell density fermentation, the best engineered strain produced high amounts of succinate (570.7 mM) and only small quantities of acetate (11.9 mM).


Investigation of striatal dopamine D2 receptor acquisition following prenatal neuroleptic exposure.
To test the hypothesis that neuroleptic blockade impairs the development of striatal dopamine D2 receptors, pregnant rats were given haloperidol, thiothixene, or trifluoperazine for gestational days 15-18 (short-term exposure) or days 5-20 (long-term exposure). All of the drugs were demonstrated to cross the placenta and enter the fetal brains equally well. Striatal dopamine D2 receptors of the pups were assayed on postnatal day 14. Neither receptor density nor receptor affinity was altered significantly by the short- or long-term prenatal neuroleptic treatment.


Low ambient temperature increases hospital re-admissions for systemic lupus erythematosus in humid subtropical region: a time series study.
Currently, the correlation between ambient temperature and systemic lupus erythematosus (SLE) hospital admissions remains not determined. The aim of this study was to explore the correlation between ambient temperature and SLE hospital admissions in Hefei City, China. An ecological study design was adopted. Daily data on SLE hospital admissions in Hefei City, from January 1, 2007, to December 31, 2017, were obtained from the two largest tertiary hospitals in Hefei, and the daily meteorological data at the same period were retrieved from China Meteorological Data Network. The generalized additive model (GAM) combined with distributed lag nonlinear model (DLNM) with Poisson link was applied to evaluate the influence of ambient temperature on SLE hospital admissions after controlling for potential confounding factors, including seasonality, relative humidity, day of week, and long-term trend. There were 1658 SLE hospital admissions from 2007 to 2017, including 370 first admissions and 1192 re-admissions (there were 96 admissions with admission status not stated). No correlation was observed between ambient temperature and SLE first admissions, but a correlation was found between low ambient temperature and SLE re-admissions (RR: 2.53, 95% CI: 1.11, 5.77) (3.5 °C vs 21 °C). The effect of ambient temperature on SLE re-admissions remained for 2 weeks but disappeared in 3 weeks. Exposure to low ambient temperature may increase hospital re-admissions for SLE, and thus it is important for SLE patients to maintain a warm living environment and avoid exposure to lower ambient temperature.


Postoperative Pain Management After Primary Total Knee Arthroplasty: The Value of Liposomal Bupivacaine.
Multimodal pain protocols have been proposed to achieve improved long-acting postoperative analgesia. Controlling postoperative pain after joint arthroplasty is especially important as it relates to patient satisfaction and outcomes. The purpose of this study was to compare the postoperative pain, time to ambulation, and overall narcotic usage between patients who received either a femoral nerve block with a periarticular bupivacaine injection or a periarticular bupivacaine and extended-release liposomal bupivacaine injection after primary total knee arthroplasty. A total of 597 consecutive primary total knee arthroplasties performed between September 1, 2012 and August 31, 2014 received preoperative celecoxib, oxycodone, and transdermal scopolamine. Intraoperatively, patients either received a single-dose bupivacaine femoral nerve block along with 30-mL 0.25% bupivacaine periarticular injection (group A) or a 60-mL periarticular injection alone (20-mL liposomal bupivacaine, 30-mL 0.25% bupivacaine, and 10-mL saline; group B). The postoperative pain scores, narcotic usage, and time to ambulation were retrospectively collected from the electronic medical record. These outcomes were compared between treatment groups. There were 325 patients in group A compared with 272 in group B during the time frame. There was no difference among age, gender, race, and body mass index between the groups. Group B demonstrated a decreased need for breakthrough pain medication (16.9% vs 36.3% P < .001), decreased pain 12 hours postoperatively (3.2 vs 3.6 P < .003), and an earlier time to ambulation (29.5 hours vs 32.2 hours, P < .017). There was no difference in hospital length of stay (2.8 vs 2.6 days, P = .123). On controlling for demographic factors, patients in group B were able to ambulate 2.3 hours earlier than those in group A (coefficient = -2.3, P = .049). Liposomal bupivacaine resulted in a decrease need for breakthrough pain medication, improved pain scores at 12 hours, and an earlier time to ambulation compared to a combined femoral nerve block and periarticular bupivacaine injection.


(Z)-2-Methylbuten-1-yl(aryl)iodonium trifluoromethanesulfonates containing electron-withdrawing groups on the aryl moiety.
The crystal structures of [(Z)-2-methylbut-1-en-1-yl][4-(trifluoromethyl)phenyl]iodonium trifluoromethanesulfonate, C(12)H(13)F(3)I(+).CF(3)O(3)S(-), (I), (3,5-dichlorophenyl)[(Z)-2-methylbut-1-en-1-yl]iodonium trifluoromethanesulfonate, C(11)H(12)Cl(2)I(+).CF(3)O(3)S(-), (II), and bis[[3,5-bis(trifluoromethyl)phenyl][(Z)-2-methylbut-1-en-1-yl]iodonium] bis(trifluoromethanesulfonate) dichloromethane solvate, 2C(13)H(12)F(6)I(+).2CF(3)O(3)S(-).CH(2)Cl(2), (III), are described. Neither simple acyclic beta,beta-dialkyl-substituted alkenyl(aryl)idonium salts nor a series containing electron-deficient aryl rings have been described prior to this work. Compounds (I)-(III) were found to have distorted square-planar geometries, with each I atom interacting with two trifluoromethanesulfonate counter-ions.


African American race and low income neighborhoods decrease cause specific survival of endometrial cancer: a SEER analysis.
This study analyzed Surveillance, Epidemiology and End Results (SEER) data to assess if socio- economic factors (SEFs) impact on endometrial cancer survival. Endometrial cancer patients treated from 2004-2007 were included in this study. SEER cause specific survival (CSS) data were used as end points. The areas under the receiver operating characteristic (ROC) curve were computed for predictors. Time to event data were analyzed with Kaplan-Meier method. Univariate and multivariate analyses were used to identify independent risk factors. This study included 64,710 patients. The mean follow up time (S.D.) was 28.2 (20.8) months. SEER staging (ROC area of 0.81) was the best pretreatment predictor of CSS. Histology, grade, race/ethnicity and county level family income were also significant pretreatment predictors. African American race and low income neighborhoods decreased the CSS by 20% and 3% respectively at 5 years. This study has found significant endometrial survival disparities due to SEFs. Future studies should focus on eliminating socio-economic barriers to good outcomes.


Antiphospholipid antibodies in 57 children and adolescents with systemic lupus erythematosus.
To investigate the frequencies and behavior of antiphospholipid antibodies in 57 children and adolescents with systemic lupus erythematosus. Anticardiolipin antibodies were investigated by ELISA and lupus anticoagulant antibodies by the international tests recommended. The antiphospholipid antibodies analyses were performed in frozen samples (mean of 5.3 samples per patient obtained during a mean follow-up period of 3 years and 7 months) and on blood samples collected between January 1997 and November 1998 (mean of 2.5 samples per patient during a 2-year follow-up period). The frequencies of antiphospholipid antibodies (anticardiolipin and lupus anticoagulant) were similar in the samples collected prospectively and in the frozen samples (retrospective study): 63.2% and 75.4% respectively. Positivity for these antibodies fluctuated during the follow-up period and was not associated with any clinical or laboratory parameters of lupus erythematosus, including autoantibodies and also including disease activity and/or severity scores. The frequencies of antiphospholipid antibodies in children and adolescents with lupus erythematosus were similar to those observed in adults. The positivity fluctuated during the follow-up and was not correlated with clinical and/or laboratory disease parameters.


Reduction in SLEDAI is associated with improved arterial stiffness in systemic lupus erythematosus.
Lipid abnormalities are an important cause of premature atherosclerosis in patients with systemic lupus erythematosus (SLE). This longitudinal study investigates the changes in lipid profile and arterial stiffness with SLE disease activity index (SLEDAI) reduction.Fifty one female SLE patients with baseline SLEDAI ≥ 6 and SLEDAI reduction >3 at 1-year follow-up were included. Neutrophil-to-lymphocyte ratio (NLR), erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hsCRP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), and mean brachial-ankle pulse wave velocity (baPWV) were measured and compared between baseline and 1-year follow-up. Correlations between inflammation biomarkers, SLEDAI, mean baPWV and lipid profile were assessed.We observed significant decreases in ESR, mean baPWV, TG and TC to HDL-C ratio compared with baseline at 1-year follow up, while HDL-C, hsCRP, and NLR were not significantly changed. Significant correlations were found between the reductions in ESR and TG, and SLEDAI and mean baPWV, with adjustment to age, disease duration, blood pressure, and medications (prednisone, immunosuppressants and ARB/ACEI).SLE patients experiencing SLEDAI reductions showed improvements in arterial stiffness. This finding may provide insight into the beneficial effects of reducing SLEDAI on atherosclerosis risk in SLE.


Modeling sound transmission of human middle ear and its clinical applications using finite element analysis.
We have developed a new finite element (FE) model of human right ear, including the accurate geometry of middle ear ossicles, external ear canal, tympanic cavity, and mastoid cavity. The FE model would be suitable to study the dynamic behaviors of pathological middle ear conditions, including changes of stapedial ligament stiffness, tensor tympani ligament (TTL), and tympanic membrane (TM) stiffness and thickness. Increasing stiffness of stapedial ligament has substantial effect on stapes footplate movement, especially at low frequencies, but less effect on umbo movement. Softer TTL will result in increasing umbo and stapes footplate displacement, especially at low frequencies (f<1000Hz). When the TTL was detached, the vibration amplitude of umbo increased by 6dB at 600Hz and two peaks (300 and 600Hz) were found in the vibration amplitude of stapes footplate. Increasing the stiffness of tensor tympani resulted in a slightly decreased umbo amplitude at very low frequencies (f<500Hz) and significantly decreased displacement up to 12dB at middle frequencies (1000Hz<f<4000Hz). However, the amplitude change of stapes footplate is very sensitive to the TTL stiffness, especially at low frequency (f<1000Hz). The increased stiffness of TM resulted in reduced umbo and stapes footplate displacement at frequencies <1500Hz and increased displacement at frequencies >1500Hz. As (TM) thickness was increased, the umbo displacement was reduced, especially at very low frequencies (f<600Hz). Otherwise, the stapes displacement was reduced at all frequencies.


Molecular analysis of urothelial cancer cell lines for modeling tumor biology and drug response.
The utility of tumor-derived cell lines is dependent on their ability to recapitulate underlying genomic aberrations and primary tumor biology. Here, we sequenced the exomes of 25 bladder cancer (BCa) cell lines and compared mutations, copy number alterations (CNAs), gene expression and drug response to BCa patient profiles in The Cancer Genome Atlas (TCGA). We observed a mutation pattern associated with altered CpGs and APOBEC-family cytosine deaminases similar to mutation signatures derived from somatic alterations in muscle-invasive (MI) primary tumors, highlighting a major mechanism(s) contributing to cancer-associated alterations in the BCa cell line exomes. Non-silent sequence alterations were confirmed in 76 cancer-associated genes, including mutations that likely activate oncogenes TERT and PIK3CA, and alter chromatin-associated proteins (MLL3, ARID1A, CHD6 and KDM6A) and established BCa genes (TP53, RB1, CDKN2A and TSC1). We identified alterations in signaling pathways and proteins with related functions, including the PI3K/mTOR pathway, altered in 60% of lines; BRCA DNA repair, 44%; and SYNE1-SYNE2, 60%. Homozygous deletions of chromosome 9p21 are known to target the cell cycle regulators CDKN2A and CDKN2B. This loci was commonly lost in BCa cell lines and we show the deletions extended to the polyamine enzyme methylthioadenosine (MTA) phosphorylase (MTAP) in 36% of lines, transcription factor DMRTA1 (27%) and antiviral interferon epsilon (IFNE, 19%). Overall, the BCa cell line genomic aberrations were concordant with those found in BCa patient tumors. We used gene expression and copy number data to infer pathway activities for cell lines, then used the inferred pathway activities to build a predictive model of cisplatin response. When applied to platinum-treated patients gathered from TCGA, the model predicted treatment-specific response. Together, these data and analysis represent a valuable community resource to model basic tumor biology and to study the pharmacogenomics of BCa.


Mechanisms of inverse agonism at G-protein-coupled receptors.
Many drugs with important therapeutic actions that had been assumed to be antagonists at G-protein-coupled receptors (GPCRs) have been shown to be inverse agonists. For both basic pharmacology and drug design it is important to understand the mechanisms whereby these drugs achieve their effects. It had been assumed that these drugs achieved their effects by stabilizing an inactive state of the receptor (R) at the expense of a partially activated state (R*). In this article, I consider this and other mechanisms that could explain inverse agonist actions, and conclude that more than one mechanism can apply to inverse agonism at GPCRs.


CNVs of noncoding cis-regulatory elements in human disease.
Genomic rearrangements and copy-number variations (CNVs) are structural aberrations of the human genome which contribute to phenotypic variation as well as human disease. By now it is well accepted that structural aberrations affecting coding regions can have pathogenic effects, however, noncoding variants have only recently come into focus as disease-associated variants. The phenotypes associated with alterations in noncoding regions with regulatory potential can be striking and at the same time confined to a certain tissue/organ. Future studies will elucidate the frequency of these changes which are expected to be higher among conditions that are due to disturbance of complex developmental processes. Integrating these data with the recently published data from the ENCODE project will broaden our view of genes and their regulation and contribute to our understanding of pathomechanism underlying human disease. In this article, we review the recent advances in the identification of genomic rearrangements and CNVs in noncoding regions of the genome and their consequences for human disease.


The detection and characterization of G-proteins in the eyespot of Chlamydomonas reinhardtii.
The presence of G-proteins in the eyespot fraction of Chlamydomonas reinhardtii is shown. This fraction is capable of binding (GTP gamma[35S], possesses the GTPase activity and interacts with antibodies raised against a highly conserved peptide of most G-proteins' alpha-subunit. Cross-reaction with a 24-kDa protein is detected on immunoblots. Using an antiserum prepared from vertebrate beta-subunit peptide, two additional proteins with apparent Mr 21 and 29 kDa could be revealed. The light-dependence of GTPase extraction from eyespot membranes is shown. The results make it possible to suggest the participation of G-proteins in the photosensory transduction chain of Ch. reinhardtii.


Differential Haematobia irritans infestation levels in beef cattle raised in silvopastoral and conventional pasture systems.
The use of silvopastoral systems (SPS) can be a good alternative to reduce the environmental impacts of livestock breeding in Brazil. One of the reasons for its scarce adoption is the lack of information on health and productivity of cattle raised under these conditions. The experiment reported here was designed to compare the infestation by external parasites - the cattle tick (Rhipicephalus microplus), horn fly (Haematobia irritans), and larvae of the botfly (Dermatobia hominis) - in beef cattle raised in a SPS and a conventional pasture system (CPS), evaluated for 24 months. Data on air and soil temperature, solar radiation, wind incidence and water balance were used to characterize the SPS and CPS. R. microplus adult females and D. hominis larvae were counted on the body of each animal to determine the parasites burdens, but we did not find significant differences between the two systems. Horn flies counts on animals' body, and analysis of the horn fly and its pupal parasitoids associated with the dung pats were obtained in the two systems. Horn fly infestation was significantly lower (p=0.01) in the SPS (13.17±3.46) in comparison with the CPS (24.02±4.43). In SPS and CPS, respectively, the mean densities of pupae of H. irritansin dung pats were 9.8 and 10.7; the mean density of adults of H. irritans, 3.7 and 3.5; and the density of its pupal parasitoids were 20.5 and 5.4. The effect of production system was significant (p<0.05) only for the occurrence of pupal parasitoids of the horn fly, where the greatest occurrences of these natural enemies were in the SPS. These data indicate that natural enemies were able to control, at least partially, the horn fly populations in the cattle.


Balloon-Occluded Transarterial Chemoembolization: In Which Size Range Does It Perform Best? A Comparison of Its Efficacy versus Conventional Transarterial Chemoembolization, Using Propensity Score Matching.
The aim of this multicenter comparison of balloon-occluded transarterial chemoembolization (B-TACE) versus conventional TACE (cTACE) in treating hepatocellular carcinoma (HCC) was to assess in which size range the 2 techniques offered higher complete response (CR) and objective response (OR) rates in a single session, and to evaluate the possibility of using B-TACE to reduce the need for re-treatment. 325 patients were retrospectively evaluated: 91 patients in the B-TACE group (22 with cTACE [B-cTACE] and 69 with drug-eluting microsphere TACE [B-DEM-TACE]) and 234 in the cTACE group. The results were compared according to tumor size: (A) <30 mm, (B) 30-50 mm, and (C) >50 mm; OR and CR rates after the first session and the number of TACE re-interventions within a 6-month period were also evaluated using propensity score matching (PSM). The best target ORs were very high (93.2%) and similar between the 2 treatments both before (94.4% for cTACE and 90.1% for B-TACE) and after PSM (94.5% for cTACE and 90.1%; p = 0.405), with slightly better results for the cTACE cohort probably due to better cTACE effectiveness in smaller lesions. In lesions <30 mm, cTACE obtained a slightly higher CR rate than B-TACE (61.9 vs. 56.3%, p = 0.680), whereas in intermediate-sized HCCs (30-50 mm), B-TACE showed a significant superiority in achieving a CR (72.3 vs. 54.1%, respectively; p = 0.047). In larger lesions (>50 mm), cTACE and B-TACE performed equally, with a poor CR rate (22.6 vs. 23.1%, respectively; p = 1.000). These results were additionally confirmed using PSM. The patients treated with B-TACE had a significantly lower re-treatment rate than the cTACE cohort (12.1 vs. 26.9%, respectively; p = 0.005). B-cTACE and B-DEM-TACE demonstrated similar ORs, with a slightly better CR rate for B-cTACE (68.2 vs. 56.5%, respectively; p = 0.456). In HCCs of 30-50 mm, B-TACE should be preferred to cTACE, whereas in smaller nodules (<30 mm), cTACE can suffice in achieving a good CR rate. The statistically significant lower re-treatment rate of the B-TACE cohort after a single procedure reduced the risk of complications due to multiple TACE, which could worsen the patient prognosis.


Fluorescent properties of organic carbon in cave dripwaters: effects of filtration, temperature and pH.
For the first time the specific fluorescent characteristics of organic carbon (OC) in sequentially filtered cave dripwater samples have been studied and the proportions of organic carbon in each size fraction quantified. We examined the effects of pH, temperature and filtration on the fluorescent properties of OC sampled from four drip points in different seasons. Dripwaters were sampled from both normal (pH 7.5-8.5) and hyper-alkaline (pH 9-13) drip points in Poole's Cavern, Buxton, UK, which provides a model system for understanding the effects of pH on the chemical properties of OC. At high-pH values, charge stabilisation of OC is greatly enhanced, resulting in 10-20 times more coarse colloidal and particulate (>100 nm) organic carbon than in lower pH dripwaters; indicating that destabilisation (e.g. charge shielding) of colloidal OC is an important process control on the transmission of OC in cave dripwaters at near-neutral pH. OC fluorescence in high-pH dripwaters exhibited a high degree of pH sensitivity between pH 10 and 12, consistent with substantial changes in the coordination or neighbouring environment of fluorescent acidic functional groups. Inner-filter effects (IFE) associated with the coarse colloidal and particulate fraction of OM mask the true fluorescent signal, so that size fractionation is necessary to obtain a signal which is correlated with the concentration of organic carbon. Fluorescence intensities in the samples studied were best correlated with organic carbon with a dimension <100 nm. These results have important implications for the use of fluorescence as a tracer in hydrogeological studies.


The chromaffin granule proton pump and calcium-dependent exocytosis in bovine adrenal medullary cells.
Calcium-dependent exocytosis in 'leaky' bovine adrenal medullary cells has a requirement for Mg-ATP. One possibility is that exocytosis depends in some way on the operation of the ATP-dependent proton pump that serves to maintain the core of the secretory vesicles both acid and at a positive potential with respect to the cytosol. This possibility has been tested in 'leaky' cells by monitoring exocytosis under conditions where the secretory vesicle pH and potential gradients are measured in situ. The results show rather clearly that exocytosis can persist, with unchanged Ca-activation kinetics, in the virtual absence both of a difference in pH between the cytosol and secretory vesicle core and also of a difference in potential across the vesicle membrane. The results do not, however, exclude a small modulating effect of vesicle pH or potential on exocytosis and shed no light on whether or not the plasma membrane potential, which is maintained close to zero in these experiments, influences exocytosis.


On the intrinsic nature of viral pathogenesis: The assumption of a Darwinian paradigm to describe COVID-19 pandemic.
Our hypothesis about evolution of the COVID-19 pandemic foresees an inverse relation between infectivity (R0) and lethality (L) of SARS-CoV-2. The above parameters are driven by a continuing mutation process granting the virus a clear survival advantage over virulence. For interpreting this relation we adopted a simple equation, R0 × L ≈ k, by which R0 and L depend upon a constant k, that corresponds to an intrinsic property of the viral species involved. The hypothesis was verified by following changes of the R0 and L terms of the formula in the different variants of SARS-CoV-2 that progressively appeared. A further validation came when the equation was applied to pandemic and epidemic influenza type A viruses, Ebola virus and measles virus. We believe this equation that considers virus biology in Darwinian terms could be extremely useful to better face infectious viral threats and validate virus-host molecular interactions relevant to viral pathogenesis.


Fully automated analysis of estrogens in environmental waters by in-tube solid-phase microextraction coupled with liquid chromatography-tandem mass spectrometry.
A simple, rapid and sensitive method for the determination of five estrogens, estrone, 17beta-estradiol, estriol, ethynyl estradiol, and diethylstilbestrol, was developed using a fully automated method consisting of in-tube solid-phase microextraction (SPME) coupled with liquid chromatography-tandem mass spectrometry (LC/MS/MS). These estrogens were separated within 8 min by HPLC using an XDB-C8 column and 0.01% ammonia/acetonitrile (60/40, v/v) at a flow rate of 0.2 mL/min. Electrospray ionization conditions in the negative ion mode were optimized for MS/MS detection of the estrogens. The optimum in-tube SPME conditions were 20 draw/eject cycles of 40 microL of sample using a Supel-Q PLOT capillary column as an extraction device. The extracted compounds were easily desorbed from the capillary by passage of the mobile phase, and no carryover was observed. Using the in-tube SPME LC/MS/MS method, good linearity of the calibration curve (r > or = 0.9996) was obtained in the concentration range from 10 to 200 pg/mL for all compounds examined. The limits of detection (S/N= 3) of the five estrogens examined ranged from 2.7 to 11.7 pg/mL. The in-tube SPME method showed 34-90-fold higher sensitivity than the direct injection method (5 microL injection). This method was applied successfully to the analysis of environmental water samples without any other pretreatment and interference peaks. Several surface water and wastewater samples were collected from the area around Asahi River, and estriol was detected at 35.7 pg/mL in the effluent of a sewage treatment plant. The recoveries of estrogens spiked into river waters were above 86%, except for estriol, and the relative standard deviations were below 0.9-8.8%.


Rabbit antipeptide antibodies against restricted domains of the histocompatibility complex.
The work reported here concerns the specificity of four antibodies elicited by synthetic peptides corresponding to three domains of the HLA-B7 glycoprotein, and one of the beta 2 microglobulin. One of the four peptides had been previously investigated, but the data obtained by its elicited antibodies were uncomplete. Of the three HLA-B7 peptides assayed, one was unable to raise an immune response. The other two produced antibodies in good titer that reacted with the antigen peptide, but were unable to recognize antigenic determinants when tested on membrane glycoproteins solubilized from human lymphoblastoid cells. In contract, the antibody elicited by the only fragment from the beta 2microglobulin recognized the native beta 2microglobulin molecule as well as HLA/beta 2m complexes, and reacted with intact human cells, as determined by ELISA and by FACS analysis. This peptide, which contains one of the most hydrophylic fragment of the whole molecule, is likely an important antigenic site, since it is also recognized by traditional antisera raised against native beta 2microglobulin.


An integrative approach to investigate the respective roles of single-nucleotide variants and copy-number variants in Attention-Deficit/Hyperactivity Disorder.
Many studies have attempted to investigate the genetic susceptibility of Attention-Deficit/Hyperactivity Disorder (ADHD), but without much success. The present study aimed to analyze both single-nucleotide and copy-number variants contributing to the genetic architecture of ADHD. We generated exome data from 30 Brazilian trios with sporadic ADHD. We also analyzed a Brazilian sample of 503 children/adolescent controls from a High Risk Cohort Study for the Development of Childhood Psychiatric Disorders, and also previously published results of five CNV studies and one GWAS meta-analysis of ADHD involving children/adolescents. The results from the Brazilian trios showed that cases with de novo SNVs tend not to have de novo CNVs and vice-versa. Although the sample size is small, we could also see that various comorbidities are more frequent in cases with only inherited variants. Moreover, using only genes expressed in brain, we constructed two "in silico" protein-protein interaction networks, one with genes from any analysis, and other with genes with hits in two analyses. Topological and functional analyses of genes in this network uncovered genes related to synapse, cell adhesion, glutamatergic and serotoninergic pathways, both confirming findings of previous studies and capturing new genes and genetic variants in these pathways.


[Status epilepticus].
Status epilepticus (SE) is a medical emergency. For diagnostic purposes EEG is mandatory when motor phenomena are absent or when a single seizure evolves into SE with impaired consciousness. The EEG may show focal or generalized status patterns, which must be distinguished from encephalopathies. Initially benzodiazepines are recommended; lorazepam is the drug of choice. When the SE persists, phenytoin, valproate, levetiracetam, lacosamide, and phenobarbital are administered. The choice depends on the underlying comorbidities. In this phase, only phenytoin is licensed. A generalized tonic-clonic status which is refractory is then treated with anesthetics including midazolam, disoprivan, or thiopental. The goal is to achieve burst suppression in the EEG and coadministration of antiepileptic drugs.


Tendon vibration during submaximal isometric strength and postural tasks.
To establish the effect of tendon vibration (TV) on steady submaximal strength and static balance control, 29 women performed isometric plantarflexions at 10, 20, 30 and 50% of MVC and postural tasks of increasing difficulty (Normal Quiet Stance, NQS, Sharpened Tandem Stance and One Leg Stance) with vibrators (80 Hz) applied to the Achilles tendon. Both tasks were performed under four conditions (10 s each): eyes open, eyes closed, eyes closed with TV, eyes open with TV. During the isometric tasks, the application of TV increased the plantarflexion torque at 20 and 30% of MVC, accompanied by a greater (p < 0.001) activation of agonists (Medial Gastrocnemius, MGAS and Soleus, SOL), as well as a greater (p < 0.05) coactivation of the antagonist (tibialis anterior, TA). Non-significant differences were observed at 10 and 50% of MVC. During posture, TV resulted in a backward displacement of the Centre of Pressure only for NQS and an increase (p < 0.01) in EMG activity of the ankle muscles in all balance tasks. The MGAS contraction during TV application was confirmed (by ultrasonography) at ten participants by an increase of the pennation angle and decrease of its fascicle length (p < 0.05). The vibration-induced muscle excitation and accompanying increase in motor output, probably due to excitatory Ia afferent input, was confirmed during strength and postural tasks. However, motor output attenuates when the magnitude of central drive to the ankle muscles increases.


Association of MBP peptides with Hsp70 in normal appearing human white matter.
Multiple Sclerosis is an autoimmune disease directed against myelin proteins. The etiology of MS is poorly defined though, with no definitive causative agent yet identified. It has been hypothesized that MS may be a multifactorial disease resulting in the same end product: the destruction of myelin by the immune system. In this report we describe a potential role for heat shock proteins in the pathogenesis of MS. We isolated Hsp70 from the normal appearing white matter of both MS and normal human brain and found this was actively associated with, among other things, immunodominant MBP peptides. Hsp70-MBP peptide complexes prepared in vitro were shown to be highly immunogenic, with adjuvant-like effects stimulating MBP peptide-specific T cell lines to respond to normally sub-optimal concentrations of peptide. This demonstration of a specific interaction between Hsp70 and different MBP peptides, coupled with the adjuvanticity of this association is suggestive of a possible role for Hsp70 in the immunopathology associated with MS.


Antimycobacterial activity of medicinal plants used by the Mayo people of Sonora, Mexico.
Tuberculosis (TB) is an infectious disease mainly caused by Mycobacterium tuberculosis (Mtb), which generates 9 million new cases worldwide each year. The Mayo ethnicity of southern Sonora, Mexico is more than 2000 years old, and the Mayos possess extensive knowledge of traditional medicine. To evaluate the antimycobacterial activity levels of extracts of medicinal plants used by the Mayos against Mtb and Mycobacterium smegmatis (Msm) in the treatment of TB, respiratory diseases and related symptoms. A total of 34 plant species were collected, and 191 extracts were created with n-hexane, dichloromethane, ethyl acetate (EtOAc), methanol and water. Their minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were determined against Mtb H37Rv using the microplate alamar blue assay (MABA) and against Msm using the resazurin microplate assay (REMA) at 6 and 2 days of exposure, respectively, and at concentrations of 250-1.9µg/mL (n-hexane extracts) and 1000-7.81µg/mL (extracts obtained with dichloromethane, EtOAc, methanol and water). Rhynchosia precatoria (Willd.) DC. (n-hexane root extract), Euphorbia albomarginata Torr. and A. Gray. (EtOAc shoot extract) and Helianthus annuus L. (n-hexane stem extract) were the most active plants against Mtb H37Rv, with MICs of 15.6, 250, 250µg/mL and MBCs of 31.25, 250, 250µg/mL, respectively. R. precatoria (root) was the only active plant against Msm, with MIC and MBC values of ≥250µg/mL. None of the aqueous extracts were active. This study validates the medicinal use of certain plants used by the Mayo people in the treatment of TB and related symptoms. R. precatoria, E. albomarginata and H. annuus are promising plant sources of active compounds that act against Mtb H37Rv. To our knowledge, this is the first time that their antimycobacterial activity has been reported. Crude extracts obtained with n-hexane, EtOAc and dichloromethane were the most active against Mtb H37Rv.


An objective comparison of two pulse oximetry sensors with different adhesive systems on healthy human volunteers based on biophysical assessments.
Medical Adhesive Related Skin Injuries can arise from topically applied medical devices, especially in those with fragile skin, including the elderly and premature infants. The purpose of this study was to compare gentleness and reapplication of two pulse oximetry sensors (OxySoftN and MaxN, Medtronic, Boulder, CO). Eighteen healthy subjects aged 65 years and older were enrolled in the gentleness trial, and 20 healthy subjects (18-69 years) were enrolled in the reapplication trial. For the gentleness trial, trans-epidermal water loss (TEWL) measurements were made at five sites on each forearm at three time points (baseline [T0], 4-h postinitial wear [T1], 4-h postsecond wear [T2]). Total amount of protein adhered to each device was also determined. For the reapplication trial, a series of 180° peel tests were performed to observe the forces required to detach the sensor from the skin. TEWL rates in the tail region were significantly greater with MaxN compared to OxySoftN at T1 (p < 0.05). Both were significantly greater than control (p < 0.05). Further, protein analysis revealed that the amount of protein removed was significantly less with OxySoftN compared to MaxN (p < < 0.0001). Differences in loss of adhesion of the tail region between the two sensors were demonstrated, with OxySoftN depreciating at a much slower rate compared with MaxN. The OxySoftN sensor appears to be gentle, even on fragile skin, based on reduced strain on the skin during removal. Further, it demonstrated the ability to withstand several reapplications without functional loss in adhesion.


Phylogenetic distance affects the artificial microbial consortia's effectiveness and colonization during the bioremediation of polluted soil with Cr(VI) and atrazine.
Soils co-contaminated with heavy metals and organic pollutants are common and threaten the natural environment and human health. Although artificial microbial consortia have advantages over single strains, the mechanism affecting their effectiveness and colonization in polluted soils still requires determination. Here, we constructed two kinds of artificial microbial consortia from the same or different phylogenetic groups and inoculated them into soil co-contaminated with Cr(VI) and atrazine to study the effects of phylogenetic distance on consortia effectiveness and colonization. The residual concentrations of pollutants demonstrated that the artificial microbial consortium from different phylogenetic groups achieved the highest removal rates of Cr(VI) and atrazine. The removal rate of 400 mg/kg atrazine was 100%, while that of 40 mg/kg Cr(VI) was 57.7%. High-throughput sequence analysis showed that the soil bacterial negative correlations, core genera, and potential metabolic interactions differed among treatments. Furthermore, artificial microbial consortia from different phylogenetic groups had better colonization and a more significant effect on the abundance of native core bacteria than consortia from the same phylogenetic group. Our study highlights the importance of phylogenetic distance on consortium effectiveness and colonization and offers insight into the bioremediation of combined pollutants.


Atg1 kinase activity links PAS dissolution to balanced Atg8 conjugation.
Atg1 phosphoregulates different steps and factors in autophagy. Schreiber et al. report in Molecular Cell on the cell-free identification of a negative feedback ejection of Atg1 from the pre-autophagosomal structure (PAS), followed by positive feedback recruitment of Atg1 to phagophore-resident Atg8-PE, followed by yet another, negative feedback inhibition of the Atg8 conjugation machinery.


A redox modulated ratiometric fluorometric method based on the use of dual-color carbon dots for determination of the activity of enzymes participating in ascorbic acid-related reactions.
A turn-on ratiometric fluorescent assay is described for the determination of the activity of enzymes participating in ascorbic acid-forming reactions. Blue-emitting carbon dots (bCDs; with excitation/emission wavelength at 380/450 nm) serve as fluorescent indicator. Their fluorescence is reduced by Fe3+ ions via an inner filter effect. Yellow-emitting CDs (yCDs; with excitation/emission wavelength at 380/550 nm) serve as internal reference because their fluorescence is insensitive to Fe3+. Upon exposure to ascorbic acid (AA), Fe3+ is reduced to Fe2+. Hence, the fluorescence of the bCDs is restored. Thus, enzymes participating in AA-related reactions such as α-glucosidase (α-Glu) and alkaline phosphatase (ALP) can be determined. α-Glu activity was quantified in the range from 0.13 to 6.70 U mL-1, and ALP activity was determined between 2.0 and 130 U L-1. Endowed with excellent sensitivity, selectivity and low background signals, the method may also be used to screen the inhibitors of α-Glu and ALP. Graphical abstractSchematic representation of a redox modulated ratiometric fluorometric method based on the use of dual-color carbon dots for determination of the activity of enzymes participating in ascorbic acid-related reactions. Blue-emitting carbon dots (bCDs) serve as fluorescent indicator while yellow-emitting CDs (yCDs) serve as internal reference.


Poor nutritional status but not cognitive or functional impairment per se independently predict 1 year mortality in elderly patients with hip-fracture.
Hip fractures are strongly associated with mortality in the elderly. Studies investigating predisposing factors have suggested a negative impact of poor nutritional, cognitive and functional status on patient survival, however their independent prognostic impact as well as their interactions remain undefined. This study aimed to determine whether poor nutritional status independently predicts 1 year post-fracture mortality after adjusting for cognitive and functional status and for other clinically relevant covariates. 1211 surgically treated hip fracture elderly (age ≥ 65) patients consecutively admitted to the Orthopaedic Surgery Unit of the "Azienda Sanitaria Universitaria Integrata Trieste" (ASUITs), Cattinara Hospital, Trieste, Italy and managed by a dedicated orthogeriatric team. Pre-admission nutritional status was evaluated by Mini Nutritional Assessment (MNA) questionnaire, cognitive status by Short Portable Mental Status Questionnaire (SPMSQ) and functional status by Activity of Daily Living (ADL) questionnaire. All other clinical data, including comorbidities, type of surgery, post-operative complications (delirium, deep vein thrombosis, cardiovascular complications, infections, need for blood transfusions) were obtained by hospital clinical records and by mortality registry. Poor nutritional status (defined as MNA ≤23.5), increased cognitive and functional impairment were all associated with 3-, 6- and 12 month mortality (p < 0.001). Both cognitive and functional impairment were associated with poor nutritional status (p < 0.001). Logistic regression analysis demonstrated that the association between nutritional status and 3-, 6- and 12- month mortality was independent of age, gender, comorbidities, type of surgery and post-operative complications as well as of cognitive and functional impairment (p < 0.001). In contrast, the associations between mortality and cognitive and functional impairment were independent (p < 0.001) of demographic (age, gender) and clinical covariates but not of malnutrition. Kaplan-Meier analysis showed a lower mean survival time (p < 0.001) in patients with poor nutritional status compared with those well-nourished. In hip fracture elderly patients, poor nutritional status strongly predicts 1 year mortality, independently of demographic, functional, cognitive and clinical risk factors. The negative prognostic impact of functional and cognitive impairment on mortality is mediated by their association with poor nutritional status.


The volar carpal ligament.
The volar carpal ligament, or superficial part of the flexor retinaculum, is described. A triangular area is identified on the ulnar side of the flexor retinaculum.


Reproducibility analysis of automated deep learning based localisation of mandibular canals on a temporal CBCT dataset.
Preoperative radiological identification of mandibular canals is essential for maxillofacial surgery. This study demonstrates the reproducibility of a deep learning system (DLS) by evaluating its localisation performance on 165 heterogeneous cone beam computed tomography (CBCT) scans from 72 patients in comparison to an experienced radiologist's annotations. We evaluated the performance of the DLS using the symmetric mean curve distance (SMCD), the average symmetric surface distance (ASSD), and the Dice similarity coefficient (DSC). The reproducibility of the SMCD was assessed using the within-subject coefficient of repeatability (RC). Three other experts rated the diagnostic validity twice using a 0-4 Likert scale. The reproducibility of the Likert scoring was assessed using the repeatability measure (RM). The RC of SMCD was 0.969 mm, the median (interquartile range) SMCD and ASSD were 0.643 (0.186) mm and 0.351 (0.135) mm, respectively, and the mean (standard deviation) DSC was 0.548 (0.138). The DLS performance was most affected by postoperative changes. The RM of the Likert scoring was 0.923 for the radiologist and 0.877 for the DLS. The mean (standard deviation) Likert score was 3.94 (0.27) for the radiologist and 3.84 (0.65) for the DLS. The DLS demonstrated proficient qualitative and quantitative reproducibility, temporal generalisability, and clinical validity.


Sodium alginate-sodium hyaluronate-hydrolyzed silk for microencapsulation and sustained release of kidney tea saponin: The regulation of human intestinal flora in vitro.
Kidney tea saponin (KTS) exhibits considerable efficacy in lowering glucose levels; however, it does not have widespread applications owing to its low intestinal utilization. Therefore, in the present study, we prepared sodium alginate (SA)/sodium hyaluronate (HA)/hydrolyzed silk (SF) gel beads for the effective encapsulation and targeted intestinal release of KTS. The gel beads exhibited an encapsulation rate of 90.67 % ± 0.27 % and a loading capacity of 3.11 ± 0.21 mg/mL; furthermore, the release rate of KTS was 95.46 % ± 0.02 % after 8 h of simulated digestion. Fourier transform infrared spectroscopy revealed that the hydroxyl in SA/HA/SF-KTS was shifted toward the strong peak; this was related to KTS encapsulation. Furthermore, scanning electron microscopy revealed that the gel bead space network facilitates KTS encapsulation. In addition, the ability of KTS and the gel beads to inhibit α-amylase (IC50 = 0.93 and 1.37 mg/mL, respectively) and α-glucosidase enzymes (IC50 = 1.17 and 0.93 mg/mL, respectively) was investigated. In vitro colonic fermentation experiments revealed that KTS increased the abundance of Firmicutes/Bacteroidetes and butyric acid-producing bacteria. The study showed that the developed gel-loading system plays a vital role in delivering bioactive substances, achieving slow release, and increasing the abundance and diversity of intestinal flora.