Parental etiological explanations and longitudinal medication use for youths with attention deficit hyperactivity disorder.
Due to the need to increase understanding of factors associated with medication usage for youth with ADHD, this study examined parental explanatory etiologies in relationship to psychotropic medication use in a sample of youth who met criteria for ADHD and utilized outpatient specialty mental health services in the previous year. When examined cross-sectionally, medication usage was positively associated with parental explanatory etiologies related to physical causes and negatively associated with those involving sociological causes. Longitudinal analyses did not show a significant effect of Time 1 parental explanatory etiologies on the slope of medication use, suggesting that the relationship between Time 1 parental explanatory etiologies and medication usage remains stable over time for those who have had past year involvement with outpatient specialty mental health services.


RP-HPLC assay of doxycycline in human saliva and gingival crevicular fluid in patients with chronic periodontal disease.
A reversed-phased HPLC method with fluorescence detection was optimized and validated for determination of DOXY in human saliva and gingival crevicular fluid (GCF) with tetracycline as internal standard. Single step extraction with acetonitrile for both types of samples was performed. The separation was achieved at Zorbax Extend-C18 analytical column at 30°C. Mobile phase was consisted of an aqueous phase containing magnesium acetate, ammonium acetate, Na₂EDTA, triethyl-ammonium acetate buffered to pH 7.5 with ammonium hydroxide solution and acetonitrile. The volume ratio of the buffered water mixture of salts and acetonitrile was 86:14. Fluorescence detector was set at λex=380 nm and λem=520 nm. Under the optimized experimental conditions, good linearity was found in the range of 5.0-250.0 ng/mL for GCF with LOD of 1.63 ng/mL and LOQ of 4.93 ng/mL and 20.0-500.0 ng/mL for saliva with LOD of 6.36 ng/mL and LOQ of 19.28 ng/mL. This method was successfully applied for determination of DOXY in saliva and GCF obtained from patients with chronic periodontal disease.


Complex coacervation of collagen hydrolysate extracted from leather solid wastes and chitosan for controlled release of lavender oil.
In the world, approximately 600,000 metric tonnes of chromium-containing solid wastes are generated by the leather industry each year. Environmental concerns and escalating landfill costs are becoming increasingly serious problems to the leather industry and seeking solutions to these problems is a prime concern in much research today. In this study, solid collagen-based protein hydrolysate was isolated from chromium-tanned leather wastes and its chemical properties were determined. Microcapsules of collagen hydrolysate (CH) - chitosan (C) crosslinked with glutaraldehyde (GA) containing Lavender oil (LO) were prepared by complex coacervation method. The effects of various processing parameters, including the CH to C ratio, LO content, and GA, on the oil load (%), oil content (%), encapsulation efficiency (%) and release rate of LO from microcapsules were investigated. As the ratio of C present in the CH/C mixture and crosslinking density increased, the release rate of LO from microcapsules slowed down. Optical and scanning electron microscopy images illustrated that the LO microcapsules were spherical in shape. Fourier transform infrared spectroscopy (FTIR) studies confirmed that there was no significant interaction between CH/C complex and LO.


Molecular epidemiological survey, genetic characterization and phylogenetic analysis of Anaplasma ovis infecting sheep in Northern Egypt.
Anaplasma ovis is the most common etiologic agent of ovine anaplasmosis, mainly transmitted by ticks. The present study aimed to determine the molecular prevalence of A. ovis in sheep from Egypt and assessed the associated risk factors. The study was conducted, between January and December 2020, in four governorates situated in Northern Egypt. Blood samples from 355 asymptomatic sheep were collected and examined by the use of PCR specific to A. ovis. Diversity analysis and phylogenetic study based on partial msp4 gene sequence were performed on revealed A. ovis DNA. Overall, the molecular prevalence rate of A. ovis was 15.5% and the highest rate was observed in Kafr ElSheikh governorate (16.8%). Statistical analysis revealed that A. ovis infection was significantly related to sheep gender and to tick infestation. The risk factors that were found to be associated with A. ovis infection in exposed sheep were: female sex (OR=2.6, 95%CI: 1.13-6.12), and infestation with ticks (OR=2.1, 95%CI: 1.11-3.79). The analysis of A. ovis msp4 sequences revealed two different genotypes classified in the Old World sub-cluster with other Egyptian isolates. Investigation on prevalence, risk factors and genetic variability of A. ovis in sheep reported in this study is important for the implementation of control programs. Further studies are needed to determine the vectors and reservoirs of A. ovis in Egyptian small ruminants and to identify the real economic impact of A. ovis infection on the country.


Prevalence and correlates of indoor tanning among US adults.
Little is known about the prevalence of indoor tanning among the US general adult population. This study sought to: (1) describe the prevalence of indoor tanning throughout adulthood; (2) identify demographic and psychosocial correlates of indoor tanning; and (3) determine whether these correlates vary by age group. This study used data from the 2005 National Health Interview Survey, an annual health survey of the US adult population. Indoor tanning rates were higher among individuals who were young, white, and female. Rates of indoor tanning in the last year varied from 20.4% for those aged 18 to 29 years to 7.8% for those aged 65 years and older. A variety of demographic, health, and behavioral health risk factors correlated with indoor tanning. The study design was cross-sectional and all data were self-reported. Health care providers should address indoor tanning as a health risk factor across the lifespan.


Reoperation by anterior perineal approach for missed puborectalis.
Poor postoperative continence in patients operated for high imperforate anus may result from an inadequate bowel pull-through behind the puborectal muscle. Between 1979 and 1983, we used the anterior perineal approach for reoperations in five such cases (3 males, 2 females). In all of them, preoperative continence was socially unacceptable. Each time it was possible to identify a partially or totally missed puborectal muscle. Although some complications occurred postoperatively, all patients acquired a socially acceptable level of continence with a mean follow-up of 4.5 years. Preoperative and postoperative rectal manometries are presented. The anterior perineal approach not only provides adequate exposure of the urethra and puborectal muscle, but also has the advantage of operating through an area that has not been previously dissected.


Optimization of conditions for the glycosyltransferase activity of penicillin-binding protein 1a from Thermotoga maritima.
Cell wall biosynthesis is a key target for antibacterial drugs. The major constituent of the bacterial wall, peptidoglycan, is a netlike polymer responsible for the size and shape of the cell and for resisting osmotic pressure. It consists of glycan chains of repeating disaccharide units cross-linked through short peptide chains. Peptidoglycan assembly is catalyzed by the periplasmic domain of bifunctional class A penicillin-binding proteins. Cross-linking of the peptide chains is catalyzed by their transpeptidase module, which can be inhibited by the most widely used antibiotics, the β-lactams. In contrast, no drug in clinical use inhibits the polymerization of the glycan chains, catalyzed by their glycosyltransferase module, although it is an obvious target. We report here the purification of the ectodomain of the class A penicillin-binding protein 1a from Thermotoga maritima (Tm-1a*), expressed recombinantly in Escherichia coli. A detergent screen showed that detergents with shorter aliphatic chains were better solubilizers. Cyclohexyl-hexyl-β-D-maltoside-purified Tm-1a* was found to be monomeric and to have improved thermal stability. A miniaturized, multiwell continuous fluorescence assay of the glycosyltransferase activity was used to screen for optimal reaction conditions. Tm-1a* was active as a glycosyltransferase, catalyzing the formation of glycan chains up to 16 disaccharide units long. Our results emphasize the importance of the detergent in preparing a stable monomeric ectodomain of a class A penicillin-binding protein. Our assay could be used to screen collections of compounds for inhibitors of peptidoglycan glycosyltransferases that could serve as the basis for the development of novel antibiotics.


Antiviral immunity triggered by infection-induced host transposable elements.
Host silencing of transposable elements (TEs) is critical to prevent genome damage and inappropriate inflammation. However, new evidence suggests that a virus-infected host may re-activate TEs and co-opt them for antiviral defense. RNA-Seq and specialized bioinformatics have revealed the diversity of virus infections that induce TEs. Furthermore, studies with influenza virus have uncovered how infection-triggered changes to the SUMOylation of TRIM28, an epigenetic co-repressor, lead to TE de-repression. Importantly, there is a growing appreciation of how de-repressed TEs stimulate antiviral gene expression, either via cis-acting enhancer functions or via their recognition as viral mimetics by innate immune nucleic acid sensors (e.g. RIG-I, mda-5 and cGAS). Understanding how viruses trigger, and counteract, TE-based antiviral immunity should provide insights into pathogenic mechanisms.


Aromatization and 19-hydroxylation of androgens by rat brain cytochrome P-450.
The oxidative metabolism of androgens in the rat brain includes aromatization preceded by the requisite 19-hydroxylation. We have examined the transformation of [19-C3H3]androstenedione and [4-14C]testosterone by the semipurified cytochrome P-450 fraction of the rat brain. [19-C3H3]Androstenedione generated tritiated water and formic acid in a ratio of 8 to 1 indicating that 19-hydroxylation in the brain far exceeds that necessary for aromatization. This was confirmed by the results of the 14C-testosterone incubation in which the 14C labeled 19-hydroxy and 19-oxo derivatives which were isolated exceeded the yield of 14C-estrogens by several fold. Thus the rat brain has the capacity to form in situ 19-hydroxylated androgens which are not available to it from the circulation.


Formulation of the multi-hit model with a non-Poisson distribution of hits.
We proposed a formulation of the multi-hit single-target model in which the Poisson distribution of hits was replaced by a combination of two distributions: one for the number of particles entering the target and one for the number of hits a particle entering the target produces. Such an approach reflects the fact that radiation damage is a result of two different random processes: particle emission by a radiation source and interaction of particles with matter inside the target. Poisson distribution is well justified for the first of the two processes. The second distribution depends on how a hit is defined. To test our approach, we assumed that the second distribution was also a Poisson distribution. The two distributions combined resulted in a non-Poisson distribution. We tested the proposed model by comparing it with previously reported data for DNA single- and double-strand breaks induced by protons and electrons, for survival of a range of cell lines, and variation of the initial slopes of survival curves with radiation quality for heavy-ion beams. Analysis of cell survival equations for this new model showed that they had realistic properties overall, such as the initial and high-dose slopes of survival curves, the shoulder, and relative biological effectiveness (RBE) In most cases tested, a better fit of survival curves was achieved with the new model than with the linear-quadratic model. The results also suggested that the proposed approach may extend the multi-hit model beyond its traditional role in analysis of survival curves to predicting effects of radiation quality and analysis of DNA strand breaks. Our model, although conceptually simple, performed well in all tests. The model was able to consistently fit data for both cell survival and DNA single- and double-strand breaks. It correctly predicted the dependence of radiation effects on parameters of radiation quality.


Neuroethologically delineated differences in the seizure behavior of synapsin 1 and synapsin 2 knock-out mice.
The highly homologous nerve terminal phosphoproteins synapsin I and synapsin II have been linked to the pathogenesis of epilepsy through associations between synapsin gene mutations and epileptic disease in humans and to the observation of handling induced seizures in mice genetically depleted of one or both of these proteins. Whereas seizure behavior in mice lacking both synapsin I and synapsin II is well characterized, the seizure behavior in mice lacking either is less well studied. Through so called neuroethologically based analyses of fully established seizure behavior in Synapsin 1 and 2 knock-out mice (Syn1KO and Syn2KO mice) aged 4 1/2 months, this study reveals significant differences in the seizure behavior of the two genotypes: whereas Syn1KO mice show both partial and generalized forebrain seizure activity, Syn2KO mice show only fully generalized forebrain seizures. Analysis of seizure behavior at earlier stages shows that the mature seizure pattern in Syn2KO mice establishes rapidly from the age of ∼2 months, when Syn1KO partial seizures are rare, and Syn1KO generalized seizures are almost absent. The specific behavioral phenotypes of the two strains suggest that the slight differences in structure, function and expression of these highly related proteins could be important factors during seizure generating neural activity.


Dipeptide synthesis by L-amino acid ligase from Ralstonia solanacearum.
Despite its utility, dipeptides have not been widely used due to the absence of an efficient manufacturing method. Recently, a novel method for effective production of dipeptides using l-amino acid alpha-ligase (Lal) is presented. Lal, which is only identified in Bacillus subtilis, catalyzes dipeptide synthesis from unprotected amino acids in an ATP-dependent manner. However, not all the dipeptide can be synthesized by Lal from B. subtilis (BsLal) due to its substrate specificity. Here, we attempted to find a novel Lal exhibiting different substrate specificity from BsLal. By in silico screening based on the amino acid sequence of BsLal, RSp1486a an unknown protein from Ralstonia solanacearum was found to show the Lal activity. RSp1486a exhibited different substrate specificity from BsLal, and preferably synthesized hetero-dipeptides where more bulky amino acid was placed at N terminus and less bulky amino acid was placed at C terminus in opposition to those synthesized by BsLal.


0957 + 561 A, B: twin quasistellar objects or gravitational lens?
0957 + 561 A, B are two QSOs of mag 17 with 5.7 arc s separation at redshift 1.405. Their spectra leave little doubt that they are associated. Difficulties arise in describing them as two distinct objects and the possibility that they are two images of the same object formed by a gravitational lens is discussed.


The neutralizing human recombinant antibodies to pathogenic Orthopoxviruses derived from a phage display immune library.
A panel of recombinant human antibodies to orthopoxviruses was isolated from a combinatorial phage display library of human scFv antibodies constructed from the Vh and Vl genes cloned from the peripheral blood lymphocytes of Vaccinia virus (VACV) immune donors. Plaque-reduction neutralization tests showed that seven selected phage-displaying scFv antibodies (pdAbs) neutralized both CPXV and VACV, and five of them neutralized Monkeypox virus (MPXV). Western blot analysis of VACV and CPXV proteins demonstrated that seven neutralizing antibodies recognized a 35 kDa protein. To identify this target protein, we produced a recombinant J3L protein of CPXV and showed that all the selected neutralizing antibodies recognized this protein. Neutralizing pdAb b9 was converted into fully human mAb b9 (fh b9), and scFv b9 displayed high binding affinities (K(d) of 0.7 and 3.2 nM). The fh b9 reduced VACV plaque formation in a dose-dependent manner.


Mid-career research training for the generalist physician: case study of a balancing act.
Although generalist physician faculty typically lack the skills needed to conduct research, few medical schools offer on-site faculty development programs that teach research skills. To address this dilemma, our medical school introduced a part-time Primary Care Research Fellowship offering full-day classes once a week over 10 months. We asked the 22 general internists, general pediatricians, and family physicians who participated in the program to rate their experience, and we measured their research productivity during the 3 years before and 3 years after completing the program, using a group of matched controls for comparison. Participants rated the program highly and increased their aggregate research productivity from 1 publication before completing the program to 6 publications afterward, although this increase did not reach statistical significance (p = .09). Controls exhibited substantially higher baseline productivity than fellows (10 publications vs. 1 publication, p = .03), but controls' productivity changed little between the first and second measurement periods (10 and 7 publications, respectively). Our mid-career research training program enabled primary care academic faculty to gain confidence in their ability to conduct a scientific study with minimal disruption to their teaching and clinical activities.


Identification of missense SNP-mediated mutations in the regulatory sites of aldose reductase (ALR2) responsible for treatment failure in diabetic complications.
Scientific pieces of evidence indicate that the polymorphism in the ALR2 regulatory gene favors the susceptibility to diabetic complications (DCs). Previous studies have uncovered several single nucleotide polymorphisms (SNPs) in the ALR2 regulatory sites that negatively modulate the activity of this enzyme and eventually increase the risks of DCs. In view of this, the current study aimed at investigating whether the mutation as a resultant of missense SNPs in the regulatory site of ALR2 enzyme can also hamper the interactions of ALR2 inhibitors with the key amino acid residues in the ALR2 binding site. Around 202 SNPs in the ALR2 gene were reported in the dbSNP database. Out of these, eighteen SNPs that are responsible for point mutations in the regulatory sites of ALR2 enzyme were identified and considered for the study. Identified SNPs were then categorized as stabilizing or destabilizing using various in silico tools and webservers. The resulting mutational constructs of ALR2 were further probed for their influence on the binding affinities and binding modes with well-known ALR2 inhibitors using structure-based analyses. This study identified three destabilizing SNPs, i.e., rs779176563 (C298S), rs1392886142 (G16A), and rs1407261115 (A245T), that lead to the compromised response to most of the ALR2 inhibitors which are in clinical trials. On the other hand, treatment with these ALR2 inhibitors may benefit the population which carries missense SNPs rs748119899, rs1402962430, and rs1467939858 that code for W219S, Q183V, and S214A, respectively. Overall findings of the study suggest that one SNP in the inhibitor site and two SNPs in the co-factor site of ALR2 may be responsible for the low efficacy and unsuccessful journey of ALR2 inhibitors in the clinical trials.


Impact of the gut microbiota on angiotensin Ⅱ-related disorders and its mechanisms.
The renin-angiotensin system (RAS) consists of multiple angiotensin peptides and performs various biological functions mediated by distinct receptors. Angiotensin II (Ang II) is the major effector of the RAS and affects the occurrence and development of inflammation, diabetes mellitus and its complications, hypertension, and end-organ damage via the Ang II type 1 receptor. Recently, considerable interest has been given to the association and interaction between the gut microbiota and host. Increasing evidence suggests that the gut microbiota may contribute to cardiovascular diseases, obesity, type 2 diabetes mellitus, chronic inflammatory diseases, and chronic kidney disease. Recent data have confirmed that Ang II can induce an imbalance in the intestinal flora and further aggravate disease progression. Furthermore, angiotensin converting enzyme 2 is another player in RAS, alleviates the deleterious effects of Ang II, modulates gut microbial dysbiosis, local and systemic immune responses associated with coronavirus disease 19. Due to the complicated etiology of pathologies, the precise mechanisms that link disease processes with specific characteristics of the gut microbiota remain obscure. This review aims to highlight the complex interactions between the gut microbiota and its metabolites in Ang II-related disease progression, and summarize the possible mechanisms. Deciphering these mechanisms will provide a theoretical basis for novel therapeutic strategies for disease prevention and treatment. Finally, we discuss therapies targeting the gut microbiota to treat Ang II-related disorders.


Gastrulation and Split Cord Malformation.
Split cord malformation (SCM) is a rare form of closed spinal dysraphism, in which two hemi-cords are present, instead of a single spinal cord. SCM is categorised into type 1 and type 2. Type 1 SCM is defined by the presence of a bony or osseocartilaginous spur between the hemi-cords, whereas type 2 SCM has no bony spur, and the two hemi-cords are contained within a single dura. In this chapter, we present the putative mechanisms by which SCM arises, including gastrulation defects and Pang's unified theory. The typical and rare clinical presentations and variations are described. Finally, we outline the step-by-step surgical approach to both SCM 1 and 2 and the overall prognosis of both conditions.


[Glomus tumors: anatomoclinical study of 14 cases with literature review].
Glomus tumor is a neuro-myo-arterial benign hamartoma. It is a relatively uncommon lesion. The aim of this study is to define all the unusual localizations of glomus tumor. From January 1999 to December 2006, we included in this retrospective study all patients who had the classic triad of symptoms with histological exam. We analysed epidemiological, clinical and therapeutical features of our patients. Fourteen patients were found to have histopathologically-proven glomus tumors. The patients, eight men and six women, had mean of age around 42 years. Three unusual locations were found: forearm, sacred region and parasternal. Most glomus tumors occur in the toes and fingertips. They are difficult to diagnose, despite painful symptom, because of their unusual locations. Glomus tumors are rare vascular tumors. The usual presentation is a solitary nodule in the distal portion of a digit, but can also occur wherever, with localizations unaccustomed and disconcerting.


Hypolipidemic and anti-inflammatory properties of Abacopterin A from Abacopteris penangiana in high-fat diet-induced hyperlipidemia mice.
This study was to investigate the hypolipidemic and anti-inflammatory properties of Abacopterin A (APA), a flavonoid compound isolated from Abacopteris penangiana (Hook.) Ching. Male C57BL/6J mice were divided randomly and equally into five groups: the normal control group (N), the model group (M), the positive control group (P), the high and low doses of APA treated groups (H and L). All the animals except that in N group were fed with high-fat diet for 8 weeks. In the last 4 weeks, the mice in P, H and L groups were orally administered with simvastatin (at the dose of 20mg/kg/day) and APA (at the dose of 40 or 20mg/kg/day), respectively. Then the lipid profiles and related biochemical criterions of the studied mice were determined. The effects of high-fat diet on activating nuclear transcription factor-κB (NFκB) expression, elevating inflammatory factors tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) levels, and increasing triacylglycerol (TG) and total cholesterol (TC) levels were abolished on daily supplementation with APA. APA also enhanced lipoprotein lipase (LPL) and hepatic lipase (HL) activities. These results suggested that APA had hypolipidemic and anti-inflammatory properties through inhibiting NFκB expression, and reducing inflammatory response.


The management of children born to human immunodeficiency virus seropositive women.
Increasing numbers of children born to human immunodeficiency virus (HIV) antibody-positive women are being identified, but guidelines as to their management are lacking. We have therefore established a paediatric counselling and screening clinic for managing such children in Edinburgh. During a period of 3 years, 49 infants and children of 43 HIV seropositive women have been seen. After a median follow-up period of 23 months, four children were found to have clinical evidence of HIV disease which was non-specific and could have been missed had they not been regularly monitored. Thus, close surveillance of infants born to seropositive women is important. Identifying a single clinic where this is done has allowed experience to accumulate on issues beyond the medical management of these infants as well as contributing to the clinical care of infants with symptoms. Based on this experience, we have developed guidelines for managing children born to HIV antibody-positive women.


Bladder shape impact on the accuracy of ultrasonic estimation of bladder volume.
Variations in bladder shape can lead to errors in ultrasonic estimation of the bladder volume. The purposes of this study were to compare the accuracies of various formulas to estimate bladder volume from sonographic measurements and to assess the impact of bladder shape on the accuracy of bladder volume estimation. Twenty-four healthy volunteers (13 men, 11 women) and 55 spinal cord injury patients (48 men, 7 women) underwent ultrasonographic measurements of dimensions before and after voiding. Bladder shape was classified as cuboid, ellipsoid, or triangular prism. Ten formulas from the literature were applied to estimate bladder volume, using the volume voided or catheterized as the standard, and then linear regression was used to obtain optimal correction coefficients for the whole data set as well as each of the three bladder shapes. Rehabilitation hospital affiliated with a medical college. The most accurate of the 10 formulas tested was height (H) X transverse depth (Dt) x weight (W) x 0.7 (mean error 17.4%+/-11.6%). Linear regression analysis yield optimal correction coefficients of .72 for the whole data set and .89, .81, and .66 for cuboidal, ellipsoid, and triangular prism-shaped bladders, respectively. The mean error for the estimation of bladder volume using .72 as the correction coefficient was 16.9%+/-11.9% and decreased to 12.7%+/-10.1% (p < .0001, paired t test) when the bladder shape was taken into account. Using bladder shape for reference and applying the corresponding correction coefficient to volume calculations will improve the accuracy of the estimation.


All-Solid-State Batteries with a Limited Lithium Metal Anode at Room Temperature using a Garnet-Based Electrolyte.
Metallic lithium (Li), considered as the ultimate anode, is expected to promise high-energy rechargeable batteries. However, owing to the continuous Li consumption during the repeated Li plating/stripping cycling, excess amount of the Li metal anode is commonly utilized in lithium-metal batteries (LMBs), leading to reduced energy density and increased cost. Here, an all-solid-state lithium-metal battery (ASSLMB) based on a garnet-oxide solid electrolyte with an ultralow negative/positive electrode capacity ratio (N/P ratio) is reported. Compared with the counterpart using a liquid electrolyte at the same low N/P ratios, ASSLMBs show longer cycling life, which is attributed to the higher Coulombic efficiency maintained during cycling. The effect of the species of the interface layer on the cycling performance of ASSLMBs with low N/P ratio is also studied. Importantly, it is demonstrated that the ASSLMB using a limited Li metal anode paired with a LiFePO4 cathode (5.9 N/P ratio) delivers a stable long-term cycling performance at room temperature. Furthermore, it is revealed that enhanced specific energies for ASSLMBs with low N/P ratios can be further achieved by the use of a high-voltage or high mass-loading cathode. This study sheds light on the practical high-energy all-solid-state batteries under the constrained condition of a limited Li metal anode.


Prevention is better than cure: Surgical methods for neuropathic pain prevention following amputation - A systematic review.
Pain after amputation can be known as residual limb pain (RLP) or phantom limb pain (PLP); however, both can be disabling in daily life with reported incidences of 8% for finger amputations and up to 85% for major limb amputations. The current treatment is focused on reducing the pain after neuropathic pain occurs. However, surgical techniques to prevent neuropathic pain after amputation are available and effective, but they are underutilized. The purpose of the review is to investigate the effects of techniques during amputation to prevent neuropathic pain. A systematic review was performed in multiple databases (Embase, Medline, Web of Science, Scopus, Cochrane, and Google Scholar) and following the PRISMA guidelines. Studies that reported surgical techniques to prevent neuropathic pain during limb amputation were included. Of the 6188 selected studies, 13 eligible articles were selected. Five articles reported techniques for finger amputation: neurovascular island flap, centro-central union (CCU), and epineural ligatures, and flaps. For finger amputations, the use of prevention techniques resulted in a decrease of incidences from 8% to 0-3% with CCU being the most beneficial. For major limb amputations, the incidences for RLP were decreased to 0 to 55% with TMR and RPNI and compared to 64-91% for the control group. Eight articles reported techniques for amputations on major limbs: targeted muscle reinnervation (TMR), targeted nerve implantation, concomitant nerve coaptation, and regenerative peripheral nerve interface (RPNI). Based on the current literature, we state that during finger and major limb amputation, the techniques to prevent neuropathic pain and PLP should be performed.


Noninfectious complications of acute stroke and their impact on hospital mortality in patients admitted to a stroke unit in Warsaw from 1995 to 2015.
Medical complications often worsen the prognosis after stroke. Our aim was to investigate the association between particular noninfectious complications and hospital mortality of acute stroke patients admitted to an urban Polish stroke center, and changes in their occurrence from 1995 to 2015. This is a retrospective analysis of 5174 consecutive patients admitted for acute ischemic stroke or cerebral hemorrhage to a Polish urban stroke center between 1995 and 2015. The occurrence of complications was reported for years 1995-2000 (n=883), 2001-2006 (n=1567), 2006-2010 (n=1539) and 2011-2015 (n=1183). Odds ratios (OR) with 95% confidence interval (95% CI) for stroke unit death were calculated after adjustment for age, congestive heart failure (CHF), pre-existing disability, stroke type and baseline neurological deficit in three different time periods. Over time there was a significant decrease in the occurrence of myocardial infarction (MI) (2.2%, 1.4%, 1.0% and 0.3%, respectively), exacerbated CHF (4.6%, 5.1%, 2.6% and 2.0%) and deep vein thrombosis (DVT) (4.6%, 2.7%, 1.2% and 1.1%). Adjusted odds for stroke unit death were increased by myocardial infarction (MI) (OR 17.5, 95% CI: 8.5-35.7), exacerbated CHF (OR 15.0, 95% CI: 9.8-23.0), pulmonary embolism (PE) (OR 11.5, 95% CI: 6.1-21.6), gastrointestinal bleeding (OR 9.2, 95% CI: 4.4-18.9) and recurrent stroke (OR 5.4, 95% CI: 3.1-9.3). Over the last two decades Polish urban stroke units may have achieved a significant reduction of the occurrence of some noninfectious complications (i.e. MI, exacerbated CHF and DVT). However, the list of conditions associated with stroke unit mortality includes not only MI and exacerbated CHF but also PE, gastrointestinal bleeding and recurrent stroke.


The first case of teeth discoloration induced by linezolid in children in China Mainland.
Linezolid is an oxazolidinone antimicrobial agent often used to treat multidrug-resistant Gram-positive bacterial infections. The common adverse reactions of linezolid are diarrhea, nausea, headache and bone marrow suppression, and so on. Here, we report the first case of teeth discoloration induced by linezolid linked with extrinsic discoloration in China Mainland. This case report highlights a rare adverse reactions of a commonly used antibiotic.


Long-term survival following traumatic brain injury.
The study used a retrospective cohort design to establish long-term mortality rates and predictors of mortality for persons after moderate to severe traumatic brain injury (TBI). Consecutive records of persons with moderate to severe TBI who were discharged from a large rehabilitation hospital in Pittsburgh, Pennsylvania in the years 1974-1984, 1988 and 1989 were reviewed. Six hundred and forty-two eligible individuals were identified and mortality was ascertained up to 24 years post injury. One hundred and twenty-eight of these individuals were found to be deceased. Poisson regression analyses revealed at least a 2-fold increased risk for mortality compared to the general population. Pre-injury characteristics and levels of disability at discharge from in-patient rehabilitation were among the strongest predictors of mortality. These data constitute evidence for premature death in the post-acute TBI population following a moderate to severe head injury and are discussed in relation to other research in the area.


Fate of pendimethalin in soil and characterization of non-extractable residues (NER).
One important route of degradation of herbicide pendimethalin in soil leads to formation of non-extractable residues (NER). To investigate NER nature (irreversibly, chemically bound, including possible biogenic NER, or strongly sorbed and entrapped) residues of 14C-labelled pendimethalin in soil were investigated after conventional extraction with organic solvents by silylation. After 400 days of incubation, 32.0% of applied radioactivity (AR) was transformed into NER, 39.9% AR remained extractable. Mineralization reached 26.2% AR. Additionally, 14C-pendimethalin was incubated in soil amended with compost for 217 days to investigate the influence of organic amendments on NER formation. NER amounted to 37.8% AR, with 57.9% AR remaining extractable. Mineralization was negligible (1.4% AR). For all sampling times only low amounts of radioactivity were entrapped (<5% AR) in soil without compost amendment. Pendimethalin was present only in trace amounts (ca. 0.4% AR), other released residues consisted of undefined fractions (sum ≈2% AR). In soil amended with compost, silylation overall resulted in release of higher amounts of radioactivity (19% AR). Addition of compost led to an increase in potential entrapment and sorption sites for pendimethalin, forming higher amounts of strongly sorbed, entrapped residues. Furthermore, potential release of non-extractable pendimethalin residues was investigated by incubation of solvent-extracted soil (without compost amendment) mixed with fresh soil for additional 3 months. NER were partly mineralized (7% AR) and 20% became extractable with organic solvents. However, no pendimethalin or any known metabolites were found. It can be concluded that no parent pendimethalin was found and NER of pendimethalin in soil are mainly formed by covalent binding to organic matrix with only low potential of remobilization under natural conditions.


Epistatic interactions between the high pathogenicity island and other iron uptake systems shape Escherichia coli extra-intestinal virulence.
The intrinsic virulence of extra-intestinal pathogenic Escherichia coli is associated with numerous chromosomal and/or plasmid-borne genes, encoding diverse functions such as adhesins, toxins, and iron capture systems. However, the respective contribution to virulence of those genes seems to depend on the genetic background and is poorly understood. Here, we analyze genomes of 232 strains of sequence type complex STc58 and show that virulence (quantified in a mouse model of sepsis) emerged in a sub-group of STc58 due to the presence of the siderophore-encoding high-pathogenicity island (HPI). When extending our genome-wide association study to 370 Escherichia strains, we show that full virulence is associated with the presence of the aer or sit operons, in addition to the HPI. The prevalence of these operons, their co-occurrence and their genomic location depend on strain phylogeny. Thus, selection of lineage-dependent specific associations of virulence-associated genes argues for strong epistatic interactions shaping the emergence of virulence in E. coli.


Seed dispersal by nutcrackers causes multi-trunk growth form in pines.
We present a unique example of a seed disperser determining the basic growth architecture of two species of plants. Clark's Nutcracker (Nucifraga columbiana) is the primary disperser for Pinus flexilis and P. albicaulis, caching clusters of seeds in the process. Both pine species often occur in a multi-trunk growth form at maturity. Electrophoretic analysis based on 2 to 4 gene loci revealed that two or more trunks were genetically distinct individuals in twenty of the twenty-five multi-trunk trees sampled. This supports the hypothesis that several mature individuals can arise from single caches.


The effect of inter-pregnancy interval on stillbirth in urban South Ethiopia: a community-based prospective cohort study.
Stillbirth is an invisible and poorly understood adverse pregnancy outcome that remains a challenge in clinical practice in low-resource settings. It is also a key concern in Ethiopia where more than half of pregnancies occur shortly after preceding childbirth. Whether the interval between pregnancies has an effect on stillbirth or not is unclear. Therefore, we aimed to assess the effect of inter-pregnancy interval on stillbirth in urban South Ethiopia. A community-based prospective cohort study was conducted among 2578 pregnant women and followed until delivery. Baseline data were collected at the household level during registration and enrolment. End-line data were collected from hospitals during delivery. Exposed groups were pregnant women with inter-pregnancy intervals < 18 months and 18-23 months. Unexposed group contains women with inter-pregnancy intervals 24-60 months. A generalized linear model for binary outcome was applied, using R version 4.0.5 software. Relative risk (RR) was used to estimate the effect size with a 95% confidence level. Attributable fraction (AF) and population attributable fraction (PAF) were used to report the public health impact of exposure. The overall incidence of stillbirth was 15 per 1000 total births, (95% CI: 11, 20%). However, the incidence was varied across months of inter-pregnancy intervals; 30 (< 18 months), 8 (18-23 months) and 10 (24-60 months) per 1000 total births. The risk of stillbirth was nearly four times (ARR = 3.55, 95%CI: 1.64, 7.68) higher for women with inter-pregnancy interval < 18 months as compared to 24-60 months. This means, about 72% (AF = 72, 95%CI: 39, 87%) of stillbirth among the exposed group (inter-pregnancy interval < 18 months category) and 42% (PAF = 42, 95%CI: 23, 50%) of stillbirth in the study population were attributed to inter-pregnancy interval < 18 months. These could be prevented with an inter-pregnancy interval that is at least 18 months or longer. Inter-pregnancy interval under 18 months increases the risk of stillbirth in this population in urban South Ethiopia. Interventions targeting factors contributing to short inter-pregnancy intervals could help in reducing the risk of stillbirth. Improving contraceptive utilization in the community could be one of these interventions.


Systematic investigation of imprinted gene expression and enrichment in the mouse brain explored at single-cell resolution.
Although a number of imprinted genes are known to be highly expressed in the brain, and in certain brain regions in particular, whether they are truly over-represented in the brain has never been formally tested. Using thirteen single-cell RNA sequencing datasets we systematically investigated imprinted gene over-representation at the organ, brain region, and cell-specific levels. We established that imprinted genes are indeed over-represented in the adult brain, and in neurons particularly compared to other brain cell-types. We then examined brain-wide datasets to test enrichment within distinct brain regions and neuron subpopulations and demonstrated over-representation of imprinted genes in the hypothalamus, ventral midbrain, pons and medulla. Finally, using datasets focusing on these regions of enrichment, we identified hypothalamic neuroendocrine populations and the monoaminergic hindbrain neurons as specific hotspots of imprinted gene expression. These analyses provide the first robust assessment of the neural systems on which imprinted genes converge. Moreover, the unbiased approach, with each analysis informed by the findings of the previous level, permits highly informed inferences about the functions on which imprinted gene expression converges. Our findings indicate the neuronal regulation of motivated behaviours such as feeding and sleep, alongside the regulation of pituitary function, as functional hotspots for imprinting. This adds statistical rigour to prior assumptions and provides testable predictions for novel neural and behavioural phenotypes associated with specific genes and imprinted gene networks. In turn, this work sheds further light on the potential evolutionary drivers of genomic imprinting in the brain.


Dysregulation of GIMAP genes in non-small cell lung cancer.
The GIMAP (GTPase of the immunity-associated protein) gene family includes seven functional members residing on human chromosome 7. GIMAP genes encode GTP-binding proteins that share a unique primary structure and whose function is largely unknown. However, gene ablation studies reveal that Gimap4 plays an important role in regulating the apoptosis of T cells. In a pilot microarray analysis on six cases of non-small cell lung cancer (NSCLC), we discovered that the expression of GIMAP family members, but not the neighboring non-GIMAP genes, was uniformly lower in the tumor tissues, compared to that in the adjacent nontumor tissues. This finding was subsequently confirmed by quantitative PCR assays in a total of twenty NSCLCs, and we found that GIMAP6 and GIMAP8 showed striking reduction of gene expression in the tumors. In contrast, GIMAP8 mRNA level was abnormally elevated in the adjacent nontumor tissues as compared to that in the control lung tissues. Such reciprocal expression of GIMAPs suggests that this unique gene family might contribute to the pathogenesis of and immune reactions to NSCLC.


Evidence for causal effects of polycystic ovary syndrome on oxidative stress: a two-sample mendelian randomisation study.
Polycystic ovary syndrome (PCOS) is often accompanied by increased oxidative stress levels; however, it is still unclear whether PCOS itself is causally related to oxidative stress (OS), whether OS can increase the occurrence of PCOS, and which characteristics of PCOS increase OS levels. Therefore, this study explored the causal relationship between PCOS, its characteristics, and OS. Two-sample bidirectional and two-sample Mendelian randomisation studies were performed based on publicly available statistics from genome-wide association studies. PCOS; its characteristics, such as testosterone, low-density lipoprotein, high-density lipoprotein; and 11 major OS markers (superoxide dismutase, glutathione S-transferase, glutathione peroxidase, catalase, uric acid, zinc, tocopherol, ascorbic acid, retinol, albumin, and total bilirubin), were studied. The main analytical method used was inverse variance weighting (IVW). Pleiotropy was evaluated using the Mendelian randomisation-Egger intercept. Q and P values were used to assess heterogeneity. There was no causal relationship between PCOS and the OS indices (all P > 0.05). There was a causal relationship between the OS index, ascorbate level, and PCOS (IVW, odds ratio: 2.112, 95% confidence interval: 1.257-3.549, P = 0.005). In addition, there was a causal relationship between testosterone, low-density lipoprotein, high-density lipoprotein, sex hormone-binding globulin, body mass index, triacylglycerol, age at menarche, and most OS indices according to the IVW method. The F statistics showed that there was no weak instrumental variable. A sensitivity analysis was performed using the leave-one-out method. No pleiotropy was observed. The results were robust, and the conclusions were reliable. This study showed for the first time that there was no causal relationship between PCOS and OS. However, there was a causal relationship between the OS index, ascorbate level, and PCOS. It revealed that PCOS itself could not increase OS, and the increase in OS in PCOS was related to other potential factors, such as testosterone, low-density lipoprotein, high-density lipoprotein, sex hormone-binding globulin, body mass index, triacylglycerol, and age at menarche.


Rapid initial cleavage of nascent pre-rRNA transcripts in yeast.
In yeast cells, as in many other eukaryotes, the initial step in the processing of the pre-rRNA primary transcript is removal of external transcribed spacer (ETS) sequences from the 5' end of the transcript. We show here, both by Northern analysis and by quantitative hybridization procedures using cloned yeast ETS sequences, that in cells growing exponentially at 23 degrees C most nascent pre-rRNA transcripts no longer contain ETS sequences. Moreover, quantitative hybridization shows that uncleaved pre-rRNA molecules that still contain ETS sequences have a half-life of only 0.5 minute, a value that supports the finding that ETS removal usually takes place before pre-rRNA transcription is complete. Under these same conditions, the half-life of ETS sequences is shown to be only 1.0 minute.


Silica nanoparticles induce pulmonary autophagy dysfunction and epithelial-to-mesenchymal transition via p62/NF-κB signaling pathway.
It has been reported that silica nanoparticles (SiNPs) could cause epithelial-to-mesenchymal transition (EMT), but the specific mechanism is still unclear. Thus, the purpose of this study was to investigate the underlying mechanisms of pulmonary EMT after subacute exposure to SiNPs. The results showed intratracheal instillation of SiNPs increased the pulmonary MDA content, while decreased the activity of SOD and GSH-Px in rats. Western blot analysis demonstrated that SiNPs induced autophagy dysfunction via the upregulation of p62. Meanwhile, the inflammation cytokines (TNF-α, IL-18, IL-1β) were released in rat lung. Immunohistochemistry and western blot assays both showed that SiNPs could regulate the related protein biomarkers of EMT through decreasing E-cadherin and increasing vimentin in a dose-dependent manner. Besides, SiNPs activated the proteins expression involved in p62/NF-κB signaling pathway, whereas the pulmonary EMT induced by SiNPs was significantly dampened after the knock down of p62. In this study, we illustrated that subacute exposure to SiNPs could trigger the autophagy dysfunction and pulmonary inflammation, further lead to EMT via activating the p62/NF-κB signaling pathway. Our findings provide new molecular evidence for SiNPs-induced pulmonary toxicity.


Removal and recovery of copper (II) ions by bacterial biosorption.
Studies were conducted to investigate the removal and recovery of copper (II) ions from aqueous solutions by Micrococcus sp., which was isolated from a local activated sludge process. The equilibrium of copper biosorption followed the Langmuir isotherm model very well with a maximum biosorption capacity (q(max)) of 36.5 mg of Cu2+/g of dry cell at pH 5.0 and 52.1 mg of Cu2+/g of dry cell at pH 6.0. Cells harvested at exponential growth phase and stationary phase showed similar biosorption characteristics for copper. Copper uptake by cells was negligible at pH 2.0 and then increased rapidly with increasing pH until 6.0. In multimetal systems, Micrococcus sp. exhibited a preferential biosorption order: Cu approximate to Pb > Ni approximate to Zn. There is virtually no interference with copper uptake by Micrococcus sp. from solutions bearing high concentrations of Cl-, SO4(2-), and NO3- (0-500 mg/L). Sulfuric acid (0.05 M) was the most efficient desorption medium, recovering >90% of the initial copper sorbed. The copper capacity of Micrococcus sp. remained unchanged after five successive sorption and desorption cycles. Immobilization of Micrococcus sp. in 2% calcium alginate and 10% polyacrylamide gel beads increased copper uptake by 61%. Biomass of Micrococcus sp. may be applicable to the development of potentially cost-effective biosorbent for removing and recovering copper from effluents.


Effect of Probiotics Supplementation on Heart Rate: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.
Probiotics consumption lowers the risk of cardiovascular disease, but whether it affects heart rate (HR) remains controversial. Therefore, our study aimed to assess the chronotropic effects of probiotics on heartbeat via a meta-analysis of randomized clinical trials. Relevant studies were identified by searching PubMed, Cochrane library, and Clinical Trials databases up to October 2021. Either a fixed-effects or a random-effects model was used to calculate the pooled effect sizes and 95% confidence intervals (CIs). This meta-analysis included 13 studies involving 16 interventional trial arms and 931 participants according to inclusion criteria. The overall pooled estimate showed that probiotics supplementation had a slight, but no significant reduction of 0.28 bpm (95% CI: -1.17, 0.60) on HR. Relatively high heterogeneity was observed among included trials (I 2 = 80.8%, P heterogeneity < 0.001). Subgroup analysis displayed that probiotics supplementation significantly reduced HR by 2.94 bpm (95% CI: -5.06, -0.82) among participants with baseline HR ≥ 75 bpm, by 1.17 bpm (95% CI: -2.34, -0.00) with probiotics dose ≥1 × 1010 CFU/day, and by 1.43 bpm (95% CI: -2.69, -0.17) with multiple-strain intervention. Meta-regression analysis showed that baseline HR was a major potential effect modifier of probiotics supplementation on lowering HR. Hitherto, the overall evidence in the literature was insufficient to support the notion that probiotics supplementation has a class effect on HR reduction. However, in subgroup analysis, probiotics reduced HR significantly in those who had higher baseline HR, received a higher dose or multiple strains of probiotics.


Hospital markets in the United States, 2007-2017.
U.S. hospital markets have undergone consolidation in recent decades with the growth of large "health systems," but little is known about the characteristics of systems, and whether certain geographic areas or service types (e.g. intensive care, obstetrics) have been differentially impacted by consolidation. Using 2007-2017 American Hospital Association data, we characterized health systems and their growth, and determined how changes in hospital market structure have differentially affected specific service types and geographic areas. Despite a national trend of reduced hospital utilization, health systems grew larger during our study period. Hospital markets were already highly concentrated in 2007 and became even more concentrated between 2007 and 2017, across all service types that we measured. The least concentrated service was emergency department care, while intensive care and obstetrics were the most concentrated. As of 2017, 19.0% of markets - representing 11.2 million Americans - are served by only one hospital system. Concentrated markets are less populous, poorer areas and have lower physician supply than less concentrated markets. Hospital markets were highly concentrated in 2007 and have since become more concentrated in the subsequent decade. Hospital consolidation is a nationwide phenomenon, and is occurring across hospital service types. Antitrust alone may be insufficient to address high and increasing hospital market power. Decreasing barriers to entry may allow for more competition.


Interaction among health workers and trans men: Findings from a qualitative study in Chile.
To explore trans men's access and use of healthcare services in Chile, based on the experiences of the trans men themselves, as well as of healthcare professionals. A qualitative study with an ethnographic approach was carried out with 30 participants: 14 trans men and 16 healthcare professionals. Semi-structured one-on-one interviews with open-ended questions were used to collect the data. A thematic analysis was carried out with the NVivo Software. Three main themes were identified: (1) failures in the recognition of trans identity, (2) challenges with patient-centered care, and (3) use of other ("non-trans") health services. The results suggest that not all transition processes are the same, individuals seek different ways; therefore, it is necessary to consider different body types and identities when planning programs and care for men in transition. Moreover, the accompaniment provided during the gender transition process should contemplate emotional and mental support. The study outlines the need for all healthcare professionals to have training and knowledge about the transgender population, regardless of whether they are part of the teams supporting gender transition processes. The role of nurses and the contributions that can be made from nursing discipline in this research field are fundamental.


Association of frailty with outcomes of resection for colonic volvulus: A national analysis.
With limited national studies available, we characterized the association of frailty with outcomes of surgical resection for colonic volvulus. Adults with sigmoid or cecal volvulus undergoing non-elective colectomy were identified in the 2010-2019 Nationwide Readmissions Database. Frailty was identified using the Johns Hopkins indicator which utilizes administrative codes. Multivariable models were developed to examine the association of frailty with in-hospital mortality, perioperative complications, stoma use, length of stay, hospitalization costs, non-home discharge, and 30-day non-elective readmissions. An estimated 66,767 patients underwent resection for colonic volvulus (Sigmoid: 39.6%; Cecal: 60.4%). Using the Johns Hopkins indicator, 30.3% of patients with sigmoid volvulus and 15.9% of those with cecal volvulus were considered frail. After adjustment, frail patients had higher risk of mortality compared to non-frail in both sigmoid (10.6% [95% CI 9.47-11.7] vs 5.7% [95% CI 5.2-6.2]) and cecal (10.4% [95% CI 9.2-11.6] vs 3.5% [95% CI 3.2-3.8]) volvulus cohorts. Frailty was associated with greater odds of acute venous thromboembolism occurrences (Sigmoid: AOR 1.50 [95% CI 1.18-1.94]; Cecal: AOR 2.0 [95% CI 1.50-2.72]), colostomy formation (Sigmoid: AOR 1.73 [95% CI 1.57-1.91]; Cecal: AOR 1.48 [95% CI 1.10-2.00]), non-home discharge (Sigmoid: AOR 1.97 [95% CI 1.77-2.20]; Cecal: AOR 2.56 [95% CI 2.27-2.89]), and 30-day readmission (Sigmoid: AOR 1.15 [95% CI 1.01-1.30]; Cecal: AOR 1.26 [95% CI 1.10-1.45]). Frailty was associated with incremental increase in length of stay (Sigmoid: +3.4 days [95% CI 2.8-3.9]; Cecal: +3.8 days [95% CI 3.3-4.4]) and costs (Sigmoid: +$7.5k [95% CI 5.9-9.1]; Cecal: +$12.1k [95% CI 10.1-14.1]). Frailty, measured using a simplified administrative tool, is associated with significantly worse clinical and financial outcomes following non-elective resections for colonic volvulus. Standard assessment of frailty may aid risk-stratification, better inform shared-decision making, and guide healthcare teams in targeted resource allocation in this vulnerable patient population.


The effectiveness of peer support on self-efficacy and self-management in people with type 2 diabetes: A meta-analysis.
This study aims to investigate the effectiveness of peer support on self-efficacy and self-management in people with type 2 diabetes. Eight databases were utilized for selecting eligible studies that were published from inception to Jan., 2020. The eligible studies were screened, extracted and then the methodological quality was evaluated independently by two researchers. RevMan version 5.3 software and Stata version 14.0 software were utilized for the meta-analysis. Seventeen studies were included in the meta-analysis. Compared with the control group, peer support significantly improved self-efficacy [SMD = 0.41, 95 % CI = (0.20, 0.62), p = 0.0001] and self-management [SMD = 1.21, 95 % CI = (0.58, 1.84), p = 0.0002] in people with type 2 diabetes, but had no significant effect on distress (p = 0.34). Peer support significantly improved self-efficacy and self-management, but there was no clear evidence that peer support improved distress in people with type 2 diabetes. More studies are needed to further verify the validity of the results. This meta-analysis suggested that peer support should be considered as a complementary treatment for patients with type 2 diabetes. Medical staff can encourage the use of peer support in the teaching content of patients with type 2 diabetes to improve their self-efficacy and self-management.


Trends in Manufacturer-Reported Nicotine Yields in Cigarettes Sold in the United States, 2013-2016.
A gradual reduction of cigarette nicotine content to nonaddictive levels has been proposed as an endgame strategy to accelerate declines in combustible tobacco smoking. We assessed manufacturer-reported nicotine yield in cigarettes sold in the United States from 2013 to 2016. We merged machine-measured nicotine yield in cigarette smoke and pack characteristics obtained from reports filed by tobacco manufacturers with the Federal Trade Commission for 2013-2016 with monthly Nielsen data on US cigarette sales. Manufacturer-reported, sales-weighted, average annual nicotine yield was assessed, as were nicotine yield sales trends by quartile: markedly low (0.10-0.60 mg/stick), low (0.61-0.80 mg/stick), moderate (0.81-0.90 mg/stick), and high (0.91-3.00 mg/stick). Trends in overall, menthol, and nonmenthol pack sales, by nicotine yield quartiles over the study period and by year, were determined by using Joinpoint regression. During 2013-2016, average annual sales-weighted nicotine yield for all cigarettes increased from 0.903 mg/stick (95% CI, 0.882-0.925) in 2013 to 0.938 mg/stick (95% CI, 0.915-0.962) in 2016 (P < .05). For menthol cigarettes, yield increased from 0.943 mg/stick in 2013 (95% CI, 0.909-0.977) to 1.037 mg/stick in 2016 (95% CI, 0.993-1.081), increasing 0.2% each month (P < .05). Most pack sales occurred among high (41.5%) and low (30.7%) nicotine yield quartiles. Cigarette sales for the markedly low quartile decreased by an average of 0.4% each month during 2013-2016 (P < .05). During 2013-2016, manufacturer-reported, sales-weighted nicotine yield in cigarettes increased, most notably for menthol cigarettes. Continued monitoring of nicotine yield and content in cigarettes can inform tobacco control strategies.


Methylome-wide association study of anxiety disorders.
Anxiety Disorders (ANX) such as panic disorder, generalized anxiety disorder, and phobias, are highly prevalent conditions that are moderately heritable. Evidence suggests that DNA methylation may play a role, as it is involved in critical adaptations to changing environments. Applying an enrichment-based sequencing approach covering nearly 28 million autosomal CpG sites, we conducted a methylome-wide association study (MWAS) of lifetime ANX in 1132 participants (618 cases/514 controls) from the Netherlands Study of Depression and Anxiety. Using epigenomic deconvolution, we performed MWAS for the main cell types in blood: granulocytes, T-cells, B-cells and monocytes. Cell-type specific analyses identified 280 and 82 methylome-wide significant associations (q-value < 0.1) in monocytes and granulocytes, respectively. Our top finding in monocytes was located in ZNF823 on chromosome 19 (p = 1.38 × 10-10) previously associated with schizophrenia. We observed significant overlap (p < 1 × 10-06) with the same direction of effect in monocytes (210 sites), T-cells (135 sites), and B-cells (727 sites) between this Discovery MWAS signal and a comparable replication dataset from the Great Smoky Mountains Study (N = 433). Overlapping Discovery-Replication MWAS signal was enriched for findings from published GWAS of ANX, major depression, and post-traumatic stress disorder. In monocytes, two specific sites in the FZR1 gene showed significant replication after Bonferroni correction with an additional 15 nominally replicated sites in monocytes and 4 in T-cells. FZR1 regulates neurogenesis in the hippocampus, and its knockout leads to impairments in associative fear memory and long-term potentiation in mice. In the largest and most extensive methylome-wide study of ANX, we identified replicable methylation sites located in genes of potential relevance for brain mechanisms of psychiatric conditions.


Environmental implication and cancer risk assessment of residual pollutants in cotton crop: a case study of Multan District, Pakistan.
Pakistan is the fourth largest yarn producer in the world heavily that relies on cotton crop which receives a substantial 62% of all pesticide applications. The present study was conducted to quantify the levels of pesticides such as bifenthrin, spirotetramat, pyriproxyfen, imidacloprid, and diafenthiuron in soil and plants residue at selected cotton fields of Multan District, Pakistan. In addition to pesticides, the assessment of heavy metal concentration was also conducted in order to determine the overall risks that these compounds to both plants and human population. For this analysis, 20 soil samples and 10 plant samples were collected from 10 selected cotton fields. Pesticides and heavy metals in soil and plant samples were analyzed using high-performance liquid chromatography (HPLC) and Inductively Coupled Plasma-Optical Emission Spectroscopy (ICP-OES), respectively. It was observed that all samples collected from selected fields contained pesticide residue in top soil (0-15 cm). However, no pesticides were detected in the lower soil layer (16-30 cm). In case of heavy metals, the highest concentration of Fe, Pb, and Mn was observed in both soil and plant residue samples. The heavy metals were found in the order of Fe > Mn > Pb > Zn > Cu > Cd in the soil. The total carcinogenic risk values for a few pesticides were found to range from 10-6 to 10-2, indicating that residents of the study area have low to higher chances of developing cancer. A positive correlation was observed among the pesticides (r = 0.18-0.95) as well as in metals related parameters (r = 0.49-0.96), where a weak negative correlation was found among metal to pesticide parameters except Pd where the maximum r value was 0.62. In general, the finding of this study encourages the development and adoption of sustainable agricultural practices that lower the dependence on toxic pesticides and endorse environmentally friendly alternatives.


National Cancer Institute Collaborative Workshop on Shaping the Landscape of Brain Metastases Research: challenges and recommended priorities.
Brain metastases are an increasing global public health concern, even as survival rates improve for patients with metastatic disease. Both metastases and the sequelae of their treatment are key determinants of the inter-related priorities of patient survival, function, and quality of life, mandating a multidimensional approach to clinical care and research. At a virtual National Cancer Institute Workshop in September, 2022, key stakeholders convened to define research priorities to address the crucial areas of unmet need for patients with brain metastases to achieve meaningful advances in patient outcomes. This Policy Review outlines existing knowledge gaps, collaborative opportunities, and specific recommendations regarding consensus priorities and future directions in brain metastases research. Achieving major advances in research will require enhanced coordination between the ongoing efforts of individual organisations and consortia. Importantly, the continual and active engagement of patients and patient advocates will be necessary to ensure that the directionality of all efforts reflects what is most meaningful in the context of patient care.


Histomorphometric bone modifications induced by growth hormone treatment in a rabbit model of short bowel syndrome.
The effects of recombinant human growth hormone (rhGH) on cancellous and cortical bone were investigated in an experimental rabbit model of short bowel syndrome (SBS). Eighteen young male New Zealand rabbits, 2.0 +/- 0.2 kg b.w., were divided into three groups: an SBS Group submitted to a 70% midjejunoileal enterectomy and reanastomosis; an SBS-GH Group undergoing the same surgery and receiving 0.4 mg/kg/day rhGH for 28 days; a Control Group which was sham-operated. Thirty-five days after surgery, all the animals were pharmacologically euthanised and their femurs and L5 vertebrae were used for densitometric and histomorphometric studies. Vertebral and femoral densitometric results showed that the SBS Group presented significantly (P<0.01) lower values (10-25%) than the Control and SBS-GH Groups. Significant differences in the cancellous histomorphometric parameters, namely the trabecular bone area (-7% to 46%), trabecular thickness (-21% to 34%) and trabecular separation (17-32%), were observed between the SBS Group and the other groups. Both the SBS and SBS-GH Groups showed significantly (P<0.05) higher values than the Control Group in terms of cross-sectional area (approximately 24%), cortical area (approximately 20%), and periosteal perimeter (approximately 9%), while medullary area (41%) and endocortical perimeter (18%) were significantly higher (P<0.05) in SBS Group than those of Control Group. The current findings are encouraging and suggest that GH administration in SBS animal model used may improve skeletal tissue remodelling.


Transcription and activation under environmental stress of the complex telomeric repeats of Chironomus thummi.
In contrast to their traditional role, telomeres seem to behave as transcriptionally active regions. RNAs complementary to the short DNA repeats characteristic of telomerase-maintained telomeres have recently been identified in various mammalian cell lines, representing a new and unexpected element in telomere architecture. Here, we report the existence of transcripts complementary to telomeric sequences characteristic of Chironomus thummi telomeres. As in other Diptera, the non-canonical telomeres of chironomids lack the simple telomerase repeats and have instead more complex repetitive sequences. Northern blots of total RNA hybridized with telomere probes and RT-PCR with telomere-specific tailed primers confirm the existence of small non-coding RNAs of around 200 bp, the size of the DNA repeated telomeric unit. Telomere transcripts are heterogeneous in length, and they appear as a ladder pattern that probably corresponds to multimers of the repeat. Moreover, telomeres are activated under conditions of environmental stress, such as heat shock, appearing highly decondensed and densely labelled with acetylated H4 histone, as well as with RNA polymerase II antibodies, both marks of transcriptional activity. Changes in the expression levels of telomeric RNA were detected after heat shock. These findings provide evidence that transcriptional activity of the repetitive telomere sequences is an evolutionarily conserved feature, not limited to telomerase telomeres. The functional significance of this non-coding RNA as a new additional element in the context of telomere biology remains to be explained.


The effect of various doses of oral oestradiolvalerate and oestriolsuccinate on urine calcium/creatinine, serum FSH and endometrium in castrated women.
The effects of various doses recommended for clinical use of oestradiolvalerate and oestriolsuccinate on urine calcium/creatinine, serum FSH and endometrium were investigated in two castrated women. Oestrogen treatments were given in 6-week periods separated by 2 weeks without treatment. After various oestrogen treatments, serum FSH generally decreased clearly and urine calcium/creatinine slightly. The proliferative effect on endometrium was investigated histologically. In no period was a hyperplastic endometrium found.


X-ray diffraction studies of lipid phase transitions in hydrated mixtures of cholesterol and diacylphosphatidylcholines and their relevance to the structure of biological membranes.
Previous X-ray diffraction data on the effects of temperature on hydrated cholesterol/dimyristoylphosphatidylcholine mixtures have been confirmed and equivalent new data on cholesterol/stearolyoleoylphosphatidylcholine obtained. Molecular interpretations are discussed and related to previous studies of cholesterol/dioleoylphosphatidylcholine and of cholesterol-rich biological membranes.


Survivorship analysis of cemented total condylar knee arthroplasty.
From 1977 to 1989, the authors performed and prospectively followed 151 cemented total condylar knee arthroplasties in 113 patients. A metal-backed tibial component was implanted in 133 knees (88%). The mean followup of all knees was 7 years (range, 0.5-16 years); 36 knees were seen in followup for a minimum of 10 years. Survivorship analysis was used to calculate the predicted cumulative rate of success of these knees. Using the criteria for failure as revision performed or recommended, the 10-year survival of these knees was 96.9% (95% confidence interval, 93.8%-100%). Including those knees with radiographic loosening, the 10-year survival was 84.1% (95% confidence interval, 73.4%-96.3%). The cemented total condylar prosthesis remains the standard for success and durability of total knee arthroplasties.


The kinase complex mTORC2 promotes the longevity of virus-specific memory CD4+ T cells by preventing ferroptosis.
Antigen-specific memory CD4+ T cells can persist and confer rapid and efficient protection from microbial reinfection. However, the mechanisms underlying the long-term maintenance of the memory CD4+ T cell pool remain largely unknown. Here, using a mouse model of acute infection with lymphocytic choriomeningitis virus (LCMV), we found that the serine/threonine kinase complex mammalian target of rapamycin complex 2 (mTORC2) is critical for the long-term persistence of virus-specific memory CD4+ T cells. The perturbation of mTORC2 signaling at memory phase led to an enormous loss of virus-specific memory CD4+ T cells by a unique form of regulated cell death (RCD), ferroptosis. Mechanistically, mTORC2 inactivation resulted in the impaired phosphorylation of downstream AKT and GSK3β kinases, which induced aberrant mitochondrial reactive oxygen species (ROS) accumulation and ensuing ferroptosis-causative lipid peroxidation in virus-specific memory CD4+ T cells; furthermore, the disruption of this signaling cascade also inhibited glutathione peroxidase 4 (GPX4), a major scavenger of lipid peroxidation. Thus, the mTORC2-AKT-GSK3β axis functions as a key signaling hub to promote the longevity of virus-specific memory CD4+ T cells by preventing ferroptosis.


Patient Perspectives about Mild Cognitive Impairment: A Systematic Review.
Mild cognitive impairment (MCI) is a concept that is steeped in controversy not limited to prognostic uncertainty; it is unclear how patients interpret or attribute meaning to the label, and whether they perceive that being made aware is beneficial. A systematic review was conducted, searching ISI Web of Science, PubMed and PsycINFO in accordance with PRISMA guidelines. Search terms were developed to include articles concerning perceptions regarding MCI and experiences and impact of being informed. Thematic synthesis was applied to the findings. Fourteen papers met criteria. Three themes emerged regarding the MCI label: 1) Individual differences relating to living circumstances, personal perceptions and experiences, and coping style affect how patients adjust to the MCI label; 2) Patients' reactions to the MCI label and their perceptions about how useful it was to receive are affected by the nebulous nature of the construct and information available regarding MCI; 3) Care partners are uncertain about what MCI means and how to address and cope with the patient's cognitive difficulties. Patient and care partner perspectives were affected by the quality of information and support provided, possibly influenced by clinicians' understanding of the concept. Personal perceptions and experiences, living circumstance and coping styles also shaped experiences of being informed. Clinicians should develop their understanding of MCI to deliver clear information to patients and consider the necessity of applying the label. Offering support tailored to patients' specific needs may improve perceptions about the label's utility, whilst aiding coping and adjustment.


Primary angle-closure glaucoma among Alaskan Eskimos.
An epidemiological study of the occurrence of angle-closure glaucoma was made under the Eskimos population of the Norton Sound and Bering Straits region of Alaska. Among 1673 Alaskan Natives examined 14 cases (0.8%) of angle-closure glaucoma were found, in 0.5% of the men and 1.2% of the women; for persons above the age of 40 years these figures were 2.1% and 5.5% respectively. Angle-closure glaucoma was found in 11.8% of women above the age of 60 years. A shallow anterior chamber was seen twice as frequently in women as in men. Above the age of 30 years the chamber angle was considered to be occludable in 2% of men and 7.5% of women on gonioscopic examination. The average intra-ocular pressure of the right eyes of men was 11.7 mm Hg (s.d. 3.3) and of women 12.0 mm Hg (s.d. 3.4). Primary open-angle glaucoma was not seen in the population being studied.


Affinity purification of angiotensin type 2 receptors from N1E-115 cells: evidence for agonist-induced formation of multimeric complexes.
The murine neuroblastoma N1E-115 cell line possesses type 1 and type 2 angiotensin II (AngII) receptor subtypes. In vitro differentiation of these cells substantially increases the density of the AT2-receptor subtype, whereas the density of the AT1 receptors remains unchanged. In the present study, we report that the zwitterionic detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) selectively solubilized AT2 receptors from N1E-115 cell membranes and that these receptors could be purified further to near homogeneity by affinity chromatography. More specifically, the presence of an agonist (AngII) during affinity purification of AT2 receptors resulted in the elution of high (110-kDa) and low (66-kDa) molecular mass proteins as determined by gel electrophoresis under nonreducing conditions. In contrast, when the nonselective antagonist Sar1,Ile8-AngII was used during purification, only the lower 66-kDa protein was observed. Affinity purification in the presence of the peptide and nonpeptide AT2-receptor antagonists CGP42112A and PD123319 also resulted in elution of the same 66-kDa protein, but unlike that in the presence of Sar1,Ile8-AngII, some of the high molecular weight site was observed as well. On the other hand, Losartan, an AT1-receptor antagonist, was completely ineffective in eluting any AngII receptors from the affinity column, further confirming their AT2 identity. After agonist elution, the 110-kDa band dissociated into two low molecular mass bands of 66 kDa and 54 kDa when sodium dodecyl sulfate-gel electrophoresis was run under reducing conditions.(ABSTRACT TRUNCATED AT 250 WORDS)


Heat effects on seeds and rhizomes of a selection of boreal forest plants and potential reaction to fire.
To analyse the potential reaction to firegenerated heat pulses, seeds of 12 species of plants and rhizomes of three species were exposed to elevated temperatures for 10 min. The tested material split into three groups with respect to heat tolerance: (1) the rhizomes, for which the lethal temperatures were in the range 55-59° C; (2) the seeds of most of the species tested, for which the lethal temperatures were in the range 65-75° C; (3) The seeds of two species of Leguminosae and three species of Geranium for which the lethal temperatures were around 100° C. For all three Geranium species and for one of the legume species, Anthyllis vulneraria, exposure temperatures above ca. 45° C resulted in dormancy release, and maximum germination occurred above 60-65° C. Speed of germination was little affected for most species, except after exposure to nearlethal temperatures, where it slowed down dramatically, although the seedlings emerging were healthy. We conclude that due to sharp temperature gradients in the soil during fire, differences in heat tolerance between species in most cases are not large enough to be a decisive factor in their post-fire colonising success. There are exceptions: the seeds of certain taxa that are impermeable to water in the dormant state, some of which have heat triggered germination.


Near Full-Length Genomic Characterization of Two Novel HIV Type 1 Second-Generation Recombinant Forms (CRF01_AE/CRF07_BC) from Guangxi, China.
CRF01_AE and CRF07_BC are the two predominant HIV-1 subtypes currently circulating in China. We identified here a novel CCR5-tropic HIV-1 second-generation recombinant form virus found in two individuals, (GX19017 and GX19032), which were isolated from two HIV-1-positive people in Guangxi, southwest China. Phylogenic analyses indicated that these two sequences were all composed of two well-established circulating recombinant forms (CRFs) CRF07_BC and CRF01_AE, with four recombinant breakpoints observed in the pol, vpu/env, and env gene regions, respectively. The recombinant CRF01_AE region was clustered with the previously described CRF01_AE subcluster 2 lineage, which was characterized by the susceptibility to phenotypic transfer. The genome structure is significantly different from other previously reported CRFs and unique recombination forms. The emergence of a series of novel recombinant strains is indicative of the burgeoning complexity of the HIV-1 epidemic among the sexually transmitted population. Meanwhile, it may furnish significant insights into the dynamics and intricacy of the HIV-1 epidemic in China.


alpha1-Adrenergic receptor in rat ovary: presence and localization.
Noradrenaline modulates ovarian steroidogenesis, stimulates ovulation, and probably promotes follicular development in the ovary. It has been suggested that these effects of noradrenaline are mediated by alpha- and/or beta-adrenergic receptors (ARs) in the ovary. The purpose of the present study was to examine whether alpha(1)-AR is present in the rat ovary. In Western blotting, antibody against alpha(1)-ARs recognized a major protein in the ovary of adult (10-week-old) rats with a molecular weight of 80 kDa, which is similar to that of the alpha(1B)-AR subtype. Immunohistochemistry using this antibody showed that alpha(1)-AR was detected at various sites in the ovary, including large antral follicle, germinal epithelium at the circumference of large antral follicle, corpus luteum, and interstitial tissue. These results confirm that the ovary contains alpha(1)-AR (probably alpha(1B)-subtype), and suggest that this receptor mediates some of the activities of noradrenaline in the regulation of ovarian functions. Furthermore, we found that alpha(1)-AR is present in oocyte of large antral follicle, suggesting that noradrenaline acts on oocyte via this receptor.


The value of systematic reviews in research.
Nurses may be deterred from using research to inform their practice because of the huge numbers of papers available on some topics. Literature reviews on a topic of interest may make the task easier. A systematic review aims to discover all the research undertaken on a subject and review all the results in a scientific manner. Systematic reviews may highlight findings not available from individual studies and can thus help to inform and improve practice.


Synthetic control devices for gene regulation in Penicillium chrysogenum.
Orthogonal, synthetic control devices were developed for Penicillium chrysogenum, a model filamentous fungus and industrially relevant cell factory. In the synthetic transcription factor, the QF DNA-binding domain of the transcription factor of the quinic acid gene cluster of Neurospora crassa is fused to the VP16 activation domain. This synthetic transcription factor controls the expression of genes under a synthetic promoter containing quinic acid upstream activating sequence (QUAS) elements, where it binds. A gene cluster may demand an expression tuned individually for each gene, which is a great advantage provided by this system. The control devices were characterized with respect to three of their main components: expression of the synthetic transcription factors, upstream activating sequences, and the affinity of the DNA binding domain of the transcription factor to the upstream activating domain. This resulted in synthetic expression devices, with an expression ranging from hardly detectable to a level similar to that of highest expressed native genes. The versatility of the control device was demonstrated by fluorescent reporters and its application was confirmed by synthetically controlling the production of penicillin. The characterization of the control devices in microbioreactors, proved to give excellent indications for how the devices function in production strains and conditions. We anticipate that these well-characterized and robustly performing control devices can be widely applied for the production of secondary metabolites and other compounds in filamentous fungi.


Knee and/or hip joint destruction in rheumatoid arthritis is associated with HLA-DRB1*0405 in Japanese patients.
To determine the prognostic factors for knee and/or hip joint destruction in rheumatoid arthritis (RA) patients, we typed 379 RA patients for HLA-DRB alleles and analysed the antigen frequencies. The DRB1*0405 antigen frequency in RA patients who underwent total knee replacement and/or total hip replacement was significantly higher than in those who did not have replacements, which meant that DRB1*0405 was associated with knee and/or hip joint destruction. This finding may be of value for predicting knee and/or hip joint destruction in RA.


Repurposing Ophthalmologic Timolol for Dermatologic Use: Caveats and Historical Review of Adverse Events.
Ophthalmic timolol solution is increasingly being repurposed as a topical therapeutic for a variety of dermatologic diseases, including pyogenic granulomas, infantile hemangiomas, and chronic wounds. There are no published guidelines or protocols for use in these indications in adults, and the dermatologic community may not be familiar with adverse events that have been extensively documented relating to its ophthalmic use. We review the evidence available relating to adverse events to topical timolol use to evaluate its safety in dermatologic applications and to alert clinicians to screening and monitoring that is needed when repurposing this drug for dermatologic use. The majority of serious adverse events associated with ophthalmic timolol were reported in the first 7 years of use, between 1978 and 1985, of which most common were cardiovascular and respiratory events, but also included 32 deaths. The available evidence suggests that ophthalmic timolol safety profiling may have been incomplete prior to widespread use. Recent clinical trials for dermatologic indications have focused on documenting efficacy and have not had rigorous monitoring for potential adverse events. Topical timolol may be safe and effective for the treatment of various dermatologic conditions in patients whose medical histories have been carefully reviewed for evidence of pre-existing cardiac or pulmonary disease and are monitored for potential adverse events. Despite the wide use of timolol in ophthalmologic practice, safe dermatologic repurposing requires recognition of the potential for facilitated systemic absorption though the skin and appreciation of its history of adverse events.


The extract, LXB-1, from the barks of Liriodendron × hybrid, induced apoptosis via Akt, JNK and ERK1/2 pathways in A549 lung cancer cells.
The effect of LXB-1, an extract from Liriodendron × hybrid, was determined on A549 human lung adenocarcinoma cell lines. Growth inhibition of LXB-1 was analyzed by MTT assay. Cancer cell cycle was measured by flow cytometry. To verify the apoptosis effect of LXB-1 on A549 cells, annexin V/PI double staining assay was performed. The expression levels of proapoptotic proteins were also measured by western blot. The potential mechanisms of LXB-1 inducing apoptosis - the expression and phosphorylation of ERK, p38, JNK and Akt - were investigated by western blot. The IC50 values of LXB-1 on A549 for 24, 48 and 72 h treatment were determined to be 12.97±1.53 μg/mL, 9.55±1.42 μg/mL, and 5.90±0.74 μg/mL, respectively. LXB-1 induced an obvious G2/M cell cycle arrest in A549 cells and resulted in significant cell apoptosis. LXB-1 also increased the cleavage of both caspase-3 and caspase-9, and greatly decreased the protein levels of Bcl-2. Moreover, LXB-1 increased the expression of phosphorylated JNK but decreased the levels of phosphorylated ERK1/2 and Akt. These results suggest that that LXB-1 induced apoptosis through JNK, ERK1/2, and Akt pathways in A549 cells.


Selected 1,3-Benzodioxine-Containing Chalcones as Multipotent Oxidase and Acetylcholinesterase Inhibitors.
Chalcones are considered effective templates for the development of monoamine oxidase (MAO) and cholinesterase (ChE) inhibitors. The present work describes the syntheses of selected 1,3-benzodioxine-containing chalcones (CD3, CD8 and CD10), and their inhibitory activities against MAO-A, MAO-B, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE). Compound CD8 most potently inhibited MAO-B with an IC50 value of 0.026 μM, followed by CD10 and CD3 (1.54 and 1.68 μM, respectively). CD8 potently and non-selectively inhibited MAO-A (IC50 value of 0.023 μM). On the other hand, CD10 and CD8 inhibited AChE with IC50 values of 5.40 and 9.57 μM, respectively. Kinetics and reversibility experiments showed that all synthesized molecules were competitive and reversible inhibitors, and the Ki values of CD8 for MAO-A and MAO-B were 0.018 and 0.0019 μM, respectively. By in vitro and in silico analyses, all compounds were found to have high passive human gastrointestinal absorptions, blood-brain barrier permeabilities, and non-toxicities. Molecular docking simulations revealed that docking affinity of each compound for MAO-B was higher than that for MAO-A. The results indicate that CD8 is a potent non-selective MAO inhibitor, and CD10 is an effective selective MAO-B inhibitor, and both possess AChE inhibitory activity. Therefore, we suggest that CD8 and CD10 be considered potential dual-targeting inhibitors of MAO and AChE for the treatment of various neurodegenerative disorders.


Effects of aortic root motion on wall stress in the Marfan aorta before and after personalised aortic root support (PEARS) surgery.
Aortic root motion was previously identified as a risk factor for aortic dissection due to increased longitudinal stresses in the ascending aorta. The aim of this study was to investigate the effects of aortic root motion on wall stress and strain in the ascending aorta and evaluate changes before and after implantation of personalised external aortic root support (PEARS). Finite element (FE) models of the aortic root and thoracic aorta were developed using patient-specific geometries reconstructed from pre- and post-PEARS cardiovascular magnetic resonance (CMR) images in three Marfan patients. The wall and PEARS materials were assumed to be isotropic, incompressible and linearly elastic. A static load on the inner wall corresponding to the patients' pulse pressure was applied. Cardiovascular MR cine images were used to quantify aortic root motion, which was imposed at the aortic root boundary of the FE model, with zero-displacement constraints at the distal ends of the aortic branches and descending aorta. Measurements of the systolic downward motion of the aortic root revealed a significant reduction in the axial displacement in all three patients post-PEARS compared with its pre-PEARS counterparts. Higher longitudinal stresses were observed in the ascending aorta when compared with models without the root motion. Implantation of PEARS reduced the longitudinal stresses in the ascending aorta by up to 52%. In contrast, the circumferential stresses at the interface between the supported and unsupported aorta were increase by up to 82%. However, all peak stresses were less than half the known yield stress for the dilated thoracic aorta.


A de novo CHD3 variant in a child with intellectual disability, autism, joint laxity, and dysmorphisms.
Chromodomain helicase DNA-binding (CHD) proteins play important roles in developmental processes. CHD3, a member of the CHD family of proteins, was reported to be a cause of a neurodevelopmental syndrome by Snijders Blok et al., but only a small number of probands have been reported. The patient was a 9-year-old female with severe intellectual disability, speech impairment, autism, joint laxity and dysmorphisms. Whole exome sequencing revealed a de novo missense variant in CHD3 (NM_001005273:exon18: c.2896C > T:p.R966W). We report a case with a pathogenic variant in the CHD3 gene. Our report indicates that CHD3 analysis is helpful for diagnosis of the cases with neurodevelopmental disorders, joint laxity, and coarse facial phenotype.


[Algodystrophy during pregnancy complicated by fracture of the femoral neck. Case report].
A case of 33 years old female with pathologic fracture of the femoral neck that occurred in the third trimester of pregnancy is presented. Generalized osteoporosis has been found in post-delivery radiographic examination. The patient has been operated with the Zespol hip-plate fixator.


Reduction of pathogenic bacteria from irrigation water through a copper-loaded porous ceramic emitter.
The increasing pathogenic bacteria threat in irrigation water has become a worldwide concern, prompting efforts to discover a new cost-effective method for pathogenic bacteria eradication, different than those currently in use. In this study, a novel copper-loaded porous ceramic emitter (CPCE) was developed via molded sintering method to kill bacteria from irrigation water. The material performance and hydraulic properties of CPCE are discussed herein, and the antibacterial effect against Escherichia coli (E. coli) and Staphylococcusaureus (S. aureus) was evaluated. The incremental copper content in CPCE improved flexural strength and pore size, which was conducive to enhancing CPCE discharge. Moreover, antibacterial tests showed that CPCE displayed efficient antimicrobial activity, killing 99.99% and more than 70% of S. aureus and E. coli, respectively. The results reveal that CPCE, with both irrigation and sterilization functions, can provide a low-cost and effective solution for bacterial removal from irrigation water.


[Abatacept].
Rheumatoid arthritis (RA) is an autoimmune disease that targets synovial joints and leads to bone destruction and joint deformity. T cell activations were shown to be involved in the onset of RA. T cells may control downstream inflammatory mediators reaching the synovium, where inflammation leads to joint destruction. However the treatment of RA has improved considerably in recent years through the introduction of DMARDs such as MTX, and anti-tumor necrosis factor therapy, there is still unmet medical need. Not a few patients experience an inadequate response to these therapies. Abatacept, a fusion protein of the extracellular domain of CTLA4 (a molecule inhibits the costimulatory pathway in T cell activation) and the Fc domain of human IgG1, was developed for the treatment of RA. Abatacept has shown long-term efficacy and safety in RA patients who were inadequate to MTX and/or anti-tumor necrosis factor therapy.


Semen Analysis in Cancer Patients Referred for Sperm Cryopreservation before Chemotherapy over a 15-Year Period in Korea.
This study evaluated the demographics and semen parameters of males with cancer who banked their sperm prior to chemotherapy. This is a retrospective study of 66 cases referred for sperm banking prior to initiation of chemotherapy over a 15-year period (1999~2014). Patients who had previously received cancer treatment including chemotherapy or radiotherapy were not included in this study. We studied a total of 66 cancer patients referred for cryopreservation of sperm prior to chemotherapy. The mean age of the patients at the time of banking was 32.0±7.9 years (range, 19~58 years). The types of cancer were testicular cancer (31 cases, 47.0%), non-Hodgkin's disease (10 cases, 15.1%), Hodgkin's disease (5 cases, 7.6%), leukemia (8 cases, 12.1%), gastrointestinal malignancy (5 cases, 7.6%), and musculoskeletal malignancy (5 cases, 7.6%). There were significant differences in sperm concentration and viability among the various types of cancer, but no significant difference in semen volume or sperm motility and morphology. In this study we found that sperm quality could decrease even before chemotherapy. Because chemotherapy can also negatively affect spermatogenesis, sperm cryopreservation prior to treatment should be strongly recommended for cancer patients of reproductive age.


Ventriculo-peritoneal shunt independence following successful treatment of Gram negative (E. coli) ventriculitis: Case report and review of the literature.
We report a case of tumour-related hydrocephalus in a child treated with a ventriculo-peritoneal shunt which subsequently became infected with gram negative bacteria (Escherichia coli). After successful treatment of the infection the patient became shunt independent and has remained so for over 2 years. Gram negative ventriculitis is associated with diminished cerebro-spinal fluid production and we discuss the literature to date regarding this phenomenon.


Significance tests. Part 3.
A discussion of basic parametric statistical tests of sample proportions and frequencies is concluded with a description of the chi-squared test. The treatment of distribution-free or non-parametric data is then illustrated with examples of the sign test and Wilcoxon's two-sample rank test.


Massively Systematic Transcript End Readout, "MASTER": Transcription Start Site Selection, Transcriptional Slippage, and Transcript Yields.
We report the development of a next-generation sequencing-based technology that entails construction of a DNA library comprising up to at least 4(7) (∼ 16,000) barcoded sequences, production of RNA transcripts, and analysis of transcript ends and transcript yields (massively systematic transcript end readout, "MASTER"). Using MASTER, we define full inventories of transcription start sites ("TSSomes") of Escherichia coli RNA polymerase for initiation at a consensus core promoter in vitro and in vivo; we define the TSS-region DNA sequence determinants for TSS selection, reiterative initiation ("slippage synthesis"), and transcript yield; and we define effects of DNA topology and NTP concentration. The results reveal that slippage synthesis occurs from the majority of TSS-region DNA sequences and that TSS-region DNA sequences have profound, up to 100-fold, effects on transcript yield. The results further reveal that TSSomes depend on DNA topology, consistent with the proposal that TSS selection involves transcription-bubble expansion ("scrunching") and transcription-bubble contraction ("anti-scrunching").