The effect of botulinum toxin on anxiety in cervical dystonia: A prospective, observational study.
Anxiety is present in 30-40% of patients with cervical dystonia (CD). It has been ascribed to a direct effect of the state of motor symptoms on related pain, disability, and disfigurement. Accordingly, any reported benefit of botulinum toxin (BoNT) on anxiety is thought to be secondary to its effect on the same. We sought to evaluate the distinctive impact of botulinum toxin (BoNT) on anxiety in cervical dystonia (CD). In this prospective observational study, 60 participants with idiopathic isolated CD were recruited from clinic. We assessed motor and anxiety burden using Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) parts I-III and State-Trait Anxiety Inventory (STAI). Assessments were done at time of BoNT (baseline) and at 6 weeks post-injection. STAI and motor severity TWSTRS scores poorly correlated at the baseline visit (rho = -0.30, p = 0.411). Both, motor TWSTRS (Mdifference = -1.46, p < 0.024) and STAI (Mdifference = -10.37, p = 0.007) improved from baseline to 6 weeks (peak effect). The change in motor TWSTRS poorly correlated with change in anxiety scores from baseline visit to 6 weeks (rho = -0.14, p > 0.999). Of these measures of anxiety, improvement in STAI-T had the largest effect size (rank biserial = 0.52). BoNT improves both motor severity and anxiety in CD. Poor correlation between motor severity and anxiety at both the time of injection and during the time of peak effect, and improvement in trait anxiety suggests that BoNT has a direct beneficial effect on anxiety.


A novel technique for the percutaneous removal of tricuspid valve vegetations utilizing the Inari Flowtriever System.
Right-sided infective endocarditis is a common entity for which surgical intervention is frequently high-risk. Considering its invasive nature, potential complications, and challenging patient population, a less invasive endovascular option is desirable. The previous series have demonstrated the feasibility of percutaneous therapy for tricuspid valve (TV) vegetation utilizing a filter-based bypass circuit. However, the limited availability of a specialized team, resources, procedural complexity, and large bore sheath size restrict the broad adoption of this technique. The Inari FlowTriever System (Inari Medical) is an endovascular, catheter-based, aspiration, and mechanical thrombectomy system indicated for the removal of large-volume venous thrombus and pulmonary emboli. Independent of anesthesia, perfusion, or advanced imaging, this device's characteristics uniquely improve the operator's ability to safely remove unwanted debris from complex anatomy. This report describes the first, utilization of the Inari FlowTriever System for the removal of massive and inoperable TV vegetation.


Amidization of doxorubicin alleviates doxorubicin-induced contractile dysfunction and reduced survival in murine cardiomyocytes.
Doxorubicin is an effective anthracycline used for cancer therapy. However, the clinical application of doxorubicin has been largely limited by its irreversible cardiotoxicity, which is mainly induced by the primary amine group. In this study, we structurally modified doxorubicin by converting the primary amine into an acid-labile amide before assessing the acute cardiac effect of doxorubicin (pristine or modified) on cardiomyocyte contractile function. Contractile properties of murine cardiomyocytes were analyzed including peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR(90)) and maximal velocity of shortening/re-lengthening (+/-dL/dt). Cell toxicity and survival rate were evaluated using the MTT assay. The doxorubicin-free base was amidized by reacting with 3,4,5,6-tetrahydophthalic anhydride (THPA) or 3,3,4,4-tetramethylsuccinic anhydride (TMSA) to yield doxorubicin-THPA or -TMSA. Acute exposure of pristine doxorubicin (10(-9)-10(-5)M) for 30 min significantly prolonged TPS and TR(90) without affecting PS and +/-dL/dt. Interestingly, doxorubicin-induced prolongation of TPS and TR(90) was significantly attenuated or abrogated by amidization of doxorubicin. Neither doxorubicin-THPA nor -TMSA affected PS and +/-dL/dt. ROS and MTT assay revealed significantly reduced ROS production and cardiac cell toxicity from amidized doxorubicin compared with the pristine compound. Comparable cytotoxicity in human ovarian cancer SKOV-3 cells was observed between amidized and pristine doxorubicin compounds. These data provide evidence for the first time that structural modification of doxorubicin alleviates its cardiac toxicity.


Cytokinin vectors mediate marker-free and backbone-free plant transformation.
Conventional Agrobacterium-mediated transformation methods rely on complex and genotype-specific tissue culture media for selection, proliferation, and regeneration of genetically modified cells. Resulting transgenic plants may not only contain selectable marker genes but also carry fragments of the vector backbone. Here, we describe a new method for the production of transgenic plants that lack such foreign DNA. This method employs vectors containing the bacterial isopentenyltransferase (ipt) gene as backbone integration marker. Agrobacterium strains carrying the resulting ipt gene-containing "cytokinin" vectors were used to infect explants of various Solanaceous plant species as well as canola (Brassica napus). Upon transfer to hormone-free media, 1.8% to 9.9% of the infected explants produced shoots that contained a marker-free T-DNA while lacking the backbone integration marker. These frequencies often equal or exceed those for backbone-free conventional transformation.


Is akathisia associated with poor clinical response to antipsychotics during acute hospital treatment?
Previous studies have suggested that akathisia is associated with poor acute clinical response to antipsychotics and that low serum iron levels are associated with emergence of akathisia. To examine these relationships during routine clinical treatment, we studied patients with DSM-IV schizophrenia or schizoaffective disorder undergoing hospital treatment for acute psychotic exacerbations with doctor's choice medications. There were 34 subjects observed for at least 2 weeks. They were assessed at baseline and weekly by one rater with the Anchored Brief Psychiatric Rating Scale and by another rater with the Barnes Rating Scale for akathisia, with the two raters blind to each other's ratings. Serum ferritin and transferrin levels were obtained at baseline. Seventeen subjects developed akathisia. Subjects with and without akathisia did not differ in change in thinking disturbance or anxiety-depression scores over 2 weeks, or in serum ferritin or transferrin levels. We conclude that mild akathisia by itself is not strongly associated with initial response to low to moderate doses of antipsychotics in the acute clinical setting. Limitations of the study are discussed.


Structural genomics of infectious disease drug targets: the SSGCID.
The Seattle Structural Genomics Center for Infectious Disease (SSGCID) is a consortium of researchers at Seattle BioMed, Emerald BioStructures, the University of Washington and Pacific Northwest National Laboratory that was established to apply structural genomics approaches to drug targets from infectious disease organisms. The SSGCID is currently funded over a five-year period by the National Institute of Allergy and Infectious Diseases (NIAID) to determine the three-dimensional structures of 400 proteins from a variety of Category A, B and C pathogens. Target selection engages the infectious disease research and drug-therapy communities to identify drug targets, essential enzymes, virulence factors and vaccine candidates of biomedical relevance to combat infectious diseases. The protein-expression systems, purified proteins, ligand screens and three-dimensional structures produced by SSGCID constitute a valuable resource for drug-discovery research, all of which is made freely available to the greater scientific community. This issue of Acta Crystallographica Section F, entirely devoted to the work of the SSGCID, covers the details of the high-throughput pipeline and presents a series of structures from a broad array of pathogenic organisms. Here, a background is provided on the structural genomics of infectious disease, the essential components of the SSGCID pipeline are discussed and a survey of progress to date is presented.


Assessment of the genotoxic/clastogenic potential of coumarin derivative 6,7-dihydroxycoumarin (aesculetin) in multiple mouse organs.
6,7-Dihydroxycoumarin (6,7-HC) (aesculetin) is a natural and synthetic coumarin derivative of great interest for use by humans due to their potent antioxidant properties. Considering that there are no reports that assess the in vivo genetic toxicity of 6,7-HC, the aim of the present study was to investigate its genotoxic potential in terms of DNA damage in peripheral blood, liver, bone marrow and testicular cells of Swiss albino mice by the comet assay, and its clastogenic/aneugenic potential in bone marrow cells using the micronucleus test. In addition, the ability of 6,7-HC to modulate the genotoxic effects induced by doxorubicin (DXR) was also preliminarily evaluated. Cytotoxicity was assessed by scoring polychromatic (PCE) and normochromatic (NCE) erythrocytes' ratio. The test compound was administered orally at doses of 25, 50 and 500 mg kg-1 isolated and also simultaneously to DXR (80 mg kg-1). The results showed that 6,7-HC did not induce significant DNA damage in any of the analyzed cells, and also did not show any significant increase in micronucleated PCE at the three tested doses. The PCE/NCE ratio indicated no cytotoxicity. Moreover, the extent of DNA damage induced by DXR decreased significantly only in peripheral blood and testicular cells, and only at the lowest dose of 6,7-HC.


A Team-Based Approach to Introduce and Sustain the Use of the WHO Surgical Safety Checklist in Tanzania.
Millions of patients worldwide suffer disability and death due to complications related to surgery. Many of these complications can be reduced by the use of the World Health Organization (WHO) Surgical Safety Checklist (SSC), a simple tool that can enhance teamwork and communication and improve patient safety. Despite the evidence on benefits of its use, introducing and sustaining the use of the checklist are challenging. We present a team-based approach employed in a low-resource setting in Tanzania, which resulted in high checklist utilization and compliance rates. We reviewed reported data from facility registers supplemented by direct observation data by mentors to evaluate the use of the WHO SSC across 40 health facilities in two regions of Tanzania between January and December 2018. We analyzed the self-reported monthly data on total number of major surgeries performed and proportion of surgeries where the checklist was used. We also analyzed the use of the SSC during direct observation by external mentors and completion rates of the SSC in a random selection of patient files during two mentorship visits between June and December 2018. During the review period, the average self-reported checklist utilization rate was 79.3% (11,564 out of 14,580 major surgeries). SSC utilization increased from 0% at baseline in January 2018 to 98% in December 2018. The proportion of checklists that were completely and correctly filled out increased between the two mentor visits from 82.1 to 92.8%, but the gain was significantly greater at health centers than at hospitals (p < 0.05). Health centers (which had one or two surgical teams) self-reported a higher checklist utilization rate than hospitals (which had multiple surgical teams), i.e., 99.4% vs 68.8% (p < 0.05). Our findings suggest that Surgical Safety Checklist implementation is feasible even in lower-resource settings. The self-reported SSC utilization rate is higher than reported in other similar settings. We attribute this finding to the team-based approach employed and the ongoing regular mentorship. We recommend use of this approach to scale-up checklist use in other regions in the country as recommended in the Ministry of Health of Tanzania's National Surgical, Obstetric, and Anesthesia Plan (NSOAP).


Exploring the use of Routine Outcome Monitoring in the treatment of patients with a psychotic disorder.
Routine Outcome Monitoring (ROM) has become part of the treatment process in mental health care. However, studies have indicated that few clinicians in psychiatry use the outcome of ROM in their daily work. The aim of this study was to explore the degree of ROM use in clinical practice as well as the explanatory factors of this use. In the Northern Netherlands, a ROM-protocol (ROM-Phamous) for patients with a psychotic disorder has been implemented. To establish the degree of ROM-Phamous use in clinical practice, the ROM results of patients (n=204) were compared to the treatment goals formulated in their treatment plans. To investigate factors that might influence ROM use, clinicians (n=32) were asked to fill out a questionnaire about ROM-Phamous. Care domains that were problematic according to the ROM-Phamous results were mentioned in the treatment plan in 28% of cases on average (range 5-45%). The use of ROM-Phamous in the treatment process varies considerably among clinicians. Most of the clinicians find ROM-Phamous both useful and important for good clinical practice. In contrast, the perceived ease-of-use is low and most clinicians report insufficient time to use ROM-Phamous. More frequent ROM use should be facilitated in clinicians. This could be achieved by improving the fit with clinical routines and the ease-of-use of ROM systems. It is important for all stakeholders to invest in integrating ROM in clinical practice. Eventually, this might improve the diagnostics and treatment of patients in mental health care.


Trophoblast invasion: assessment of cellular models using gene expression signatures.
Invasive, extravillous trophoblasts (EVT) of the human placenta are critically involved in successful pregnancy outcome since they remodel the uterine spiral arteries to increase blood flow and oxygen delivery to the placenta and the developing fetus. To gain more insights into their biological role different primary cell culture models are commonly utilised. However, access to early placental tissue may be limited and primary trophoblasts rapidly cease proliferation in vitro impairing genetic manipulation. Hence, trophoblastic cell lines have been widely used as surrogates to study EVT function. Although the cell lines share some molecular markers with their primary counterpart, it is unknown to what extent they recapitulate the invasive phenotype of EVT. Therefore, we here report the first thorough GeneChip analyses of SGHPL-5, HTR-8/SVneo, BeWo, JEG-3 and the novel ACH-3P trophoblast cells in comparison to previously analysed primary villous cytotrophoblasts (CTBs) and extravillous trophoblasts (EVTs). Analyses of approximately 14,000 commonly expressed genes revealed that EVTs most closely resemble CTBs with considerable differences to the group of choriocarcinoma cells (JEG-3, BeWo, ACH-3P) and the group of SV40 Large T Antigen-selected cell types (SGHPL-5, HTR-8/SVneo). Similarly, analyses of 912 genes discriminating EVT from CTB, or 370 EVT-specific genes did not unravel a particular cell line with close similarity to any of the primary cell types, although molecular signatures common to EVT and each group of cell lines could be identified. Considering the diversity of mRNA expression patterns it is suggested that molecular studies in trophoblast cell lines require verification of the critical steps in an appropriate primary model system.


The Stamey bladder neck suspension operation for stress incontinence and neurovesical dysfunction.
Twelve patients with neurovesical bladder dysfunction and genuine stress incontinence were treated by the Stamey operation. The technique is described together with some minor modifications that we have found useful. Results have been encouraging and 11 of the 12 patients have been cured of incontinence.


Evaluation of the quality of life in children and adolescents with type 1 diabetes in two health institutions, Bogotá, D. C., Colombia
Introduction: Diabetes mellitus is one of the most prevalent chronic diseases in the pediatric and juvenile population that affects the quality of life of patients. Objective: To evaluate the quality of life of a pediatric population under 18 years of age diagnosed with type 1 diabetes from two pediatric institutions in the city of Bogotá. Material and methods: We collected of sociodemographic data and clinical variables and application of the PedsQL 4.0™ questionnaire, and the diabetes module 3.2 version validated in Spanish. The sociodemographic data, the clinical variables and the PedsQL™ were processed in the statistical software Stata 17™. Results: In the global score of the PedsQL™ 3.2, diabetes version, men presented better quality of life compared to women. The correlation between the hemoglobin A1c (HbA1c) values and the PedsQL scale in the global score was evaluated. Patients with HbA1c values below 9% presented a better health-related quality of life, while in the group with HbA1c greater than 9% a perception of low quality of life was observed (p=0.025). Regarding the type of therapy and the relationship with the domains of the PedsQL 3.2, diabetes version, patients who used insulin pumps had better scores in the domains barriers, adherence, concern, communication and in the global score compared to patients who used multiple daily injections of insulin as treatment (p=0.0363). Conclusions: In our patients, a better metabolic control (measured by the HbA1c value) and the use of an insulin pump contribute to a better perception of quality of life.


Using sports to strengthen resiliency in children. Training heart.
This article describes how sports can cultivate resiliency. Encouraging the development of heart in youth is highlighted. The concept is a simple one. By encouraging children and adolescents to go the extra mile in a sports context, youth practice calling up emotional reserves until they trust that they have a stockpile of conviction. The authors believe building heart in youth is a preventive public health strategy that can inoculate against the potentially negative effects of stress and trauma. It is hoped that heart will become an essential tool in the primary prevention of stress-related disorders in youth and a critical skill that promotes having an optimal life. In addition, the authors believe that heart can be developed after exposure to traumatic stress. Heart is critical to overcoming the sense of devastation and helplessness that develops from traumatic experiences.


Significance of O-Arm Assisted Anterior Controllable Antedisplacement and Fusion Surgery in Treatment of Cervical Ossification of Posterior Longitudinal Ligament.
Anterior controllable antedisplacement and fusion (ACAF) surgery for cervical OPLL is commonly used in clinical practice and has shown promising results. Nonetheless, precise slotting and lifting are the most critical procedures in ACAF surgery to avoid several unique and dangerous problems, such as residual ossification and incomplete lifting. C-arm intraoperative imaging can help with traditional cervical surgery but not with the precise slotting and lifting operation in ACAF surgery. Fifty-five patients admitted to our department with cervical OPLL were retrospectively enrolled. Given the selection of intraoperative imaging technique, patients were divided into the C-arm group and O-arm group. The operation time, intraoperative blood loss, hospital stay, Japanese Orthopaedic Association score, Oswestry Disability Index score, visual analog scale score, slotting grade, lifting grade, and complications were recorded and analyzed. At the final follow-up, all patients acquired satisfactory improvement of neurologic function. Patients in the O-arm group, on the other hand, had a better neurologic state 6 months after surgery and at the final follow-up than those in the C-arm group. Furthermore, slotting and lifting grade were considerably higher in the O-arm group than in the C-arm group. No severe complications were encountered in both groups. O-arm assisted ACAF can achieve accurate slotting and lifting, which might effectively reduce the occurrence of complications and is worthy of clinical application.


Novel combination therapy of pedal arch angioplasty and dual distal bypass as an alternative treatment option for vasculitis in patients with chronic limb-threatening ischemia.
A 68-year-old man with chronic limb-threatening ischemia caused by atypical vasculitis was successfully treated by the combination of pedal arch angioplasty and dual distal bypass. Angioplasty alone failed; therefore, we performed pedal arch angioplasty followed by distal bypass revascularized to the newly created dorsalis pedis artery and posterior tibial artery anastomosis sites. Restenosis occurred twice, and both cases were successfully treated by immediate angioplasty. Both branches of the graft remained patent for >2.5 years, and the wound healed completely. This unique combination of techniques can provide favorable results for selected patients with chronic limb-threatening ischemia.


A new 111In-bleomycin complex for tumor imaging: preparation, stability, and distribution in glioma-bearing mice.
A new 111In-bleomycin complex (111In-BLMC) is here reported. Its radiochemical purity was 99% by thin-layer chromatography (TLC) (Rf 0.65) and in 5% agarose gel electrophoresis in 0.02 M NaHCO3 it migrated toward the anode. Autoradiographs of TLC and gel electrophoresis plates showed no change on storage for 3 weeks. Urine and plasma from untreated or glioma-bearing mice after injection of 111In-BLMC were analyzed by TLC and gel electrophoresis. Results indicated stability in vivo, nonbinding to transferrin, affinity to viable tumor, and excretion faster than 111In-BLM-B2, 111In-BLM, or 57Co-BLM. Tissue distributions 24 hr after injection of radiopharmaceutical showed activity ratios of tumor to blood, muscle, and brain of 13.1, 12.4, and 81.6, respectively, which were significantly higher than those for previously prepared 111In-BLM-B2 or 111In-BLM (except for brain, 0.05 less than P less than 0.1). The new 111In-BLM complex may be useful in clinical imaging and for combining radionuclide radiotherapy and chemotherapy.


Discovery of the programmed cell death-1/programmed cell death-ligand 1 interaction inhibitors bearing an indoline scaffold.
Inhibiting the programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway is an attractive strategy for tumor immunotherapy. Here, a novel series of indoline-containing compounds were developed, among which, A13 was identified as the most promising PD-1/PD-L1 pathway inhibitor. At the biochemical level, A13 demonstrated strong inhibition of the PD-1/PD-L1 interaction, with an IC50 of 132.8 nM. Notably, it exhibited outstanding immunoregulatory activity, and significantly elevated interferon-γ secretion in a Hep3B/OS-8/hPD-L1 and CD3 T cell co-culture model, without significant toxic effect. Therefore, A13 could be employed as a suitable lead compound for further design of non-peptide inhibitors targeting the PD-1/PD-L1 interaction. In addition, the preliminary structure-activity relationships of these new indoline compounds were investigated in this study, providing valuable information for future drug development.


A highly sensitive and precise radioenzymatic assay for plasma epinephrine and norepinephrine.
A modification of the procedures for simultaneous radiometric determinations of plasma epinephrine (E) and norepinephrine (NE) was developed. High performance liquid chromatography (HPLC) is excellently suited to separate the radioactive products of the enzymatic methylation of catecholamines. The time-saving procedure shows significant advantages as against the conventional method of isolating normetanephrine and metanephrine by thin layer chromatography. The high sensitivity (detection limit = 1 pg), specifity, and good precision (cv = 6%) of this assay are demonstrated.


Efficacy and safety of immune checkpoint inhibitors in colorectal cancer: a systematic review and meta-analysis.
Immune checkpoint inhibitor (ICI) therapies have shown promising prospects in colorectal cancer (CRC) immunotherapy; many clinical trials have been carried out. In this study, we sought to evaluate the efficacy and safety of ICI therapies in CRC by presenting a meta-analysis of relevant studies. Databases including PubMed, Embase, Cochrane Library, and Web of Science were systematically searched for studies concerning the efficacy and safety of ICI in colorectal cancer. The reported odds ratio (OR) or weighted mean difference (WMD) with 95% confidence intervals (CIs) of overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), treatment-related adverse events (TRAEs), and TRAEs ≥ 3 in the included studies were analyzed by fixed effects/random effects models. Three studies involving 667 patients with colorectal cancer were included in our meta-analysis. No significant difference between the immune checkpoint inhibitor therapies and conventional therapies in OS (WMD = 0.73, 95% CI - 3.09, 4.54; p = 0.71), in ORR (OR = 1.54, 95% CI 0.98, 2.40; p = 0.06), and in DCR (OR = 0.97, 95% CI 0.36, 2.61; p = 0.95). The median PFS of the ICI therapy group was shorter than that of the conventional therapy group (WMD = - 0.10, 95% CI - 0.18, - 0.02; p = 0.02). At the same time, we also could not find a significant difference between the immune checkpoint inhibitor therapies and conventional therapies in TRAEs (OR = 1.56, 95% CI 0.11, 22.09; p = 0.74) and in TRAEs ≥ 3 (OR = 0.94, 95% CI 0.16, 5.65; p = 0.95). Immune checkpoint inhibitor therapies could not improve all survival endpoints to advanced or metastatic colorectal cancer patients. Whether immune checkpoint inhibitors should be the first choice of therapies for colorectal cancer patients with undetermined microsatellite status or not able to determine microsatellite status needs more related studies to prove.


Clinical risk factors for complete and partial placental retention - a case-control study.
We sought to investigate the incidence, maternal risk factors, and perinatal outcomes of women with complete and partial placental retention in a tertiary care teaching hospital in Southwestern Germany. We performed an unmatched case-control study with cases occurring between July 2000 and June 2007. Women were included into the study if they completed at least the 24th week of gestation and were diagnosed with placental retention requiring surgical intervention. We selected two controls per case and performed univariate and multivariate logistic regression analyses to identify risk factors for complete and partial placental retention. A total of 161 cases (2.02%) were identified out of 7978 deliveries. The 1-year prevalence of all types of placental retention continuously increased during the 6-year study period from 0.93% to 3.26%. A significant independent risk factor for all types of placental retention in the multivariate logistic regression model was a previous retention of the placenta [odds ratio (OR)=21.723, 95% confidence interval (CI) 6.07-77.7]. Independent protective factors against all types of placental retention were a non-anterior and non-posterior placenta location (OR=0.561, 95% CI 0.35-0.91), and a cesarean delivery with (OR=0.193, 95% CI 0.09-0.40) and without labor (OR=0.482, 95% CI 0.27-0.86). Women without partial placental retention delivered neonates with better 5-min APGAR scores (OR=0.78, 95% CI 0.65-0.95). A thorough medical history and a vigilant prepartum ultrasound help in identifying women at risk for placental retention.


Thonningiiflavanonol A and thonningiiflavanonol B, two novel flavonoids, and other constituents of Ficus thonningii Blume (Moraceae).
A phytochemical study of Ficus thonningii has led to the isolation of two previously unreported compounds, thonningiiflavanonol A and thonningiiflavanonol B together with 16 known compounds: shuterin, naringenin, syringic acid, p-hydroxybenzoic acid, genistein, 5,7,3',4',5'-pentahydroxyflavanone, luteolin, methylparaben, aromadendrin, garbanzol, dihydroquercetin, 5,7,3'-trihydroxyflavanone, β-sitosterol, sitosterolglucoside, lupeol acetate, and taraxerol. Their structures were elucidated on the basis of spectroscopic data. The new compounds and extracts displayed potent antioxidant activity.


The Association of the Health Management Strategy with Subjective Health and Well-being Outcomes in General Population.
People face many obstacles to overcoming crisis in life and proactively manage life crises. This study aimed to evaluate the association of self-management strategy with subjective health and well-being for the general South Korean population. We recruited 1,200 respondents using an equal-probability sampling method from March to May 2018. A questionnaire including life version of the Smart Management Strategy for Health Assessment Tool (SAT-Life), the five Health Status Questionnaire, Short Form-12, McGill Quality of Life Questionnaire (MQOL), Patient Health Questionnaire-9 (PHQ-9), and Satisfaction With Life Scale (SWLS) was administered to participants. In multiple stepwise logistic regression model adjusted with basic demographic variables (age, sex, region, education and monthly income level), core strategy was independently associated with physical, mental, social, spiritual, and general health status (adjusted odds ratios [aORs], 1.97-2.92). Preparation strategy was independently associated with physical, mental, spiritual, and general health status (aORs, 2.36-3.31). Implementation strategy was independently associated with physical, social, spiritual, and general health status (aORs, 2.22-2.42). Core strategy and implementation strategy were independently associated with higher Physical Component Score (aORs, 2.21-2.29) and higher Mental Component Score (aORs, 1.68-1.76). Core strategy and preparation strategy were independently associated with lower PHQ-9 (aORs, 2.63-3.74). Pearson's correlation coefficients between scores on SAT-Life and the other factors (MQOL social support, MQOL spiritual well-being, and SWLS) explain having significant correlations ranging from 0.41-0.43. Self-management strategies of health might be encouraged to manage subjective health and well-being outcomes.


Do proficiency testing participants learn from their mistakes? Experience from the EXCEL throat culture module.
Participation in proficiency testing is required under the Clinical Laboratory Improvement Amendments of 1988. Although the primary purpose of this testing is evaluation of current laboratory performance, a major secondary benefit of such testing is postulated to be progressive improvement in laboratory performance over time as laboratories learn from their previous experiences and feedback. To test the hypothesis that a secondary result of proficiency testing is improvement over time of laboratory performance. The performance of participants in a large proficiency testing program (EXCEL), designed for clinic and office laboratories, on a specific problematic competence, the ability to differentiate group A streptococcus from group C streptococci, was monitored during a 6-year period (1996-2001) for changes in participant performance. With each testing cycle, feedback on performance relative to peers and an educational discussion analyzing performance and suggesting best practices was submitted to participants. Despite consistent feedback, there was no significant change in participant performance throughout the period studied. In a large, stable proficiency testing program, a significant throat culture competence, which demonstrated less than optimal performance, did not improve over time, suggesting that current utilization of proficiency testing results in laboratory improvement programs is suboptimal.


[Congenital cytomegalovirus infection and cortical/subcortical malformations].
Intrauterine infection due to cytomegalovirus is the most common of the intrauterine viral/parasitic infections that affect the central nervous system and cause permanent lesions in the cortex as well as the subcortical white matter. Studies using brain magnetic resonance imaging (MRI) are limited. Six patients (4 females and 2 males) were studied in the first months of life in order to make a diagnosis of congenital cytomegalovirus, and identify the cortical and subcortical lesions using the necessary MRI sequences. The six patients showed malformations of cortical development (MDC) (schizencephaly, polymicrogyria or lissencephaly-pachygyria) from the neonatal period, and diffuse changes of the white matter, which remained with few changes during the first two years. They then began reducing in size in the form of high signal areas in T2, restricted to certain areas, and were evident for a few years more with little change. Intrauterine infection due to cytomegalovirus causes changes in the cortical grey matter, which consists of MDC, and in the subcortical white matter. The latter show a changing aspect as they appear as diffuse and wide areas of high signal intensity, which is usually due to delay in myelinisation, but could also be caused directly by the cytomegalovirus. These changes in the white matter are subjected to morphological changes throughout the first years of life, leading to brain atrophy. The neurological sequelae of these lesions left by these alterations are severe and chronic.


'Stability' of the fouling communities on the pilings of two piers in South Australia.
The subtidal communities of sessile organisms on the pilings of two piers were observed by photography of fixed quadrats over a period of two years. Data are presented on species-composition, relative abundance of species, and maximum longevities of individuals and colonies. The fluctuations in various properties of the communities (e.g. measures of species diversity, and percentage vovers of species and phyletic groups) are tested by a priori defined criteria for "narrow stochastic boundedness" and most are found to be narrowly bounded, despite considerable turnover of space. We conclude that most properties of the community vary less through time-that is, the community is in a sense more "stable"-than fouling communities previously studied using small plates immersed for relatively short periods. Long-lived species are relatively more abundant on the pilings than in plate-studies. These differences are attributed to the large size and long period of submersion of the pilings. Our results appear similar to those of other studies on large, old substrata.


Update on the diagnosis and management of malignant phyllodes tumors of the breast.
Malignant phyllodes tumors of the breast are a rare entity. They occur infrequently but most often in younger women in comparison to typical epithelial-based breast cancers. Treatment of these tumors is not without controversy and in this review we will present an update on the diagnosis and management of malignant phyllodes tumors of the breast.


Temporal evolution of anemia in children aged six to 59 months in the state of Pernambuco, Brazil, 1997 to 2016.
To analyze the temporal evolution of anemia in children aged six to 59 months in Pernambuco, based on population surveys from 1997, 2006, and 2016 and the factors associated with the situation in 2016. The field studies took place in the participants' households, in the Recife Metropolitan Area, as well as in the urban and rural inland. The trend study of anemia in children used data from the State Health and Nutrition Survey (Pesquisa Estadual de Saúde e Nutrição - PESN) II (40.9%) and III (32.8%). Data from PESN IV were collected using questionnaires administered to families to verify socioeconomic and individual conditions, as well as anthropometric - weight and height - and biochemical - hemoglobin - records. We adopted the test for trend in proportion for the time trend study and Poisson regression for hypothesis tests for the associated factors. Statistically significance was set at a p-value<0.05. In 2016, the prevalence of anemia was 24.2%, indicating a significant reduction in disease incidence. In children aged 6-23 months, this number decreased from PENS II and III to PENS IV - 63 and 55.6 to 37.7% (p<0.001), respectively. In 2016, the statistically significant variables for anemia in children were maternal hemoglobin, child's age, current or recent case of diarrhea, and weight-for-age index. Between 1997 and 2016, anemia rates decreased, showing an epidemiological trend that can contribute to continuously improve the health of children under five years of age in Pernambuco.


A locking endurance test for hinged sections of removable partial dentures.
In this study an apparatus is described that will open and close a hinged section of a removable partial denture. A metal framework based on a "swinglock" type of hinge and latch design was constructed. An electric motor provided the drive for the opening and closing mechanism, which when operated set the device in motion. The device and results of a test run of 12,000 opening and closing operations are discussed.


NSCLC Evolution Studies Refine Biomarkers.
The latest analyses from TRACERx, a major effort to understand the genetic landscape of non-small cell lung cancer, are helping researchers uncover new, potentially prognostic biomarkers and pinpoint T-cell receptors that may be useful in the development of adoptive cellular immunotherapies.


Optimizing accuracy and precision of micro-coil localization in active-MR tracking.
To examine whether a centroid peak detection algorithm and micro-transmit tracking improve the accuracy and precision of active-MR tracking when combined with previously published strategies of Hadamard Multiplexing and Phase-field Dithering. The dipole magnetic field of a solenoid tracking coil was modeled and MR spin excitation using both a uniform body coil and the tracking coil was simulated for 5329 orientations of the solenoid coil with respect to B0. A lumenless micro-coil was built onto a rotation platform and MR-tracking accuracy and precision were experimentally assessed for 576 orientations within a 1.5-T MRI scanner. Peak identification strategies (i.e. maximum pixel detection and the centroid pixel method) and transmit modes (body transmit and micro-transmit tracking) were employed and localization accuracy was assessed for each orientation in both simulation and experimentation. The simultaneous use of the centroid pixel method, micro-transmit tracking, Phase-field Dithering, and Hadamard Multiplexing resulted in high MR tracking accuracy and precision: 0.52±0.41 mm and 0.34 mm respectively. Furthermore, all four methods combined offered a tracking error less than the size of the micro-coil, despite the lack of a signal source within the micro-coil. Micro-transmit tracking and the centroid pixel method improve MR tracking accuracy and precision when combined with Phase-field Dithering and Hadamard Multiplexing compared to using Phase-field Dithering and Hadamard Multiplexing alone.


Prevention of deep venous thrombosis in ambulatory or discharged orthopaedic patients. Actual management.
In recent years the problem of deep venous thrombosis (DVT) in outpatients and discharged patients has grown into a medical and juridical problem. In traumatology certain recommendations and statistical material exist: similar recommendations were made by the Berufsverband der Arzte für Orthopädie, Germany, pointing out the lack of sufficient statistical material. With the present study we tried to evaluate the actual management of DVT in discharged patients or outpatients in leading orthopaedic hospitals. The results from December 1993 reveal an inhomogeneous procedure which does not precisely follow the above recommendations. However, most orthopaedic surgeons agree that either general or individual means to prevent DVT should be available for ambulatory and discharged patients with plaster immobilisation of the leg according to presently accepted standards, i.e. low-dose heparin or low-molecular-weight heparins. Reduced weight-bearing, in contrast, is considered not to require preventive heparinisation to any great extent.


Photoelectrocatalysis based on Ti/TiO2 nanotubes removes toxic properties of the azo dyes Disperse Red 1, Disperse Red 13 and Disperse Orange 1 from aqueous chloride samples.
This work describes the efficiency of photoelectrocatalysis based on Ti/TiO2 nanotubes in the degradation of the azo dyes Disperse Red 1, Disperse Red 13 and Disperse Orange 1 and to remove their toxic properties, as an alternative method for the treatment of effluents and water. For this purpose, the discoloration rate, total organic carbon (TOC) removal, and genotoxic, cytotoxic and mutagenic responses were determined, using the comet, micronucleus and cytotoxicity assays in HepG2 cells and the Salmonella mutagenicity assay. In a previous study it was found that the surfactant Emulsogen could contribute to the low mineralization of the dyes (60% after 4 h of treatment), which, in turn, seems to account for the mutagenicity of the products generated. Thus this surfactant was not added to the chloride medium in order to avoid this interference. The photoelectrocatalytic method presented rapid discoloration and the TOC reduction was ≥87% after 240 min of treatment, showing that photoelectrocatalysis is able to mineralize the dyes tested. The method was also efficient in removing the mutagenic activity and cytotoxic effects of these three dyes. Thus it was concluded that photoelectrocatalysis was a promising method for the treatment of aqueous samples.


Spatial-frequency-specific inhibition in cat striate cortex cells.
Responses to single and multiple spatial frequency gratings were recorded from eighty-eight cat striate cortex cells. A cell's response to a grating of its optimum spatial frequency (f) was examined both alone and in the presence of gratings of 1/4, 1/3, 1/2, 2, 3 and 4f, respectively. Some 97% (thirty-seven of thirty-eight) of all simple cells showed significant inhibition of f by one or more of the other frequencies. This inhibition was usually fairly narrowly tuned, with only one or two spatial frequencies producing significant inhibition. Thirty-four simple cells were maximally inhibited by a higher frequency, three by a lower spatial frequency. By far the most common interaction was a considerable inhibition of f by 2f and/or 3f. Of the thirty-seven simple cells showing inhibition to a complex grating, seventeen responded in a manner dependent on the relative phases of the two components. Some showed only inhibition of f; in others, the response to f was either increased or decreased, depending on the relative phase of the two frequencies. The other twenty simple cells showed phase-independent inhibition: the inhibition was of approximately equal amplitude regardless of the relative phase angle of the two grating components. Such phase-independent inhibition cannot be accounted for by linear summation within classical cortical receptive fields. Only eighteen of forty-eight (38%) of the complex cells showed significant inhibition of f by one or more other spatial frequencies. Fourteen of these (29%) were maximally inhibited by a higher spatial frequency, four (8%) by a lower spatial frequency. Inhibitory interactions in complex cells were never dependent on the relative phase of the two component gratings. Six simple cells (16%) and fourteen complex cells (29%) showed significant facilitation of the response to f by one or more (most often lower) spatial frequencies. This enhanced response was greater than the sum of the responses to each component alone, was usually broadly tuned for spatial frequency, and did not depend on the relative phase of the two components. It thus differs from the increased response sometimes seen in a phase-dependent interaction. Some of the observed spatial-frequency-specific interactions are incompatible with either a strictly hierarchical model of cortical architecture or a simple linear filter model of visual cortical processing. The asymmetry of inhibition suggests that it subserves some function other than (or in addition to) the narrowing of spatial frequency tuning functions.


Herpes zoster and diabetes mellitus: an epidemiological investigation.
Five hundred and ninety Rochester, Minnesota, residents were initially diagnosed with herpes zoster in the period 1945-59. Fifteen had diabetes mellitus before the onset of herpes. The expected number was 15.7. The entire herpes zoster cohort was followed subsequently for nearly 9400 person-years and 33 new cases of diabetes mellitus developed while the expected number was 30.6. The clinical spectrum of herpes zoster in individuals with diabetes mellitus was not different from that of zoster patients from the general population. We conclude that herpes zoster is not a risk factor for diabetes mellitus and that diabetes mellitus is not a risk factor for herpes zoster.


Surface markers for locating the pulleys and flexor tendon anatomy in the palm and fingers with reference to minimally invasive incisions.
Palm and finger pulley anatomy has been well described in relation to osseous structures. The goal of this study was to describe skin surface markers that locate the underlying flexor tendon and pulley system. We describe the anatomic detail of these structures and provide a guide for the surgeon for making small incisions. Using this approach, extensile exposure can be avoided, and the integrity of the complex pulley system is maintained. We dissected 12 palms and 48 fingers in 12 cadaver hands. We marked the palm and finger creases with methylene blue before dissection. We removed palm skin, finger skin, and subcutaneous tissue over the flexor tendon sheath and retained a 2-mm strip of each skin crease in its native position. We divided the palm and palmar surface of the fingers into 4 distinct zones and measured the location of the proximal and distal extent of each pulley and the tendon anatomy relative to the proximal and distal skin crease. We documented the location of the proximal and distal extent of the annular and cruciate pulleys as well as the decussation of the flexor digitorum superficialis (FDS) tendon and Camper chiasm. The results allow us to establish a relationship between the skin creases and underlying anatomy by dividing the palm and finger into 4 zones. In zone A, in the palm, the A2 pulley is located in the distal third and the FDS decussation is at the proximal extent of the A2 pulley. Zone B is in the proximal phalanx and A2 lies in the proximal third of this zone, whereas the Camper chiasm lies in the middle third. Zone C is in the middle phalanx and A4 and the insertion of FDS lie in the middle third of this zone. Zone D lies in the distal phalanx and the flexor digitorum profundus tendon inserts into the middle third of this zone. Skin creases can be used as surface markers to accurately locate the underlying pulley and tendon system and plan for limited incisions. These anatomic descriptions can aid surgeons in preoperative planning and may also help minimize the required exposure for flexor tendon repair and other surgery in the fingers and palm.


Assessment of an in vitro model of lung epithelial cell stress responses.
The ability of cells to adapt and survive environmental and physiological stress relies on activation of cellular stress responses. These include anti-oxidant, inflammatory and apoptotic responses. These cellular responses are mediated by cell signalling pathways, including those controlled by the transcription factors Nrf2 (antioxidant response) and NF-?ß (inflammatory response). As part of a suite of in vitro models for the comparison of different nicotine delivery products, an in vitro lung cell stress response model has been developed. Human bronchial epithelial cells were exposed to positive controls or cigarette smoke aqueous extracts (CSEaq) from 3R4F and 1R5F reference cigarettes for 4hours. Cellular responses were then measured as oxidative, pro-inflammatory, apoptotic and necrotic endpoints. Cellular oxidative stress was characterised by measurement of the intracellular glutathione ratio, intracellular ROS production and activation of the Nrf2-controlled Anti-oxidative Response Elements (ARE). The inflammatory response of the cells was determined through quantification of secreted cytokines, IL-1a, IL-6 and IL-8. Apoptotic and necrotic responses were characterised by measurements of Caspase 3/7 activity and live-cell protease activity. Stably transfected luciferase reporter cell lines were utilised to quantify the transcriptional control of anti-oxidant and inflammatory pathways. All cell stress response endpoints were activated by exposure to positive controls or CSEaq. The observed concentration-dependent lowering of the glutathione ratio and increase in intracellular ROS generation corresponded with an increase in Nrf2 transcriptional activation of the ARE. It has been demonstrated that this model was able to distinguish between CSEaq from the two different reference cigarettes. We propose that this model may be suitably sensitive for biological comparisons of cigarettes against different nicotine delivery products.


Estrous cycle modification of rat uterine DNA alkylation by N-methyl-N-nitrosourea.
The present study was designed to determine whether the stage of the estrous cycle at the time of N-nitroso-N-methylurea (NMU) presentation altered DNA adduct formation and repair in the rat uterus. In uterus the rate of O6-methylguanine (O6-meGua) and 7-methylguanine (7-meGua) formation and the total yield of adducts was estrous cycle dependent. Uterine DNA from rats injected with NMU on diestrus formed O6-meGua and 7-meGua more rapidly and had significantly higher adduct levels than those rats injected on proestrus or estrus. Repair of O6-meGua and 7-meGua was also significantly faster between 1 and 24 h post-NMU in uterine DNA isolated from rats injected on diestrus compared to those injected on proestrus or estrus.


Consistency of prostate cancer grading results in screened populations across Europe.
To assess the consistency of grading outcome among seven of eight participating centres of the European Randomised Screening Program of Prostate Cancer (ERSPC), a multicentre randomized trial intended to detect a difference in prostate cancer-related mortality between screened participants and a control group. Currently, tumour stage and grade in prostatectomy specimens represent the most predictive variables for biological behaviour. In prostate needle biopsies the tumour grade is a strong factor for deciding therapy. Within the ERSPC all prostate cancers detected in needle biopsies were graded according to the Gleason score system. Gleason scores were compressed in three categories of < or = 6, 7 and 8-10. Data for grading outcome were obtained from the databases from seven individual centres; in one centre the slide sets with cancer were separately reviewed. Combining the data of seven ERSPC centres 66% of cancers detected in the screening arm were Gleason score < or = 6 and 92% were < or = 7. Gleason score 8-10 cancers varied from 2 to 11%. This variation in Gleason scores may be attributed to differences in the population characteristics and biopsy indications. These data indicate that in the seven ERSPC centres most screen-detected cancers have favourable characteristics on biopsy. Men with these cancers are amenable for treatment with curative intent. The observed differences in Gleason score distribution in different centres may partly be attributed to geographical differences and differences in the age range of the screened populations.


Transcriptomic points of departure calculated from human intestinal cells exposed to dietary nanoparticles.
Use of nanoparticles (NPs) in the food industry raises dietary health concerns. Assessing dietary NPs remains challenged due the vast number of products and the resource-intensive nature of toxicity testing. Advancements in high-throughput transcriptomics, coupled with benchmark dose (BMD) analysis are poised to modernize chemical safety assessments. The study objective was to derive transcriptomic point of departure (tPOD) values for common dietary NPs through dose-response analysis of 3'RNA-sequencing data. Two intestinal cell lines (Caco-2, HIEC-6) were exposed to 9 forms of Ag, SiO2, and TiO2, and expression of L1000 landmark genes was characterized. In Caco-2 cells, tPODmode concentrations were 0.4-0.6, 21-32, and 17-59 ppm for NPs of Ag, SiO2, and TiO2, respectively; in HIEC-6 cells, the respective tPOD values were 6-7, 7-9, and 3-13 ppm. Pathway BMDs across cases identified, for example, osteoclast and Th1/Th2 cell differentiation, and cell cycle, signaling, and senescence pathways. In all cases, the tPOD and pathway BMD values were lower than concentrations associated with cellular changes (e.g., generation of reactive oxygen species and proinflammatory cytokines, and cytotoxicity). These results demonstrate that transcriptomics dose-response analysis using in vitro models can help to increase understanding of a NP's mechanisms of action and derive quantitative information for dietary risk assessment.


Factors impacting stem cell mobilization failure rate and efficiency in multiple myeloma in the era of novel therapies: experience at Memorial Sloan Kettering Cancer Center.
Thalidomide, lenalidomide and bortezomib have increasingly been incorporated in first-line induction therapies for multiple myeloma. Concerns regarding the impact of these agents, especially lenalidomide, on stem cell mobilization prompted us to re-evaluate the risk factors that impact mobilization, including exposure to novel induction regimens. Among 317 patients who proceeded to stem cell collection after induction therapy between 2000 and 2009, the rate of mobilization failure, defined as the inability to collect 5 × 10(6) CD34+ cells/kg following the first collection attempt, was 13%. By multivariate analysis, independent risk factors associated with mobilization failure included older age (P=0.04), lower platelet count (P=0.002) and use of single-agent G-CSF for mobilization (P<0.0001). When considering for outcome measurement stem cell collection efficiency measured by the number of CD34+ cells yielded per pheresis performed during first collection attempt, lower platelet count, use of single-agent G-CSF and older age were also associated with lower efficiency. In this population mobilized mostly with cyclophosphamide and G-CSF, the use of lenalidomide during induction was not associated with a lower stem cell collection efficiency by multivariate analysis. The data support the current International Multiple Myeloma Working Group guidelines recommending the use of cyclophosphamide and G-CSF based mobilization for patients previously exposed to lenalidomide.


Effect of peracetic acid solution on a nitrifying culture: Kinetics, inhibition, cellular and transcriptional responses.
Peracetic acid (PAA) has been widely used as a disinfectant in many industries. However, information related to the potential inhibitory effect of PAA solutions (PAA and H2O2) on biological wastewater treatment processes is very limited. The work reported here assessed the effect of PAA and H2O2 solutions on nitrification kinetics and inhibition, cellular level responses and gene expression of a suspended-growth nitrifying culture. The initial ammonia removal and nitrate production rates significantly decreased at 1/0.14 to 3/0.42 mg/L PAA/H2O2. H2O2 up to 3 mg/L did not impact nitrification, cell viability or related respiratory activities; thus, the impact of the PAA solution is attributed to PAA alone or in some combination with H2O2. Nitrification inhibition by PAA was predominantly related to enzyme inhibition, rather than to loss of cell viability and/or cell lysis. PAA and H2O2 negatively affected Nitrosomonas but resulted in Nitrosospira enrichment. Most nitrogen metabolism-related genes (e.g., hydroxylamine oxidoreductase and nitrite oxidoreductase genes) as well as oxidase genes (e.g., cytochrome c oxidase, catalase-peroxidase, and peroxidase genes) were upregulated in PAA- and H2O2-amended cultures. Major ATPase genes were downregulated while ATP synthase genes upregulated under the effect of PAA and/or H2O2. Upregulation of ATP-dependent protease genes indicates protein damage predominantly caused by PAA rather than H2O2. The transcriptional level of genes related to cell division and DNA repair did not show a particular pattern; thus, cell division functionality and DNA integrity were not significantly affected by PAA or H2O2. The results of this study have significant implications in the design and operation of effective biological nitrogen removal systems for the treatment of PAA-bearing wastewater.


Integrating Principles of Safety Culture and Just Culture Into Nursing Homes: Lessons From the Pandemic.
Decades of concerns about the quality of care provided by nursing homes have led state and federal agencies to create layers of regulations and penalties. As such, regulatory efforts to improve nursing home care have largely focused on the identification of deficiencies and assignment of sanctions. The current regulatory strategy often places nursing home teams and government agencies at odds, hindering their ability to build a culture of safety in nursing homes that is foundational to health care quality. Imbuing safety culture into nursing homes will require nursing homes and regulatory agencies to acknowledge the high-risk nature of post-acute and long-term care settings, embrace just culture, and engage nursing home staff and stakeholders in actions that are supported by evidence-based best practices. The response to the COVID-19 pandemic prompted some of these actions, leading to changes in nursing survey and certification processes as well as deployment of strike teams to support nursing homes in crisis. These actions, coupled with investments in public health that include funds earmarked for nursing homes, could become the initial phases of an intentional renovation of the existing regulatory oversight from one that is largely punitive to one that is rooted in safety culture and proactively designed to achieve meaningful and sustained improvements in the quality of care and life for nursing home residents.


[Effect of estrone on rat uterine contraction induced by prostaglandin (author's transl)].
Influence of estrone on uterine contraction and increase of internal pressure of uterus induced by PG were studied in the rat. The sensitivity of the uterus to PG was increased after estrone injection, the maximum effect being observed 72 hours after the administration. Regarding uterine contraction and increase of internal pressure induced by PGE2 or PGF2alpha, the amplitude was enlarged but the frequency was decreased with estrone injection. Contraction and increase of internal pressure induced by PG were well correlated in the rat uterus treated with estrone. Progesterone inhibited the stimulatory action of estrone on uterine contraction induced by PG. These results suggest that estrone may play an important role in action of PG in rat uterus.


Predicted normocapnea in infants and children using the Bain circuit with controlled ventilation.
We have constructed a nomogram for fresh gas flow (VFG) and minute ventilation (VE) for paediatric anaesthesia during controlled ventilation using the Bain coaxial Mapleson D circuit. VFG was based upon the assumption of a high fresh gas utilization because of a low VFG/VE ratio (0.67) and known figures of carbon dioxide elimination. The formulas VFG = 27.8 x VCO2 and VE = 1.5 x VFG were used to calculate the necessary flows to generate normocapnea. The nomogram was evaluated in 59 children (6-62 kg, age 5 months-14 years). PaCO2 (mean +/- s.d.) was 5.0 +/- 0.5 kPa (38 +/- 4 mmHg) with a total range of 3.9-6.3 kPa (29-47 mmHg). Ninety percent of the children had a PaCO2 of 5.7 kPa (43 mmHg) or lower. There was no correlation between body weight and PaCO2. Hence, there was no difference in mean values between children below or above a body weight of 20 kg.


Prospective Evaluation of Sleep Disturbances After Total Knee Arthroplasty.
Sleep disturbance after total knee arthroplasty (TKA) has not been studied 6 months after surgery. A prospective study was conducted on 34 primary, unilateral TKA patients preoperatively until 6 months postoperatively. Sleep quality was measured using the Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale. Pain was measured on a visual analog scale. Sleep quality worsened from baseline during the first 6 weeks postoperatively (P = .03), but improved at 3 and 6 months (P = .003). Pain scores decreased from baseline over all time points, and there was no correlation between sleep quality and pain. The Epworth Sleepiness Scale did not change over time. This study can be used to counsel TKA patients to expect initial sleep disturbances that improve by 3 months.


Mechanisms of hyperpolarizing effect of GABA on resting potential of the Lumbricus terrestris muscular wall somatic cells.
GABA, baclofen, isoguvacine increase, and cis-4-aminocrotonic acid does not modify resting membrane potential of muscle cells. Bicuculline, phaclofen, N-ethylmaleimide, chlorpromazine, verapamil, and removal of Ca2+ from bathing solution abolished the effect of baclofen, while U73122 and D609 were ineffective in this respect. The authors conclude that the Lumbricus terrestris muscle cells contain GABAergic structures similar to a- and b-receptors. Activation of GABA receptors induced Cl- inward current and Ca2+ entry with subsequent activation of calmodulin-like proteins, which causes membrane hyperpolarization by increasing the effect of "pumping potential" on resting membrane potential.


Serum prolactin levels among outpatients with major depressive disorder during the acute phase of treatment with fluoxetine.
To determine changes in serum prolactin levels in outpatients with DSM-IV-diagnosed major depressive disorder (MDD) following a 12-week open-label trial of fluoxetine. 87 outpatients enrolled in the trial had serum prolactin levels determined at baseline and during their final visit (week 12 or discontinuation visit). In addition, serum testosterone levels were measured in 44 of the 46 men during these 2 visits. Hyperprolactinemia was defined as a serum prolactin level greater than 16.5 ng/mL or 18.9 ng/mL for men and women, respectively. The study was conducted from September 1997 to March 2002. Of 80 patients with normal prolactin levels at baseline, 10 (12.5%) developed hyper-prolactinemia following fluoxetine treatment. Specifically, 2 (4.5%) of 44 men and 8 (22.2%) of 36 women with normal prolactin levels at baseline developed hyperprolactinemia following treatment with fluoxetine (p = .0174 for between-gender difference). In addition, there was a significant increase in mean +/- SD serum prolactin levels following treatment with fluoxetine in all patients with normal baseline prolactin levels (6.4 +/- 3.4 to 10.0 +/- 7.0 ng/mL, p = .002). There were no significant changes from baseline in testosterone levels in men following fluoxetine treatment (448.4 +/- 139.6 to 439.5 +/- 142.1 ng/dL, p > .05; normal above 245 ng/dL), while none of the 44 men developed low testosterone levels following fluoxetine treatment. 4.5% of men and 22.2% of women with MDD developed new onset hyper-prolactinemia following fluoxetine treatment.


Substance P stimulation of amylase release by isolated parotid cells and inhibition of substance P induction of salivation by vasoactive peptides.
Substance P stimulation of salivation in rats has been studied as has its in vitro enhancement of amylase release by isolated parotid cells. The extent of the stimulation on amylase release by isolated parotid cells was dependent upon the concentration of substance P, with the minimum effective concentration being 1 nM. The substance P effect was detectable within 1 min after incubation and lasted for at least 50 min. Substance P stimulation was demonstrable at 25--37 degrees C but not at 0 degrees C. Adrenocorticotropic hormone (ACTH), thyrotropin-releasing hormone (TRH), vasopressin and neurotensin had no effect on amylase release. These results suggest that substance P may act directly on the parotid cells. Examination of the salivary-stimulating activity of fragments of substance P showed that the C-terminal octapeptide and (pyroglutamyl)hexapeptide were active, although less potent than substance P, whereas its free acid, C-terminal tetra- and tri-peptides were inactive. Vasopressin, angiotensin II and neurotensin could inhibit substance P induced salivation, whereas TRH, ACTH and somatostatin had no effect. Amylase activity per unit volume of saliva was not changed by the injection of vasopressin, angiotensin II or neurotensin. These vasoactive peptides did not affect substance P stimulation of amylase release by isolated parotid cells. The results indicate that vasopressin, angiotensin II and neurotensin inhibit the action of substance P on salivation at sites other than the parotid cells.


The use of optical coherence tomography in the evaluation of patients with bipolar disorder.
Bipolar disorder (BD) is a mental disorder characterised by episodes of extremal mood changes. In recent years, some researchers found neurodegeneration in patients with BD using Magnetic Resonance Imaging. Evaluation of the optic nerve and the retinal layers using optical coherence tomography (OCT) has proved to be a useful, non-invasive tool for diagnosis and monitoring of neurodegenerative diseases. Accordingly, a decrease in the retinal nerve fibre layer and the ganglion cell complex measured by OCT was found in patients with BD in different studies, suggesting that BD is a neurodegenerative process in addition to a psychiatric disorder. Therefore, the neuro-ophthalmological evaluation of these patients could be used as a marker for diagnosis of this disease. This work analyses literature on retinal degeneration in bipolar disorder patients, and evaluates the ability of OCT devices in the detection of neuronal degeneration affecting the different retinal layers in these patients, and its possible role in the diagnosis and monitoring of the disease.


Mindful staff increase learning and reduce aggression in adults with developmental disabilities.
Aggression by individuals with developmental disabilities may threaten their community placement. In a multiple baseline design across group homes, we provided group home staff with behavioral training and later with mindfulness training to assess the impact on aggressive behaviors and the number of learning objectives mastered by individuals in their care. We also assessed other outcomes including activities engaged in by the individuals, use of restraint by staff, and measures of satisfaction. The effect of varying staff-resident ratios was evaluated on all measures. When compared to baseline, the number of staff interventions for aggression showed some reduction following behavioral training, but decreased substantially only following mindfulness training. There was also some increase in the number of learning objectives mastered by the individuals following behavioral training, but greater and more consistent increases were obtained only after mindfulness training. Improvements also occurred on the other measures assessed after behavioral training, but these were always greater and more consistent following mindfulness training. In addition, consistent gains followed behavioral training only with a high staff-resident ratio whereas the larger gains after mindfulness training occurred with both medium and low staff-resident ratios. Our results suggest that the addition of mindfulness training considerably enhanced the ability of the group home staff to effectively manage the aggressive behavior and learning of the individuals.


Temporal changes of incomplete stent apposition during early phase after everolimus-eluting stent implantation: serial optical coherence tomography analyses at 2-week and 4-month.
The healing process of acute incomplete stent apposition (ISA) in the early phase after stent implantation has not been well understood. We evaluated the temporal changes of ISA during the early phase after everolimus-eluting stent (EES) implantation using serial optical coherence tomography (OCT) analyses. Serial OCT examinations were performed immediately post-stenting and 2-week and 4-month after EES implantation for patients with ST-segment elevation myocardial infarction. At the most proximal cross-section of the implanted stent, the prevalence of ISA and maximum ISA distance were serially evaluated. In 45 patients with ST-segment elevation myocardial infarction, serial OCT analyses at 2-week and 4-month were performed. The prevalence of ISA gradually decreased over time, being 53.3% at baseline, 37.8% at 2-week follow-up, and 11.1% at 4-month follow-up (P < 0.001). The maximum ISA distance also decreased over time (P < 0.001). A receiver-operating curve analysis found that the optimal cut-off values of the baseline ISA distance for predicting persistent ISA at 2-week follow-up and 4-month follow-up were > 140 µm and > 215 µm, respectively. The baseline ISA distance was closely associated with the healing of ISA in the early phase after EES implantation. Maintaining the minimum ISA distance at post-stenting facilitates early phase healing of acute ISA.


Ex vivo model for pre-clinical evaluation of dialyzers containing new membranes.
The ex vivo model which reflects hemodialysis modulating factors during the first twenty minutes of blood membrane interaction, is applicable as a pre-clinical test for new membranes. The biocompatibility of a new cellulosic membrane (MC) proved to be superior to regenerated cellulose and comparable to synthetic membranes such as PAN regarding complement activation.


Clinical and radiological outcome of Mason-Johnston types III and IV radial head fractures treated by an on-table reconstruction.
Only few methods treating comminuted radial head fractures have been established providing sufficient joint reconstruction, restoring radial length and enabling early joint mobilization. When an anatomical reconstruction using open reduction and internal fixation is not possible, radial head resection or primary arthroplasty is often conducted. An "Ex situ/on-table" reconstruction is widely disregarded but can be an option. The purpose of this study was to evaluate the functional and radiological outcome of comminuted radial head fractures treated with an "on-table" reconstruction and internal fixation using a low profile plate. Fourteen patients who sustained a radial head fracture (9 Mason-Johnston type III and 5 Mason-Johnston type IV) and were treated with an "on-table" reconstruction between 2010 and 2020 were evaluated retrospectively. The patients mean age was 41.3 years (range 21-69). The clinical evaluation included active range of motion, grip strength, pain level and elbow stability. The functional outcome was assessed using the Disability of Arm, Shoulder and the Hand (DASH) score, Mayo Elbow Performance Index (MEPI), Broberg and Morrey score. The radiological examination included a.p. and lateral views of the injured elbow to evaluate nonunions, loss of reduction, joint alignment, avascular radial head necrosis, heterotopic ossifications and posttraumatic osteoarthritis. The inclusion rate was 74% with a mean follow-up of 50 months (range 16-128). The mean elbow flexion of the injured side was 126° (range110-145°) with an average extension loss of 8° (range 0-40°). Pronation was 65° (15-90°) and supination 66° (5-90°). The mean MEPI was 87 points (range 45-100). The mean DASH score was 13 points (range 1-88). According to the Broberg and Morrey functional scoring system, the average score was 92 points (range 88-100). Complete bone union was achieved in 9 cases, partial union in 4 cases and nonunion in one case. There were no signs of avascular necrosis of the radial head. Signs of post-traumatic osteoarthritis were seen in 11 cases. Five patients needed an implant removal due to a radio-ulnar impingement and one patient a revision surgery due to the nonunion and implant breakage. An on-table (ex situ) reconstruction of the radial head is a reliable option with a good clinical outcome and low complication rate in the surgical treatment of comminuted radial head fractures. It can restore joint alignment and maintain radial length. The risk for avascular necrosis is neglectable, and the bone healing rate is high.


Cardiac ultrastructure in primary restrictive cardiomyopathy.
A five-year clinical follow-up and the results of myocardial biopsies are described in a patient with primary restrictive cardiomyopathy. Histologic examination of a right ventricular endomyocardial biopsy taken early in the course of the illness was not contributory. Histologic examination of a left ventricular endomyocardial biopsy five years later showed hypertrophy and disarray of myocytes, thickening of the endocardium, and interstitial fibrosis. Connective tissue was compact and regularly oriented in the endocardium, but tangled and irregularly oriented in the interstitium. It is concluded that the irregular network of collagen fibrils and elastic fibers limits diastolic relaxation and prevents ventricular dilatation; that the coexisting hypertrophy results from an attempt to maintain normal pump function; and that the myocyte disarray is a consequence of abnormal mechanical forces generated under conditions of severe fibrosis.


Import of a mitochondrial presequence into P. denitrificans. Insight into the evolution of protein transport.
According to the endosymbiont hypothesis, mitochondria are descended from ancient aerobic bacteria that were engulfed by protoeukaryotic cells. Experiments described here show that a synthetic peptide corresponding to a yeast mitochondrial targeting sequence can be imported into Paracoccus denitrificans, a soil bacterium thought to be closely related to the protomitochondrion. The import is very similar to that observed with isolated yeast mitochondria. The results suggest that the protomitochondrion may have been inherently able to translocate mitochondrial presequences. This ability may partly explain the development of the protein import process during the evolution of the mitochondrion.


Automated differential diagnosis method for iron deficiency anemia and beta thalassemia trait based on iterative Chi2 feature selector.
The differential diagnosis of anemia is an important issue for hematology laboratories. We aimed at investigating the performance of a powerful computer-based model to aid diagnosis. Our work presents a new feature selection-based automated disease diagnosis model. To create a testbed, a new corpus is collected retrospectively. Our data sets contain beta thalassemia trait, iron deficiency anemia, and healthy groups. Our presented automated ailment classification model consists iterative chi2 (IChi2) feature selection and classification phases. The used data set includes 25 features, and IChi2 selects the 20 most valuable of them. These are forwarded to 24 traditional classifiers. In this work, two data sets have been used to test our proposal. In the classification phase of this model, 24 shallow classifiers have been used and the best accurate classifiers are Medium Gaussian Support Vector Machine (MGSVM) and Coarse Tree (CT) for the first and second data sets, respectively. These classifiers have been attained 97.48% and 99.73% classification accuracies using the first and second data sets, consecutively. These results are calculated using 10-fold cross-validation. Moreover, hold-out validation has been used in this work, and the results are given in the experiments. Our results denoted the success of IChi2-based classification model for diagnosis on the laboratory data set. We have found a new and robust model to differentiate iron deficiency anemia and beta thalassemia trait. This model may be beneficial for rational laboratory use.


Experimental data manipulations to assess performance of hyperspectral classification models of crop seeds and other objects.
Optical sensing solutions are being developed and adopted to classify a wide range of biological objects, including crop seeds. Performance assessment of optical classification models remains both a priority and a challenge. As training data, we acquired hyperspectral imaging data from 3646 individual tomato seeds (germination yes/no) from two tomato varieties. We performed three experimental data manipulations: (1) Object assignment error: effect of individual object in the training data being assigned to the wrong class. (2) Spectral repeatability: effect of introducing known ranges (0-10%) of stochastic noise to individual reflectance values. (3) Size of training data set: effect of reducing numbers of observations in training data. Effects of each of these experimental data manipulations were characterized and quantified based on classifications with two functions [linear discriminant analysis (LDA) and support vector machine (SVM)]. For both classification functions, accuracy decreased linearly in response to introduction of object assignment error and to experimental reduction of spectral repeatability. We also demonstrated that experimental reduction of training data by 20% had negligible effect on classification accuracy. LDA and SVM classification algorithms were applied to independent validation seed samples. LDA-based classifications predicted seed germination with RMSE = 10.56 (variety 1) and 26.15 (variety 2), and SVM-based classifications predicted seed germination with RMSE = 10.44 (variety 1) and 12.58 (variety 2). We believe this study represents the first, in which optical seed classification included both a thorough performance evaluation of two separate classification functions based on experimental data manipulations, and application of classification models to validation seed samples not included in training data. Proposed experimental data manipulations are discussed in broader contexts and general relevance, and they are suggested as methods for in-depth performance assessments of optical classification models.


The effects of apheresis, storage time, and leukofiltration on microparticle formation in apheresis platelet products.
Although platelet microparticles (PMPs) were the most abundant micoparticles (MPs) in platelet (PLT) products, other MPs and their parental cells can also be brought into the plasma during PLT apheresis. However, the effects of PLT apheresis, storage time, and leukofiltration on these MPs remain largely unclear. Apheresis PLTs with or without leukofiltration were stored in 22 ± 2 °C for 5 days. PLT-poor plasma (PPP) was generated by centrifugation of donor blood or PLT products at 2500 × g for 15 minutes on the point day. PPP was labeled with CD41a (PLT-derived MP, PMP), CD235 (red blood cell-derived MP, RMP), CD45 (leukocyte-derived MP, LMP), CD14 (monocyte-derived MP, MMP), and CD144 (endothelial cell-derived MP, EMP), and then measured by flow cytometry. Higher-level TMPs (total microparticles) and PMPs, but lower-level RMPs, LMPs, and MMPs were detected in fresh PLTs on the day of collection compared with those before collection. During storage, TMP, PMP, and RMP counts were significantly higher on Day 3 and Day 5, but MMP and LMP counts were only marginally higher on Day 3 in PLT supernatants. There were no significant differences in MP levels in PLTs with or without leukofiltration. MP formation was affected by the apheresis procedure. RMPs, LMPs and MMPs were lower after PLT apheresis. During storage, TMPs, PMPs, RMPs, LMPs, and MMPs were found to be higher in PLT supernatants. Leukofiltration exerted no significant effect on all MPs in PLT products.


Assessment of lung volume and alveolar pressure during combined high-frequency jet ventilation in a child with adult respiratory distress syndrome.
Lung volume and alveolar pressure were assessed using inductance plethysmography, airway occlusion and pneumotachography in a child with severe adult respiratory distress syndrome during both conventional mechanical and combined high-frequency ventilation (HFJV). The results suggest that improved oxygenation during combined HFJV is associated with higher end-expiratory lung volume and lower peak and mean lung volume and alveolar pressure.


Developmental aspects of renal beta-amino acid transport I. Ontogeny of taurine reabsorption and accumulation in rat renal cortex.
Newborn Sprague-Dawley rat pups were found to have reduced net tubular reclamation of the beta-amino acid taurine in vivo. The reabsorption of this compound increased between the 2nd and 4th week of life and the excreted taurine fell despite a rise in glomerular filtration rate indicative of increased transport with maturation. Kidney cortex in vivo accumulated taurine from plasma against a large chemical gradient. Newborn cortex slices in vitro accumulated taurine to higher levels at steady state at less than 0.4 mM, but uptake was less efficient at higher taurine concentrations. Further metabolism of taurine by cortex slices was not found at any age. Accumulation in adult and newborn cortex was greatest at 10-15 mEa/liter K in the external medium. Slices from younger animals had slightly higher pH optima for uptake and temperature elevation increases uptake more in neonatal than in adult kidney.


Subjective visual perceptions during vitreoretinal surgery under local anaesthesia.
To evaluate the visual experiences of patients during vitreoretinal surgery under local anaesthesia (LA). Prospective questionnaire survey of 80 patients within 30 min of completion of vitreoretinal surgery under LA. Preoperative visual acuity, surgical procedure and its duration, efficacy of the local block, as well as intraoperative perceptions of flashes, colours, movements, and seeing instruments were documented. A sub-Tenon's block was performed in 62/80 (77.5%) and a peribulbar block in the remainder. Overall, 72 (90%) of patients perceived light at some stage during their surgery. Of these, 51 (70.83%) observed movements, 45 (62.5%) saw colours, 38 (52.77%) saw instruments, and 24 (33.33%) saw flashes. The commonest observations were colourful swirls, black pipes, and the colour red. Most patients found these experiences pleasant or bearable; two found them frightening, and four would like to have been warned preoperatively about them. Preoperative visual acuity, diagnosis, gender of the patient, degree of akinesia, and the duration of surgery did not associate with visual perceptions. Logistic regression analysis showed that younger people were more likely to experience flashing lights (P=0.03) and to see instruments (P=0.04), patients having a sub-Tenon's block to perceive light (P=0.005), and those who did not receive awake sedation were more likely to see instruments (P=0.04). Visual experiences are common during vitreoretinal surgery undertaken under LA. Where appropriate, patients should be forewarned about these experiences and reassured that they are not normally frightening.


The effects of initial movement dynamics on human responses to postural perturbations.
Falls are a major cause of injury, and often occur while turning, reaching, or bending. Yet, we have little understanding of how an ongoing feet-in place activity at the onset of imbalance, and its associated cognitive and biomechanical demands, influence our ability to recover balance. In the current study, we used an ankle-rocking paradigm to determine how the nature of the baseline task influences the balance recovery response to a backward support surface translation. Fourteen participants were instructed to "recover balance without stepping" and were perturbed at vertical while standing quietly ("S"), while ankle rocking and moving forward ("A_f"), or while ankle rocking and moving backward ("A_b"). The results showed that changes in rocking velocity at the time of the perturbation elicited changes in the incidence of stepping, magnitude of trunk angular displacements (p<.01), and the onset latencies of distal muscles (gastrocnemius and soleus, both p<.01) used to recover balance. In addition, plots of onset latencies across all muscles showed that onset latencies appeared to occur earlier in many muscles when participants held a static position compared to when they performed a dynamic task at the onset of the perturbation. The results suggest that muscle activities used to recover balance are tailored to the nature of the perturbation and the ongoing task, and that onset latencies are later when participants are performing a dynamic as opposed to static task at the time of a perturbation. These findings support previous research suggesting that automatic postural responses are highly adaptable to environmental, situational, and task demands.


Prenatal diagnosis of L1 cell adhesion molecule mutations. Capabilities and limitations.
Discuss the capability for and limitations of prenatal detection of L1 cell adhesion molecule (L1CAM) mutations. Haplotype analysis by PCR and PAGE. Mutation detection by SSCP, followed by dideoxy sequencing. Confirmation of sequencing results with PCR and NcoI digestion. A 1-bp deletion was found in exon 2 of L1CAM in all affected males and obligate carriers in the pedigree. Prenatal detection is now possible for subsequent pregnancies. In a large gene with widespread mutations such as L1CAM, a mutation must be detected in another family member before direct prenatal mutation testing can be done within the required timeframe. If the proper family members are available, haplotyping offers a fast but indirect test with several limitations.


C. elegans as a model to study mitochondrial biology and disease.
Mitochondria perform a myriad of essential functions that ensure organismal homeostasis, including maintaining bioenergetic capacity, sensing and signalling the presence of pathogenic threats, and determining cell fate. Their function is highly dependent on mitochondrial quality control and the appropriate regulation of mitochondrial size, shape, and distribution during an entire lifetime, as well as their inheritance across generations. The roundworm Caenorhabditis elegans has emerged as an ideal model organism through which to study mitochondria. The remarkable conservation of mitochondrial biology has allowed C. elegans researchers to investigate complex processes that are challenging to study in higher organisms. In this review, we explore the key recent contributions of C. elegans to mitochondrial biology through the lens of mitochondrial dynamics, organellar removal, and mitochondrial inheritance, as well as their involvement in immune responses, various types of stress, and transgenerational signalling.


Malus-metasurface-assisted polarization multiplexing.
Polarization optics plays a pivotal role in diffractive, refractive, and emerging flat optics, and has been widely employed in contemporary optical industries and daily life. Advanced polarization manipulation leads to robust control of the polarization direction of light. Nevertheless, polarization control has been studied largely independent of the phase or intensity of light. Here, we propose and experimentally validate a Malus-metasurface-assisted paradigm to enable simultaneous and independent control of the intensity and phase properties of light simply by polarization modulation. The orientation degeneracy of the classical Malus's law implies a new degree of freedom and enables us to establish a one-to-many mapping strategy for designing anisotropic plasmonic nanostructures to engineer the Pancharatnam-Berry phase profile, while keeping the continuous intensity modulation unchanged. The proposed Malus metadevice can thus generate a near-field greyscale pattern, and project an independent far-field holographic image using an ultrathin and single-sized metasurface. This concept opens up distinct dimensions for conventional polarization optics, which allows one to merge the functionality of phase manipulation into an amplitude-manipulation-assisted optical component to form a multifunctional nano-optical device without increasing the complexity of the nanostructures. It can empower advanced applications in information multiplexing and encryption, anti-counterfeiting, dual-channel display for virtual/augmented reality, and many other related fields.


Impact of the lockdown by the COVID-19 pandemic on suicidal trend in the Colombian Coffee Region.
Suicide is considered a Public Health issue. In 2019 the Colombian suicide rate was 5.8 per-100.000 inhabitant. Likewise, the Colombian Coffee Region has doubled the national average on these rates. On the other hand, the Pandemic COVID 19 socio-economic consequences are aggravating the risk factors that we've known about suicide. To evaluate the suicidal trend in the population of the Colombian Coffee Region during the COVID-19 pandemic and compare it with a non-pandemic period. The data were taken from the National Institute of Legal Medicine and Forensic Science for the suicidal events during the 2016-2020 period in the Colombian Coffee Region, and the Montecarlo Regression was applied using the JoinPoint Regression Program. We found 1022 cases, most of them were men. The mean age was 34 years. The most used method was hanging in both sexes. Half of them had at least a high school degree. Half of the suicides were committed by single people. One-third of the cases had a previous mental illness. There are significant differences in the suicidal trend between the lockdown period and the non-lockdown period with a P value < 0.05. We found most suicidal cases between older men and an inversely proportional relationship between education and suicidal rate. Is interesting that the most applied method for suicide for both sexes was hanging. The suicidal trend was increasing until 2020, although in the lockdown we found a decrease. In the post-lockdown period for men was a posterior increase and for women the trend has a continued decrease.


Prokaryotic Genome Expansion Is Facilitated by Phages and Plasmids but Impaired by CRISPR.
Viruses and plasmids can introduce novel DNA into bacterial cells, thereby creating an opportunity for genome expansion; conversely, CRISPR, the prokaryotic adaptive immune system, which targets and eliminates foreign DNAs, may impair genome expansions. Recent studies presented conflicting results over the impact of CRISPR on genome expansion. In this study, we constructed a comprehensive dataset of prokaryotic genomes and identified their associations with viruses and plasmids. We found that genomes associated with viruses and/or plasmids were significantly larger than those without, indicating that both viruses and plasmids contribute to genome expansion. Genomes were increasingly larger with increasing numbers of associated viruses or plasmids. Conversely, genomes with CRISPR systems were significantly smaller than those without, indicating that CRISPR has a negative impact on genome size. These results confirmed that on evolutionary timescales, viruses and plasmids facilitate genome expansion, while CRISPR impairs such a process in prokaryotes. Furthermore, our results also revealed that CRISPR systems show a preference for targeting viruses over plasmids.


Neuropeptide F regulates feeding via the juvenile hormone pathway in Ostrinia furnacalis larvae.
Feeding by pests is one of the most important reasons for reductions in agricultural crop yield. This study aimed to reveal how juvenile hormone (JH) participates in larval feeding regulation of the Asian corn borer Ostrinia furnacalis. Larvae of O. furnacalis exhibit a daily circadian feeding rhythm, with a peak at ZT18 and a trough at ZT6 under both photoperiod (LD) and constant dark (DD) conditions, which may be eliminated by application of fenoxycarb, a JH active analogue. JH negatively regulates larval feeding as a downstream factor of neuropeptide F (NPF), in which knocking down JH increases larval feeding amount along with body weight and length. The production of JH in the brain-corpora cardiaca-corpora allata (brain-CC-CA) is regulated by brain NPF rather than gut NPF, which was demonstrated in Drosophila larvae through GAL4/UAS genetic analysis. In addition, feeding regulation of JH is closely related to energy homeostasis in the fat body by inhibiting energy storage and promoting degradation. The JH analogue fenoxycarb is an effective pesticide against O. furnacalis, controlling feeding and metabolism. The brain NPF system regulates JH, with functions in food consumption, feeding rhythms, energy homeostasis and body size. This study provides an important basis for understanding the feeding mechanism and potential pest control of O. furnacalis. © 2022 Society of Chemical Industry.


Protocol for designing and preparing gallium particles using cell membrane encapsulation for applications in melanoma cryoablation therapy.
Liquid metals are increasingly applied in drug delivery, in vivo imaging, and biosensing. Herein, we describe a surface modification strategy, where cell membrane is introduced to encapsulate gallium (Ga) particles. We detail preparation steps of Ga microparticles by sonication, followed by Ga microparticles coating with purified tumor cell membranes and morphological assessment using TEM and cryo-TEM. We further describe cell uptake and establishment of tumor-bearing mouse models and steps to assess in vitro cytotoxicity and in vivo antitumor cryotherapy. For complete details on the use and execution of this protocol, please refer to Wang et al. (2022).


Berberine inhibits norepinephrine-induced apoptosis in neonatal rat cardiomyocytes via inhibiting ROS-TNF-α-caspase signaling pathway.
To determine the effect of berberine (Ber) on norepinephrine (NE)-induced apoptosis in neonatal rat cardiomyocytes. The cultured neonatal rat cardiomyocytes were treated with NE in the presence or absence of Ber. The activity of lactate dehydrogenase (LDH) in the culture medium was examined, and apoptosis of cardiomyocytes was assessed by Hoechst 33258, isothiocyanate (FITC)-conjugated annexin-V, and propidine iodide (PI) staining. In addition, the activities of caspases-2 and-3 were measured by a fluorescent assay kit. The level of secreted tumor necrosis factor α (TNF-α) and production of intracellular reactive oxygen species (ROS) were also determined. NE at a concentration of 50 μ mol/L induced an obvious increase in the activity of LDH in the culture medium (P<0.05), which was inhibited by coincubation with 0.5, 1.0, or 2.0 μ mol/L Ber (P<0.05). Ber also significantly attenuated NE-induced apoptosis in a dose-dependent manner (P<0.01). Moreover, Ber at a dose of 2 μ mol/L markedly decreased the ROS and TNF-α productions (P <0.05) and inhibited the activation of caspases-2 and -3 in cardiomyocytes exposed to NE (P<0.05)h. The present study suggested that Ber could reduce NE-induced apoptosis in neonatal rat cardiomyocytes through inhibiting the ROS-TNF-α-caspase signaling pathway.


Insulin binding by normal and neoplastic colon tissue.
Insulin receptors in human colon tumours, normal colon tissue and mesenteric fat removed at surgery have been identified by measuring the binding of labelled insulin to cell membrane preparations. Insulin binding sites were readily detected in all tissues, with mean +/- SD binding site concentrations of 43 +/- 41, 44 +/- 39, and 44 +/- 35fmol/mg membrane protein, and dissociation constants of 0.73 +/- 0.61, 0.66 +/- 0.41, and 0.78 +/- 0.58nM for microsomal plasma membrane preparations of tumour (n = 23) respectively. The specificity of binding of labelled insulin was similar in tumour and normal colon samples. Binding in normal colon preparations was highest in the epithelium (84fmol/mg membrane protein) and lower in lamina propria (19fmol/mg), submucosa (25fmol/mg) and muscle wall (13fmol/mg). Degradation of labelled insulin was similar in tumour and normal colon preparations. Mean receptor levels were not significantly different between microsomal membrane preparations and plasma membranes partially purified on discontinuous sucrose gradients, quantitated against either unit membrane protein or unit 5'-nucleotidase specific activity. There was a significant negative correlation between insulin levels, but no significant relationship was seen between serum insulin and receptor levels in either colon tumour or tissue preparations from full-thickness normal colon wall. An inverse correlation between serum insulin and receptor levels was, however, apparent in preparations of colonic musosa. These data indicate that although insulin receptors in colon tumours share the same biochemical characteristics as those present in the normal colon, receptors in tumour tissue are less sensitive to down-regulation by ambient insulin than receptors in mesenteric fat cells and normal colonic mucosa.


Exercise training for managing behavioral and psychological symptoms in people with dementia: A systematic review and meta-analysis.
This systematic review and meta-analysis of randomized controlled trials assessed the effects of exercise on behavioral and psychological symptoms of dementia (BPSD, including depression) in people with dementia (PWD). Secondary outcomes for the effects of exercise were mortality and antipsychotic use. Twenty studies were included in this review (n=18 in the meta-analysis). Most studies used a multicomponent exercise training (n=13) as intervention; the control group was often a usual care (n=10) or a socially-active (n=8) group. Exercise did not reduce global levels of BPSD (n=4. Weighted mean difference -3.884; 95% CI -8.969-1.201; I(2)=69.4%). Exercise significantly reduced depression levels in PWD (n=7). Standardized mean difference -0.306; 95% CI -0.571 to -0.041; I(2)=46.8%); similar patterns were obtained in sensitivity analysis performed among studies with: institutionalized people (p=0.038), multicomponent training (p=0.056), social control group (p=0.08), and low risk of attrition bias (p=0.11). Exploratory analysis showed that the principal BPSD (other than depression) positively affected by exercise was aberrant motor behavior. Exercise had no effect on mortality. Data on antipsychotics were scarce. In conclusion, exercise reduces depression levels in PWD. Future studies should examine whether exercise reduces the use (and doses) of antipsychotics and other drugs often used to manage BPSD.