CCDC74A/B are K-fiber crosslinkers required for chromosomal alignment.
Spindle microtubule organization, regulated by microtubule-associated proteins, is critical for cell division. Proper organization of kinetochore fiber (K-fiber), connecting spindle poles and kinetochores, is a prerequisite for precise chromosomal alignment and faithful genetic material transmission. However, the mechanisms of K-fiber organization and dynamic maintenance are still not fully understood. We reveal that two previously uncharacterized coiled-coil domain proteins CCDC74A and CCDC74B (CCDC74A/B) are spindle-localized proteins in mammalian cells. They bind directly to microtubules through two separate domains and bundle microtubules both in vivo and in vitro. These functions are required for K-fiber organization, bipolar spindle formation, and chromosomal alignment. Moreover, CCDC74A/B form homodimers in vivo, and their self-association activity is necessary for microtubule bundling and K-fiber formation. We characterize CCDC74A and CCDC74B as microtubule-associated proteins that localize to spindles and are important K-fiber crosslinkers required for bipolar spindle formation and chromosome alignment.


Novel dimeric structure of phage φ29-encoded protein p56: insights into uracil-DNA glycosylase inhibition.
Protein p56 encoded by the Bacillus subtilis phage φ29 inhibits the host uracil-DNA glycosylase (UDG) activity. To get insights into the structural basis for this inhibition, the NMR solution structure of p56 has been determined. The inhibitor defines a novel dimeric fold, stabilized by a combination of polar and extensive hydrophobic interactions. Each polypeptide chain contains three stretches of anti-parallel β-sheets and a helical region linked by three short loops. In addition, microcalorimetry titration experiments showed that it forms a tight 2:1 complex with UDG, strongly suggesting that the dimer represents the functional form of the inhibitor. This was further confirmed by the functional analysis of p56 mutants unable to assemble into dimers. We have also shown that the highly anionic region of the inhibitor plays a significant role in the inhibition of UDG. Thus, based on these findings and taking into account previous results that revealed similarities between the association mode of p56 and the phage PBS-1/PBS-2-encoded inhibitor Ugi with UDG, we propose that protein p56 might inhibit the enzyme by mimicking its DNA substrate.


Anoxia-inducible rat VL30 elements and their relationship to ras-containing sarcoma viruses.
VL30 elements are associated with cancer by their overexpression in rodent malignancies, their induction in a fibroblast response to anoxia which shares features with the malignant phenotype, and their presence recombined into Harvey murine sarcoma virus (HaSV) and Kirsten murine sarcoma virus. These sarcoma viruses contain ras oncogenes flanked on both sides by retrotransposon VL30 element sequences, in turn flanked by mouse leukemia virus sequences. Three very basic questions have existed about the VL30 element sequences found in sarcoma viruses: (i) how did they become recombined, (ii) what are their exact boundaries, and (iii) why are they there? To help decipher the nature of VL30 elements in sarcoma viruses, we examined VL30 clones isolated from an anoxic fibroblast cDNA library and independently by polymerase chain reaction cloning from rat cell DNA. Sequence comparisons with HaSV revealed that HaSV was formed by the substitution of 0.7 kb of VL30 sequences by 0.9 kb of c-Ha-ras sequences, with this event possibly facilitated by the presence of an identical Alu-like repeat found upstream of the 5' recombination point in both the VL30 element and c-Ha-ras. Recombination occurred 42 bases beyond the Alu-like sequences in VL30 and 1596 bases beyond them in c-Ha-ras, at position 926 of HaSV. The 3' ras-VL30 recombination event in HaSV occurred within a seven-base region of shared sequence identity, between HaSV bases 1825 and 1825 and 1831. Recombination between Moloney leukemia virus (MoLV) and VL30 appears to have occurred at a point corresponding to base 218 or 219 of MoLV and was near a TAR-like VL30 sequence; such recombination at the 3' end was between positions 7445 and 7456 of MoLV (HaSV positions 4694 to 4703). Kirsten murine sarcoma virus was found to be closely analogous to HaSV, and limited similar features were also seen with Rasheed sarcoma virus.


Vision Permutator: A Permutable MLP-Like Architecture for Visual Recognition.
In this paper, we present Vision Permutator, a conceptually simple and data efficient MLP-like architecture for visual recognition. By realizing the importance of the positional information carried by 2D feature representations, unlike recent MLP-like models that encode the spatial information along the flattened spatial dimensions, Vision Permutator separately encodes the feature representations along the height and width dimensions with linear projections. This allows Vision Permutator to capture long-range dependencies and meanwhile avoid the attention building process in transformers. The outputs are then aggregated in a mutually complementing manner to form expressive representations. We show that our Vision Permutators are formidable competitors to convolutional neural networks (CNNs) and vision transformers. Without the dependence on spatial convolutions or attention mechanisms, Vision Permutator achieves 81.5% top-1 accuracy on ImageNet without extra large-scale training data (e.g., ImageNet-22k) using only 25M learnable parameters, which is much better than most CNNs and vision transformers under the same model size constraint. When scaling up to 88M, it attains 83.2% top-1 accuracy, greatly improving the performance of recent state-of-the-art MLP-like networks for visual recognition. We hope this work could encourage research on rethinking the way of encoding spatial information and facilitate the development of MLP-like models. PyTorch/MindSpore/Jittor code is available at https://github.com/Andrew-Qibin/VisionPermutator.


[Recurrences of epithelial tumors of the head and neck: review of the literature and a critical analysis of the problem].
Recurrence is a tumor renewal in a previously treated field or surgical wound after a disease-free period. The present work investigates loco-regional recurrences. In the first part of the work the most frequent recurrence sites, types and their characteristics (i.e. infiltrating, exophytic, ulcerating) are studied along with the problems in clinical and pathological diagnosis, new diagnostic imaging (CT and MR) and the UICC classification system. The second part of the work is dedicated to examining classical treatments (surgery, radiotherapy, chemotherapy and radiochemotherapy associations) as well new therapies (i.e. cryosurgery, hyperthermia, immunotherapy, photodynamic therapy). A review of the literature is made for indications, results and complications. An extensive study of the cases of the Head and Neck Group of the University of Turin during the 1983-1990 period is also reported. This experience is based on 312 cases: 68 (oropharynx and larynx) treated by surgery, 51 (neck nodes and stomal recurrences) treated by radiotherapy and hyperthermia, 35 (neck nodes) by hyperthermia alone, 168 (all sites) by chemotherapy and 20 by immunotherapy. In the third part of this work supportive therapies and practical problems are reported. In conclusion a therapeutic approach is proposed in relation to the site of the recurrence and previous treatments.


Cognitive dysfunction in systemic lupus erythematosus: prevalence and correlates.
Little is known about the mechanisms and relevance of cognitive dysfunction in systemic lupus erythematosus (SLE) patients who never displayed major neuropsychiatric manifestations (nSLE). Thirty-one nSLE female patients and 31 cognitively healthy control women were recruited. Sociodemographic, clinical, neuropsychological and SLE-related markers were collected including cerebral perfusion by single-photon emission computed tomography. Prevalences of cognitive complaints were 22.6% in nSLE versus 6.5% in the control group (p = 0.147); respective prevalences of cognitive dysfunction were 32.3 versus 6.5% (p = 0.01). Within the nSLE group, all cognitive domains appeared similarly affected, and correlations were found between cognitive dysfunction and less skilled occupation (r = -0.41, p = 0.02) and between cognitive complaints and depressive symptoms (r = 0.35, p = 0.05). Cognitive dysfunction is rather frequent in nSLE and seems to negatively impinge on social functioning.


Harnessing affinity-based protein profiling to reveal a novel target of nintedanib.
Nintedanib (BIBF1120), a triple angiokinase inhibitor, was first approved for idiopathic pulmonary fibrosis (IPF) therapy and is also efficacious for lung carcinoma, and interstitial lung diseases, far beyond its inhibition of VEGFR/PDGFR/FGFR. We identified tripeptidyl-peptidase 1 (TPP1) as one of the direct targets of nintedanib employing the affinity-based protein profiling (AfBPP) technique. This may be a new mechanism for nintedanib's role different from tyrosine kinase inhibition.


[Termination of slow ventricular tachycardia which is below ICD detection rate - a case report].
Slow ventricular tachycardia (VT), which is below the detection rate of implantable cardioverter-defibrillator may cause haemodynamical instability, when pharmacological agents or antitachycardia pacing are unsuccessful, electrical cardioversion is necessary. We present another method of termination of slow VT by ICD, in which transcutaneous pacing mimics faster VT and triggers ICD discharge.


Gap junction assembly: multiple connexin fluorophores identify complex trafficking pathways.
The assembly of gap junction channels was studied using mammalian cells expressing connexin (Cx) 26, 32 and 43 in which the carboxyl terminus was fused to green, yellow or cyan fluorescent proteins (GFP, YFP, CFP). Intracellular targeting of Cx32-CFP and 43-GFP to gap junctions was disrupted by brefeldin A treatment and resulted in a severe loss of gap junctional intercellular communication reflected by low intercellular dye transfer. Cells expressing Cx43-GFP exposed to nocodazole showed normal targeting to gap junctions and dye transfer. Cx32 and 43 thus appear to be transported and assembled into gap junctions via the classical secretory pathway. In contrast, we found that assembly of Cx26-GFP into functional gap junctions was relatively unaffected by treatment of cells with brefeldin A, but was extremely sensitive to nocodazole treatment. Coexpression of Cx26-YFP and Cx32-CFP indicated a different intracellular distribution that was accentuated in the presence of brefeldin A, with the gap junctions in these cells constructed predominantly of Cx26-YFP. A site specific mutation in the first transmembrane domain that distinguished Cx32 from Cx26 (Cx32128L) resulted in the adoption of the trafficking properties of Cx26 as well as its unusual post-translational membrane integration characteristics. The results indicate that multiple intracellular connexin trafficking routes exist and provide a further mechanism for regulating the connexin composition of gap junctions and thus specificity in intercellular signalling.


Effect of ethanol on plasma and hepatic insulin-like growth factor regulation in pregnant rats.
Alcohol consumption during pregnancy has been shown to have profound developmental and behavioral effects on the fetus; however, the specific cause of these abnormalities remains unknown. These studies examined the consequences of chronic ethanol exposure during pregnancy on the regulation of maternal plasma and hepatic insulin-like growth factors (IGFs), and their associated plasma binding proteins (IGF-BPs). Ad libitum, pair, and ethanol-fed rats were fed a commercial liquid diet containing either ethanol or isocaloric maltose-dextrin from day 2 of pregnancy through parturition and killed 6 hr postpartum. Maternal plasma IGF-1 concentrations were reduced 51% in ethanol, compared with pair-fed mothers, with a corresponding 20% reduction in hepatic IGF-1 mRNA levels. In contrast, plasma IGF-2 concentrations were increased approximately 100% in ethanol-fed mothers. Whereas the smaller forms of the IGF-binding protein subunits (24 kDa and 32-29 kDa) were not affected by ethanol treatment, a significant reduction was observed in the binding subunit of IGF-BP3 (45-40 kDa) in ethanol-exposed mothers. These results suggest that alterations in plasma and hepatic IGF regulation may contribute to changes in maternal and placental metabolism and hormone regulation during pregnancy, which may in turn contribute to the intrauterine and postnatal growth retardation observed in prenatally ethanol-exposed offspring.


Retinal thinning in Gaucher disease patients and carriers: results of a pilot study.
Both Gaucher disease patients and heterozygous glucocerebrosidase mutation carriers are at increased risk of Parkinson's disease. Retinal thinning has been reported in early Parkinson's disease. Here we used optical coherence tomography to demonstrate thinning of the retinal ganglion cell layer in Gaucher disease patients and carriers who manifest clinical markers of potential early neurodegeneration. Optical coherence tomography may help identify Gaucher disease patients and carriers at increased risk of developing Parkinson's disease.


Revision of the Cyclisation Mechanism for the Diterpene Spiroviolene and Investigations of Its Mass Spectrometric Fragmentation.
The diterpene spiroviolene, its diterpene synthase from Streptomyces violens and the experimentally determined terpene cyclisation mechanism were reported in 2017. Recently, the structure of spiroviolene was revised based on a total synthesis, with consequences for the cyclisation mechanism. Herein, a reinvestigation of the terpene cyclisation to spiroviolene and the mass spectrometric fragmentation mechanism investigated by 13 C-labelling experiments are presented.


Open-loop correction of horizontal turbulence: system design and result.
Adaptive optics systems often work in a closed-loop configuration due to the hysteretic and nonlinearity properties of conventional deformable mirrors. Because of the high-precision wavefront generation and nonhysteretic properties of liquid-crystal devices, the open-loop control becomes possible. Open-loop control is a requirement for advanced adaptive optics concepts. We designed an open-loop adaptive optics system with a liquid-crystal-on-silicon wavefront corrector. This system is simple, fast, and can save much more light compared to conventional liquid-crystal-based closed-loop systems. The detailed principle, construction, and operation are discussed. The 500 m horizontal turbulence correction experiment was done using a 250 mm telescope in the laboratory. The whole system can reach a 60 Hz correction frequency. Evaluation of the correction precision was done at closed-loop configuration, which is 0.2 lambda (lambda=0.633 microm) in peak to valley. The dynamic image under open-loop correction got the same resolution compared to closed-loop correction. The whole system reached 0.68 arc sec resolution capability at open-loop correction, which is slightly larger than the system's diffraction-limited resolution of 0.65 arc sec.


In vivo tracking of mesenchymal stem cells labeled with a novel chitosan-coated superparamagnetic iron oxide nanoparticles using 3.0T MRI.
This study aimed to characterize and MRI track the mesenchymal stem cells labeled with chitosan-coated superparamagnetic iron oxide (Chitosan-SPIO). Chitosan-SPIO was synthesized from a mixture of FeCl(2) and FeCl(3). The human bone marrow derived mesenchymal stem cells (hBM-MSC) were labeled with 50 microg Fe/mL chitosan-SPIO and Resovist. The labeling efficiency was assessed by iron content, Prussian blue staining, electron microscopy and in vitro MR imaging. The labeled cells were also analyzed for cytotoxicity, phenotype and differentiation potential. Electron microscopic observations and Prussian blue staining revealed 100% of cells were labeled with iron particles. MR imaging was able to detect the labeled MSC successfully. Chitosan-SPIO did not show any cytotoxicity up to 200 microg Fe/mL concentration. The labeled stem cells did not exhibit any significant alterations in the surface markers expression or adipo/osteo/chondrogenic differentiation potential when compared to unlabeled control cells. After contralateral injection into rabbit ischemic brain, the iron labeled stem cells were tracked by periodical in vivo MR images. The migration of cells was also confirmed by histological studies. The novel chitosan-SPIO enables to label and track MSC for in vivo MRI without cellular alteration.


[Biochemical symptoms of hypothyreosis in the population of Warsaw region].
Doctors in Warsaw region claimed that the results of fT4 and TSH examinations originating from different laboratories are incomparable. Therefore the Gaussian Reference Ranges (GRR) of archival sets of data from 6 laboratories (together 18793 fT4 and 44851 TSH results) were calculated separately with JEG method. The upper and lover ranges were compared with data from 11 bibliographical sources. It was found that in the investigated population the both averaged ranges (high and low) of GRR of fT4 are statistical significant lover then the reference data. In the same time the averaged upper range of GRR of TSH was higher than the averaged data from the literature. Based on statistic analysis of these results it could be estimated that about 20% of the investigated population show evident and about 50% show moderate signs of hypothyreosis.


[Epidemiological characteristics of newly reported HIV infections in Chinese and Burmese residents, during 2012-2016 in Dehong Dai and Jingpo Autonomous Prefecture, Yunnan province].
Objective: To understand the epidemiological characteristics of newly reported HIV infections in Chinese and Burmese residents during 2012-2016 in Dehong Dai and Jingpo Autonomous Prefecture of Yunnan province (Dehong) and to provide evidence for the development of related programs on prevention and control. Methods: All the HIV infections who were newly reported during 2012-2016 in Dehong, were recruited as the study subjects, with epidemiological characteristics of the cases analyzed by using the software SPSS 22.0. Results: A total of 5 692 HIV infections were newly reported between 2012 and 2016 (including 5 592 in this study), in which the Chinese patients accounted for 43.3% (2 419) and the rest 56.7% (3 173) were Burmese. Differences in age, gender and other social characteristics of these newly reported HIV infections were statistically significant between the Chinese and the Burmese (all p-values <0.05). Most cases were males and between the age of 20-49 years old. Other characteristics of the patients would include: having had primary school education, married, being farmers, and with CD(4)(+)T cells counts ≥350 cells/μl. HIV infection was mainly transmitted through sexual contact among the Chinese patients but through injecting drug use among the Burmese patients. Conclusions: Epidemiological characteristics of the newly reported HIV infections were different between the Chinese and the Burmese, between 2012 and 2016 in Dehong. Targeted prevention and control programs should be taken.


In vivo antitumor activity of Sindbis viral vectors.
Sindbis virus, a blood-borne virus transmitted by mosquitoes, has been used as a vector to efficiently express exogenous genes in vitro and in vivo and to induce apoptosis. Because Sindbis virus infects mammalian cells by interacting with the high-affinity laminin receptors, which are expressed at higher levels in several human cancers than in normal cells, we determined whether a Sindbis viral vector could be used to target cancers in vivo. C.B-17-SCID mice with established xenografts were given daily intraperitoneal injections of the Sindbis viral vector SinRep/LacZ containing the bacterial beta-galactosidase gene. Control mice were untreated or received injections with phosphate-buffered saline. Tumor size was measured daily. Expression of beta-galactosidase and Factor VIII (a marker for endothelial cells) was determined by immunohistochemical staining of tumor sections. Apoptosis was analyzed by TUNEL (terminal deoxynucleotidyl transferase [TdT]-mediated dUTP nick end labeling) staining. C.B-17-SCID beige mice, which lack natural killer (NK) cells, were used to assess the importance of NK cells in antitumor efficacy of Sindbis viral vectors. Tumors from mice treated with SinRep/LacZ were statistically significantly smaller than tumors from control mice. This effect was observed for tumor xenografts derived from BHK (kidney, hamster), LS174T (colon, human), HT29 (colon, human), and CFPAC (pancreas, human) cells. Expression of beta-galactosidase co-localized with that of Factor VIII in tumor sections. Tumors from SinRep/LacZ-treated mice contained more apoptotic cells than tumors from control mice. Complete tumor regression was observed in three of five C.B-17-SCID mice but in none of five C.B-17-SCID beige mice treated with SinRep/LacZ. Sindbis viral vectors efficiently targeted tumors in vivo, were apparently delivered through the circulation, and were more effective in the presence of NK cells.


Elective Hand Surgery in Patients With History of Axillary Node Dissection: Risks and Patient Education.
To determine if patients with a prior history of axillary lymph node dissection (ALND) secondary to breast cancer surgery and other procedures are at an increased risk of postoperative complications including lymphedema and infection following elective upper extremity surgery. Furthermore, the study aimed to evaluate the extent of patient education regarding lymphedema as a possible complication of upper extremity surgery. A review of 312 patients presenting to the clinic with upper extremity pathologies was performed of which 15 patients had a history of surgeries secondary to breast cancer and 297 had no prior history of breast cancer. Nine out of 15 patients with prior breast procedures and 66 out of 297 patients with no such history underwent elective hand surgeries, with 22 out of the 75 patients having a history of ALND. Incidences of postoperative complications including lymphedema and infection were recorded. Afterward, a survey inquiring about patient education was conducted to assess whether the patients were educated regarding lymphedema and if so, when and from whom they received the counseling. No patients with a prior history of ALND secondary to breast cancer or other surgeries developed a postoperative infection or onset of lymphedema, and no patients with preoperative lymphedema had any worsening of lymphedema or infection postoperatively. The survey conducted afterward revealed that 61% of the patients with a prior history of breast cancer-related procedures including lymph node dissection were never counseled regarding lymphedema as a possible complication of hand surgery. Furthermore, 75% of the survey participants wished they were given more information about possible causes and complications of, and ways to prevent or minimize the possibility of lymphedema developing postoperatively. Prior history of ALND did not make patients more susceptible to postoperative complications, thus a history of isolated ALND or breast cancer surgery including ALND should not preclude elective hand surgical procedures from being performed ipsilaterally. Additionally, improvements in the degree of patient counseling regarding postoperative complications following hand surgery are needed as increased patient education is shown to be associated with a lower rate of complications and faster recovery times.


Profile of specific and associated autoantibodies in patients with idiopathic inflammatory myopathies in a Colombian population.
Idiopathic inflammatory myopathies (IIMs) are chronic, autoimmune diseases with several forms of presentation. Diagnosis is mostly clinical in our region. Our aim was to evaluate the autoantibody profile of patients with IIMs. This study is a cross-sectional study with a prospective recollection of data, conducted between 2019-2021, in a single center in Cali, Colombia. Patients with a clinical diagnosis or suspicion of IIM were included. The presence of myositis-specific/associated antibodies was evaluated by immunoblotting in serum samples. Phenotypic characterization was performed. A total of 36 patients were included. The mean age was 50.6 (16.7) years, and 20 (55.6%) were female. Eighteen (50%) patients were seropositive, of which 11 (30.5%) presented one positive antibody, with anti-TIF1ɣbeing the most frequent (n = 4, 11.1%), followed by anti-Ro52 (n = 2, 5.6%). Seven patients (19.4%) showed >1 positive antibody. Dermatomyositis was the most frequent type of IIM in seropositive patients (n = 8, 44.4%), followed by anti-synthetase syndrome (n = 4, 22.2%). Weakness was symmetric and presented in the upper and lower extremities in 11 (61.1%) patients each. Both respiratory insufficiency and weight loss were seen in 7 (38.9%) patients, Gottron papules in six (33.3%) patients, and heliotrope rash, esophageal dysmotility, and myalgia in 5 (27.8%) patients. Pulmonary interstitial disease was seen in 4 (22.2%, with antibodies for anti-Ro52, anti-MDA5 + anti-Jo1 + anti-TIF1ɣ, anti-MDA5 + anti-SAE1 + anti-NXP2, and anti-cN1A + anti-Ro52) patients, and malignancy was seen in 2 (11.1%) patients (1 with anti-Mi2β and 1 with anti-TIF1ɣ + anti-Mi2α). In all, 7 (19.4%) patients required intensive care (2 seropositive, 1 with anti-PL7, 1 with anti-MDA5 + anti-Jo1 + anti-TIF1ɣ), and 1 (2.8%) (seronegative) patient died. This study is the first study in the Southwest of Colombia that evaluates myositis-specific/associated antibodies in IIM. Half of the patients were seropositive. Anti-TIF1ɣwas the most frequent MSA and anti-Ro52 was the most frequent MAA. Several patients presented antibody combinations. Further studies are needed to fully associate phenotypes with antibodies.


Reborn a virgin: adolescents' retracting of virginity pledges and sexual histories.
We examined retractions of virginity pledges and of sexual histories among adolescents taking part in waves 1 and 2 of the National Longitudinal Study of Adolescent Health. Logistic regression analyses were used to compare respondents' reports of virginity pledges and sexual histories at waves 1 and 2.Results. Among wave 1 virginity pledgers, 53% denied having made a pledge at wave 2; after control for confounders, pledgers who subsequently initiated sexual activity were 3 times as likely to deny having made a pledge as those who did not initiate sexual activity (odds ratio [OR] = 3.21; 95% confidence interval [CI] = 2.04, 5.04). Among wave 1 nonvirgins who subsequently took virginity pledges, 28% retracted their sexual histories at wave 2; respondents who took virginity pledges were almost 4 times as likely as those who did not to retract reports of sexual experience (OR=3.88; 95% CI=1.87, 8.07). Adolescents who initiate sexual activity are likely to recant virginity pledges, whereas those who take pledges are likely to recant their sexual histories. Thus, evaluations of sexual abstinence programs are vulnerable to unreliable data. In addition, virginity pledgers may incorrectly assess the sexually transmitted disease risks associated with their prepledge sexual behavior.


CD40, an extracellular receptor for binding and uptake of Hsp70-peptide complexes.
Tumor and viral antigens elicit a potent immune response by heat shock protein-dependent uptake of antigenic peptide with subsequent presentation by MHC I. Receptors on antigen-presenting cells that specifically bind and internalize a heat shock protein-peptide complex have not yet been identified. Here, we show that cells expressing CD40, a cell surface protein crucial for B cell function and autoimmunity, specifically bind and internalize human Hsp70 with bound peptide. Binding of Hsp70-peptide complex to the exoplasmic domain of CD40 is mediated by the NH(2)-terminal nucleotide-binding domain of Hsp70 in its ADP state. The Hsp70 cochaperone Hip, but not the bacterial Hsp70 homologue DnaK, competes formation of the Hsp70-CD40 complex. Binding of Hsp70-ADP to CD40 is strongly increased in the presence of Hsp70 peptide substrate, and induces signaling via p38. We suggest that CD40 is a cochaperone-like receptor mediating the uptake of exogenous Hsp70-peptide complexes by macrophages and dendritic cells.


Perspectives on Telehealth for older adults during the COVID-19 pandemic using the quadruple aim: interviews with 48 physicians.
Telehealth delivery expanded quickly during the COVID-19 pandemic after the reduction of payment and regulatory barriers, but older adults are the least likely to benefit from this expansion. Little is known about physician experiences initiating telehealth and factors that fostered or discouraged adoption during the COVID-19 pandemic with older adult patients. Therefore, our objective was to understand experiences of frontline physicians caring for older adults via telehealth during the COVID-19 pandemic. We conducted semi-structured interviews from September 2020 to November 2020 with 48 physicians. We recruited a diverse sample of geriatricians (n = 18), primary care (n = 15), and emergency (n = 15) physicians from all United Stated (US) regions, rural-urban settings, and academic-community practices who cared for older adult patients during the pandemic using purposive sampling methods. We completed framework analysis of the transcribed interviews to identify emerging themes and used the Quadruple Aim to organize themes. Frontline physicians described telehealth as a more flexible, value-based, and patient-centered mode of health care delivery. Benefits of using telehealth to treat older adults included reducing deferred care and increasing timely care, improving efficiency for physicians, enhancing communication with caregivers and patients, reducing patient travel burdens, and facilitating health outreach and education. Challenges included unequal access for rural, older, or cognitively impaired patients. Physicians noted that payment parity with in-person visits, between video and telephone visits, and relaxation of restrictive regulations would enhance their ability to continue to offer telehealth. Frontline physicians who treated older adults during the COVID-19 pandemic were largely in favor of continuing telehealth use beyond the pandemic; however, they noted that sustainability would depend on enacting policies that address access inequities and reimbursement concerns. Our data provide policy insights that if placed into action could facilitate the long-term success of telehealth and encourage a more flexible healthcare delivery system in the US.


Obesity-related knowledge and beliefs in obese adults attending a specialist weight-management service: implications for weight loss over 1 year.
Cognitive approaches to obesity management assume that weight loss is more likely to occur if individuals perceive many benefits and few costs. Research to-date has been limited by the lack of prospective studies. A longitudinal study design. At baseline, obese patients attending weight-management clinics (n=104) completed a questionnaire that assessed knowledge and beliefs regarding obesity's health and social/aesthetic consequences (Obesity Risk Knowledge (ORK-10) scale and the Obesity Beliefs scale), self-reported weight/height, goal weight, health-related quality of life, and sociodemographic characteristics. Medical records were also reviewed. At the 12-month follow-up, a second questionnaire assessed self-reported weight/height. At baseline, average ORK-10 scale scores were 4/10. At follow-up, 32 out of the 66 participants retained on the study did not gain weight (48.5%). For these participants, weight loss was associated with endorsement of the health (r(s)=0.40) and the social/aesthetic (r(s)=0.31) costs of obesity (p<0.05). Despite their high-risk status, participants demonstrated low levels of knowledge regarding obesity's health risks. Weight loss was associated with greater awareness of the health and social/aesthetic costs of obesity. This study suggests that health education is required to facilitate informed choices and supports the use of cognitive approaches which promote both the health and social/aesthetic consequences of obesity.


Can urethral re-bulking improve the outcomes of a prior urethral bulking?
To analyze the outcomes of urethral re-bulking in the treatment of female stress urinary incontinence. We performed a multicenter observational retrospective study, which included all consecutive patients treated with urethral re-bulking for the treatment of persistent stress or mixed urinary incontinence after a previous urethral bulking. Objective outcomes were evaluated with the 24 h pad-test, while PGI-I questionnaires were administered to evaluate subjective outcomes. Clinical outcomes were assessed before re-bulking procedure and at last follow-up. Mann-Whitney's U test was used for subgroup analysis. Shapiro-Wilk's tests were used as normality tests. In total, 62 patients who underwent urethral re-bulking between 2013 and 2020 in a multicenter setting were included. Most patients did not reach complete continence after the first procedure (n = 56) while the remainder reported recurrence of urinary incontinence after initial benefit. Median age at surgery was 66 (IQR: 55-73). Median overall follow-up was 30 months (IQR: 24-41). Median time occurred between the first procedure and reintervention was 12 months (IQR: 7-27). Bulking agents for the re-bulking procedures were bulkamid(n = 56), macroplastique(n = 4), and Prolastic(n = 2). A statistically significant reduction of median 24 h pad test from 100 g(IQR: 40-200) to 35 g(IQR: 0-120) was observed (p = 0.003). Dry rate after rebulking was 36.6%, while 85.4% patients declared themselves 'very much improved' or 'much improved' (PGI-I 1-2). Very few low-grade complications were observed (n = 4). A single case of major complication occurred. Urethral re-bulking can be an effective technique for the treatment of stress urinary incontinence refractory to a previous urethral bulking and can determine a cumulative benefit after the first procedure.


Primary ovarian mucinous carcinoid arising in a mature cystic teratoma-A rare entity.
Mature cystic teratomas are benign unilateral tumors often diagnosed in young females. Carcinoid tumors are slow-growing tumors originating from neuroendocrine cells. A thorough histopathological study of the tumor is mandatory and the surgical treatment is adapted according to the characteristics of the patient. The present case was considered as a primary mucinous carcinoid tumor of the ovary because it was confined to the ovary, had an intact capsule, no vascular invasion, or other suspicious lesions were noted in the abdominal cavity. This case is notable due to the rarity of its occurrence and the age of presentation.


Inhibition of JNK signaling in the Asian malaria vector Anopheles stephensi extends mosquito longevity and improves resistance to Plasmodium falciparum infection.
Malaria is a global health concern caused by infection with Plasmodium parasites. With rising insecticide and drug resistance, there is a critical need to develop novel control strategies, including strategies to block parasite sporogony in key mosquito vector species. MAPK signaling pathways regulated by extracellular signal-regulated kinases (ERKs) and the stress-activated protein kinases (SAPKs) c-Jun N-terminal kinases (JNKs) and p38 MAPKs are highly conserved across eukaryotes, including mosquito vectors of the human malaria parasite Plasmodium falciparum. Some of these pathways in mosquitoes have been investigated in detail, but the mechanisms of integration of parasite development and mosquito fitness by JNK signaling have not been elucidated. To this end, we engineered midgut-specific overexpression of MAPK phosphatase 4 (MKP4), which targets the SAPKs, and used two potent and specific JNK small molecule inhibitors (SMIs) to assess the effects of JNK signaling manipulations on Anopheles stephensi fecundity, lifespan, intermediary metabolism, and P. falciparum development. MKP4 overexpression and SMI treatment reduced the proportion of P. falciparum-infected mosquitoes and decreased oocyst loads relative to controls. SMI-treated mosquitoes exhibited no difference in lifespan compared to controls, whereas genetically manipulated mosquitoes exhibited extended longevity. Metabolomics analyses of SMI-treated mosquitoes revealed insights into putative resistance mechanisms and the physiology behind lifespan extension, suggesting for the first time that P. falciparum-induced JNK signaling reduces mosquito longevity and increases susceptibility to infection, in contrast to previously published reports, likely via a critical interplay between the invertebrate host and parasite for nutrients that play essential roles during sporogonic development.


A novel pH-dependent gradient-release delivery system for nitrendipine II. Investigations of the factors affecting the release behaviors of the system.
Nitrendipine, a dihydropyridine calcium antagonist, was used as a poorly water-soluble model drug. To improve its dissolution rate and extend the therapeutic period in vivo as well, a novel pH-dependent gradient-release drug delivery system for nitrendipine having a solid dispersed matrix structure was developed. Four factors, i.e. the amount of excipients, the pH of the dissolution medium, the rotating speed of the paddle of the dissolution apparatus and the particle size of the microspheres, all of which affect the drug-release behavior of the pH-dependent microspheres of the system were investigated in detail. The release profiles of the pH-dependent drug delivery system under simulated gastrointestinal tract pH conditions were also investigated. The results showed that the release rate of drug from the microspheres increased on increasing the amount of respective pH-dependent polymers formulated. Due to the fact that the active drug was incorporated in pH-dependent polymers and was present in a solid dispersion state in the microspheres, the release rate of the drug from the microspheres depended on the dissolution rate of the polymers, which was mainly influenced by the pH of dissolution medium, whereas the rotating speed of the paddle and the particle size of the microspheres had only a relatively minor effect. The release behavior of the system under simulated gastrointestinal tract conditions exhibited obvious gradient-release characteristics, showing that the release rate of the active drug could be controlled efficiently before the microspheres reached the appropriate region of the gut for absorption. These findings suggest that the pH-dependent drug delivery system could be fabricated by using present microspheres.


Hemoglobin variability in patients with chronic kidney disease in the Netherlands.
Hemoglobin cycling has been reported in hemodialysis patients treated with erythropoiesis-stimulating agents (ESA) and is associated with increased mortality. Information on hemoglobin cycling in Europe is limited. We investigated hemoglobin variability in the Netherlands. Hemodialysis and peritoneal dialysis patients were studied and pre-dialysis patients were enrolled. This observational retrospective study was executed in a Dutch dialysis center. We studied 157 patients from 2005 to 2007: 56 hemodialysis, 12 peritoneal dialysis and 29 pre-dialysis patients, all treated with ESA; and 60 pre-dialysis patients without ESA. Patients were divided on the basis of their pattern of hemoglobin fluctuation around a range of 11-12 g/dL. In dialysis patients, the amount of time that hemoglobin remained within that range was calculated. For all patients, the magnitude of hemoglobin fluctuations was assessed (i.e. the difference between hemoglobin maximum and minimum) and data on ESA dose changes and hospitalizations were collected. None of the ESA treated patients had hemoglobin levels stable within the target range over a one-year period. Pre-dialysis patients without ESA also showed variable hemoglobin levels. A stepwise decrease in the magnitudes of hemoglobin fluctuation was observed in the hemodialysis patients, peritoneal dialysis patients, pre-dialysis patients using ESA, and the pre-dialysis patients without ESA, respectively. In the Netherlands, hemoglobin variability is common in hemodialysis and peritoneal dialysis patients, but also in pre-dialysis patients. The results of this study warrant further research into the relationship between hemoglobin variability and clinical outcomes.


New Insights into Intrinsic Point Defects in V2VI3 Thermoelectric Materials.
Defects and defect engineering are at the core of many regimes of material research, including the field of thermoelectric study. The 60-year history of V2VI3 thermoelectric materials is a prime example of how a class of semiconductor material, considered mature several times, can be rejuvenated by better understanding and manipulation of defects. This review aims to provide a systematic account of the underexplored intrinsic point defects in V2VI3 compounds, with regard to (i) their formation and control, and (ii) their interplay with other types of defects towards higher thermoelectric performance. We herein present a convincing case that intrinsic point defects can be actively controlled by extrinsic doping and also via compositional, mechanical, and thermal control at various stages of material synthesis. An up-to-date understanding of intrinsic point defects in V2VI3 compounds is summarized in a (χ, r)-model and applied to elucidating the donor-like effect. These new insights not only enable more innovative defect engineering in other thermoelectric materials but also, in a broad context, contribute to rational defect design in advanced functional materials at large.


[Femtosecond laser-assisted corneoscleral lamellar keratoplasty for peripheral corneal disease].
Objective: To evaluate the effect of femtosecond laser-assisted corneoscleral lamellar keratoplasty (FL-CSLK) on peripheral corneal disease (PCD). Methods: Retrospective cohort study. Six patients (6 eyes) with PCD who underwent FL-CSLK in Qingdao Eye Hospital from March 2014 to March 2017 were grouped as the FL-CSLK group, including 4 males and 2 females, aged (46.7±17.9) years. In addition, 8 patients (8 eyes) with PCD who underwent traditional corneoscleral lamellar keratoplasty in the same period were included in the control group. The items for analyses were as follows: visual function recovery, including visual acuity, equivalent spherical power, and astigmatism; the state of the cornea, including the healing time of the corneal epithelium, the transparency of the graft, the thickness of the corneal graft and implant bed, and the loss rate of corneal endothelial cells; intraoperative and postoperative complications, including high intraocular pressure, interlayer effusion, delayed corneal epithelial healing, immune rejection, and primary recurrence. Paired t-test was used to compare the best corrected visual acuity (BCVA), equivalent spherical power, and astigmatism before and after operation. The BCVA and corneal graft epithelial healing time between the two groups were compared by independent sample t-test. Results: The 6 patients in the FL-CSLK group included 2 cases of Mooren ulcer, 3 cases of Terrien marginal degeneration, and 1 case of pellucid marginal degeneration. The control group consisted of 4 eyes with Mooren ulcer and 4 eyes with Terrien marginal degeneration. The BCVA (logarithm of the minimum angle of resolution) in the FL-CSLK group was 0.35±0.09 at 6 months after operation, which was significantly higher than that before operation (1.17±0.15; t=9.01, P<0.001) and at 6 months after operation in the control group (0.78±0.29; t=-3.96, P=0.003). The equivalent spherical power was (4.8±2.7) D, lower than that before operation (t=-3.71, P=0.014), and the astigmatism power was (10.1±4.1) D, lower than that before operation (t=6.04, P=0.002) in the FL-CSLK group. The healing time of the graft epithelium in the FL-CSLK group and control group was (8.5±3.3) days and (12.8±6.1) days, respectively, with no significant difference (t=-1.54, P=0.149). The central thickness of the graft in the FL-CSLK group was (525±47) μm at 6 months after operation, the central thickness of the implant bed was (189±119) μm, and the loss rate of the corneal endothelium was 7.5%±2.1%. In the control group, 1 case had intraoperative perforation, 2 cases had intracorneal hemorrhage, and 1 case had intracorneal epithelial implantation cysts and graft ulcer. There were no intraoperative and postoperative complications in the FL-CSLK group. Conclusions: FL-CSLK can yield good clinical results in the treatment of PCD. The smooth optical interface made by femtosecond lasers can help the patient achieve a good visual prognosis. The procedure reduces the risk of corneal perforation and thus improves the surgery safety.


Exploring gender distribution in patients with acute stroke: A multi-national approach.
Gender distribution of acute stroke patients varies considerably among stroke registries throughout the world, but factors responsible for this phenomenon remained vastly unknown. Using data from prospective hospital-based stroke registries in China (n = 752 acute stroke patients), Germany (n = 96054), India (n = 1500), and Iran (n = 1392), this descriptive study explored gender distribution of stroke patients and its determinants. In addition, the proportions of males and females to be expected in fictive study populations were calculated, and differences in gender distribution between stroke databases throughout the world were described. In the German dataset, a maximum male preponderance was found for patients aged between 55 and 64 years (proportion of male patients 0.67 [95% CI: 0.66-0.67]), whereas patients older than 84 years revealed a strong overbalance of females (0.27 [0.26-0.28]). In Germany, age-specific gender distribution of stroke patients is well explained by the numbers of females and males in the general population and by gender-specific stroke incidence rates. Both in China and India, a strong preponderance of male stroke patients was found for the majority of age categories with a maximum proportion of male patients of 0.82 in the 35-44 years age group. In contrast, the Iranian stroke register revealed an overbalance of females (0.13 [0.11-0.14]) in nearly all age categories. A total of 1392 Iranian ischemic stroke patients (738 female, 654 male) were investigated. Gender distribution of acute stroke patients is highly variable. Gender distribution varied considerably between countries. Apart from demographic factors reflecting gender ratio in the general population and gender-specific stroke incidence rates, sociocultural peculiarities may also play an important role in this context.


SMYD3 as an oncogenic driver in prostate cancer by stimulation of androgen receptor transcription.
Androgen receptor (AR) is critical for prostate tumorigenesis and is frequently overexpressed during prostate cancer (PC) progression. However, few studies have addressed the epigenetic regulation of AR expression. We analyzed SMYD3 expression in human PC with Western blot and immunohistochemistry. SMYD3 expression was knocked down using short hairpin RNA (shRNA) or small interfering RNA (siRNA). Cell proliferation, colony formation, and apoptosis analyses and xenograft transplantation were performed to evaluate the impact of SMYD3 depletion on PC cells. AR expression and promoter activity were determined using real-time quantitative polymerase chain reaction, western blot, and luciferase reporter assay. AR promoter association with Sp1, SMYD3, and histone modifications was assessed by chromatin immunoprecipitation. Differences in AR mRNA abundance and promoter activity were analyzed using Wilcoxon signed-rank tests, SMYD3 expression was analyzed using with Mann-Whitney U tests for unpaired samples, and tumor weight was analyzed with Student t test. All statistical tests were two-sided. The upregulation of SMYD3 protein expression was observed in seven of eight prostate tumor specimens, compared with matched normal tissues. Immunohistochemical analysis showed a strong SMYD3 staining in the nuclei of PC tissues in eight of 25 (32%) cases and in the cytoplasm in 23 out of 25 (92%) cases, whereas benign prostate tissue exhibited weak immunostaining. Depletion of SMYD3 by siRNA or shRNA inhibited PC cell proliferation (72 hours relative to 24 hours: control shRNA vs SMYD3 shRNA 1: mean fold change = 2.76 vs 1.68; difference = 1.08; 95% confidence interval = 0.78 to 1.38, P < .001), colony formation, cell migration, invasion, and xenograft tumor formation. Two functional SMYD3-binding motifs were identified in the AR promoter region. SMYD3 promotes prostate tumorigenesis and mediates epigenetic upregulation of AR expression.


A balanced approach to falls prevention: Application in the real world.
Falls place a heavy burden on the health system, impacting on an individual's quality of life, often resulting in a fear of falling, reduction in independence and at times admission to residential care. This study aimed to determine health professionals' confidence in discussing falls prevention strategies, topics discussed and the barriers and enablers to falls prevention discussions with clients aged 60 years and over. A cross-sectional self-complete online survey was undertaken with a sample of health professionals (n = 191) who had engaged in the services of the Stay On Your Feet® programs delivered by the Injury Matters in Western Australia (WA). The majority of participants were physiotherapists (25.7%), registered nurses (17.8%) and occupational therapists (11%) located in metropolitan (56%) and regional (44%) WA. Most health professionals (80.2%) were "highly" confident discussing falls prevention strategies. Discussion of falls prevention included the benefits of strength and balance exercises (83%), eating a healthy diet (78.7%), regular eyesight checks (64.5%), reviewing medications (54.8%) and exposure to sunlight (50.3%). The main enablers to falls prevention were knowledge (89.7%), skills to identify (77.7%) and implement (66.3%) falls prevention strategies, and access to printed resources (74.9%), while the main barrier was appointment times (14.6%). Health professionals' indicated that they are confident in discussing falls prevention strategies, and although a range of falls prevention strategies were discussed, limited attention was directed at the pharmacists' review of medications, eyesight checks and increasing vitamin D levels. SO WHAT?: Health professionals are discussing falls prevention strategies with their clients. A more multifaceted approach should be encouraged with an emphasis on all prevention strategies.


Heat shock protein cognate 70-4 and an E3 ubiquitin ligase, CHIP, mediate plastid-destined precursor degradation through the ubiquitin-26S proteasome system in Arabidopsis.
Plastid-targeted proteins pass through the cytosol as unfolded precursors. If proteins accumulate in the cytosol, they can form nonspecific aggregates that cause severe cellular damage. Here, we demonstrate that high levels of plastid precursors are degraded through the ubiquitin-proteasome system (UPS) in Arabidopsis thaliana cells. The cytosolic heat shock protein cognate 70-4 (Hsc70-4) and E3 ligase carboxy terminus of Hsc70-interacting protein (CHIP) were highly induced in plastid protein import2 plants, which had a T-DNA insertion at Toc159 and showed an albino phenotype and a severe defect in protein import into chloroplasts. Hsc70-4 and CHIP together mediated plastid precursor degradation when import-defective chloroplast-targeted reporter proteins were transiently expressed in protoplasts. Hsc70-4 recognized specific sequence motifs in transit peptides and thereby led to precursor degradation through the UPS. CHIP, which interacted with Hsc70-4, functioned as an E3 ligase in the Hsc70-4-mediated protein degradation. The physiological role of Hsc70-4 was confirmed by analyzing Hsc70-4 RNA interference plants in an hsc70-1 mutant background. Plants with lower Hsc70 levels exhibited abnormal embryogenesis, resulting in defective seedlings that displayed high levels of reactive oxygen species and monoubiquitinated Lhcb4 precursors. We propose that Hsc70-4 and CHIP mediate plastid-destined precursor degradation to prevent cytosolic precursor accumulation and thereby play a critical role in embryogenesis.


Cephalocele: report of 55 cases over 8 years.
Cephalocele is a central nervous system (CNS) birth defect. Various CNS and extra-CNS anomalies, as well as prognostic factors have been reported with cephalocele. The aim of this study was to discuss prognostic factors and current possible theories explaining associated anomalies seen in a series of 55 patients with cephalocele. A retrospective study was performed using the records of 55 children with cephalocele at the Children's Hospital Medical Center in Tehran, Iran, from October 2000 through October 2008. Patients' sex, age at the operation time, characteristics of the lesion including location, size, cerebrospinal fluid leakage, radiological assessments and intraoperative findings (sac contents), intracranial and extracranial associated anomalies, and the last situation of the children were reviewed. A genetic role can be proposed while a female predominance is seen in our results as well as in other reports. CNS and extra-CNS anomalies, as well as several genetic syndromes are not explicable as a causal consequence of cephalocele and the probability of a mere coincidence cannot be ruled out; therefore, we propose that the combination of these anomalies is rather a low-frequency association. Ventriculomegaly was the only poor prognostic determinant in our study, which can compel more severe neuroradiologic studies in such patients as a reasonable prognostic evaluation.


Detecting removable surface contamination.
Although surveying for radioactive contamination by wiping surfaces is the norm, this practice can be highly variable and may be inefficient for detecting low-energy beta emitters. Relying on wipe testing may likewise be an inefficient use of personnel and may seriously underrepresent the amount of contamination present. In general practice, it is better to clean and, where applicable, renew surfaces regularly as part of standard operating protocols and work practices.


Role of Peer Coaching in Transmitting the Benefits of Leader Coaching.
Drawing on social information processing theory, the present study examines how and when leader coaching can be beneficial for team performance. Based on a sample of 58 teams from a sanitary product company in China, we found that peer coaching served as a mediator linking leader coaching and team performance. Moreover, the team individualistic/collectivism value moderated the first-stage relationship that the relationship between leader coaching and peer coaching was more positive when the team individualism value was low, but not significant when the team individualism value was high; while team task interdependence moderated the second-stage relationship that the relationship between peer coaching and team performance was more positive when the team task interdependence was high, but not significant when it was low. The findings enrich our understandings of the effectiveness of leader coaching behavior by uncovering the theoretical mechanism and boundary conditions. The study also provides important implications for coaching practice in organizations.


Formation of dihydronaphthalenes via organocatalytic enatioselective Michael-aldol cascade reactions with arylalkanes.
An organocatalytic highly enantioselective Michael-aldol cascade access to valuable chiral dihydronaphthalenes has been realized. Notably, the strategy via activation of nucleophilic alkyl chains by introducing nitro, chloro, or CF3 group(s) at the ortho- and/or para-position(s) on an aromatic ring renders them readily deprotonated to produce highly reactive nulecophilic species in the cascade process under mild conditions.


[Antibodies to anticoagulants in rheumatic autoimmune diseases].
The systemic lupus erythematosus (SLE) and the rheumatoid arthritis (RA) as the classic autoimmune diseases exhibit a great number of autoantibodies. Some of them are anticoagulants. Besides inactivating inhibitors against single coagulation factors interfering anticoagulants are known, belonging to the group of anti-phospholipid antibodies and detected as the lupus anticoagulants or anticardiolipin antibodies. Anti-phospholipid antibodies 184 patients with SLE or RA had been checked for. An enzyme immuno assay was used for detection of the anti-cardiolipin antibodies. The relations between occurrence of the anti-cardiolipin antibodies and vascular processes as well as other immunologic parameters had been tested for clinical relevancy.


[Surgical treatment of acute ascending dissection--a simplified operative method].
Primary anastomosis for acute ascending aortic dissection was performed in 8 patients. Primary anastomosis included resection of the intimal tear where applicable, a circumferential suture line in the ascending aorta at the site of the tear, and wrapping of the anastomosis of the ascending aorta with Dacron vascular prosthesis. The aortic valve was resuspended in 1 of 6 patients associated with aortic regurgitation. In 4 patients, aortic regurgitation disappeared postoperatively. Two patients show minor non-progressive valve regurgitation. Two of 8 patients died early postoperatively. There was no late death and dilatation of the aortic root in the follow-up period of mean 27 months. On the basis of these results, we believe that primary anastomosis is a simpler and safer operative method for acute dissection of the ascending aorta.


Detection of inflammation with 99mTC-HMPAO labelled leucocytes.
20 patients were studied with 99mTcHMPAO labelled leucocytes for detection of inflammation. 14 patients had positive uptake. 6 patients were examined also with 67Ga-citrate and 5 with 99mTc-nanocolloid. The 99mTc-HMPAO images were superior to other methods. Abscesses, osteitis, inflammatory bowel disease and graft infection were positive. Abscesses were positive at 30 min images and became more positive at 4 h. The 99mTc-HMPAO labelled leucocyte scan can be used also to follow up healing of inflammation.


Recent Advances of Magnetic Nanomaterials in Bone Tissue Repair.
The magnetic field has been proven to enhance bone tissue repair by affecting cell metabolic behavior. Magnetic nanoparticles are used as biomaterials due to their unique magnetic properties and good biocompatibility. Through endocytosis, entering the cell makes it easier to affect the physiological function of the cell. Once the magnetic particles are exposed to an external magnetic field, they will be rapidly magnetized. The magnetic particles and the magnetic field work together to enhance the effectiveness of their bone tissue repair treatment. This article reviews the common synthesis methods, the mechanism, and application of magnetic nanomaterials in the field of bone tissue repair.


[Exploring Patient Motives to Use Emergency Departments for Non-urgent Conditions: A Qualitative Study].
Background: The increasing utilization of Emergency Departments (ED) by outpatients with acute but non-urgent conditions contributes to ED crowding. This study aims to explore the motives of patients categorized as non-urgent for visiting the ED. Methods: A qualitative study based on semi-structured interviews was conducted at 2 ED's at Charité Berlin. A total of 40 patients categorized as non-urgent were interviewed. Data were analyzed using Qualitative Content Analysis. Results: In addition to unavailable appointments or having to wait a long time for an appointment with general practitioners and specialists, patients stated better time-flexibility, the University Hospital's quality of care and the availability of multidisciplinary care as reasons to seek medical care in the ED. Because of the 24/7 availability of EDs, some patients seem to make little effort to seek an appointment with a GP or a specialist outside the hospital. Conclusion: Our interview data indicate an independent function of EDs in outpatient care. It must be assumed that even a full coverage of service guarantee by the association of statuary health insurance physicians would not reduce ED utilization to cases of medical urgency only. To ensure sustainable medical quality for urgent as well as non-urgent medical care seekers, EDs need appropriate resources to cover the demand.


The relationship between cranial metric and nonmetric traits in the rhesus macaques from Cayo Santiago.
This study addresses the relationship between cranial metric variables and nonmetric traits using the skeletal sample of rhesus macaques from Cayo Santiago. Discriminant function analysis is used to study the metric differences between macaque crania grouped according to the presence or absence of nine nonmetric traits. The computation of total structure coefficients from the discriminant function analyses provides information regarding how closely each metric variable is related to the discriminant functions derived. Total structure coefficients have not been used previously in the study of the relationship between metric and nonmetric traits. The results of the analysis are interpreted using an explicit approach to cranial morphogenesis-functional cranial analysis. It is concluded that the relationship between cranial metric and nonmetric traits is explicable in terms of a common developmental pathway shared by the two types of traits. Identification of the specific etiology of nonmetric traits depends on future anatomical studies or organisms throughout the period of nonmetric trait development.


A Qualitative Study of Substance use during Pregnancy: Implications for Reproductive Healthcare in Western Kenya.
Women who use alcohol and drugs are often in their childbearing years, creating a need for integrated substance abuse and reproductive health services. However, our understanding of the social context and drivers of substance use during pregnancy, particularly in developing countries, is limited and largely unaddressed in clinical care. Our qualitative research explored the reproductive health of women of childbearing age who inject drugs and its implications for healthcare in Kisumu, Kenya. We used in-depth, semi-structured qualitative interviews with 17 women who inject drugs to explore reproductive health topics including knowledge, practices, and clinical interactions related to substance use during pregnancy. All but one woman had a prior pregnancy and two were pregnant during our study. Alcohol and drug use was prevalent throughout pregnancy, often described as a coping mechanism for stress. Women received mixed advice from family and social contacts regarding alcohol use during pregnancy, leading to differing perceptions of its health effects. Healthcare providers infrequently screened women for alcohol or drug use. Our analysis highlights the need for culturally appropriate alcohol and drug screening and counseling to be included in integrated reproductive health services in western Kenya.


Relationship of preoperative neutrophil lymphocyte ratio with prognosis in gastrointestinal stromal tumors.
Gastrointestinal stromal tumors are believed to play a role in immunosuppression with their local effect. In some cancers with associated inflammation, an increased pretreatment neutrophil lymphocyte ratio is considered as an indicator of poor prognosis. The aim of our study was to assess the relationship of increased blood neutrophil lymphocyte ratio with disease prognosis in patients with gastrointestinal stromal tumors. The data of 78 patients who underwent surgery with the diagnosis of primary gastrointestinal stromal tumor in our clinic were evaluated retrospectively. The preoperative neutrophil lymphocyte ratio in the peripheral blood was determined. The neutrophil lymphocyte ratio and its relationship with tumor risk and prognosis were compared. The data were evaluated by Pearson's correlation analysis and the Welch ANOVA test. The preoperative neutrophil lymphocyte ratio was significantly increased in the high-risk groups (p<0.05). An increased preoperative neutrophil lymphocyte ratio was associated with shorter survival (r=-0.32, p=0.009). In addition, an increase in the neutrophil lymphocyte ratio was associated with an increase in the mitotic activity of the tumor (r=-0.364, p=0.025). The preoperative neutrophil lymphocyte ratio in gastrointestinal stromal tumors can be used as an indicator of high-risk tumors and poor prognosis.


Exploiting the p53 Pathway for Therapy.
The excitement around the entry into the clinic of the first generation of p53-specific drugs has become muted as the hoped-for dramatic clinical responses have not yet been seen. However, these pioneer molecules have become exceptionally powerful tools in the analysis of the p53 pathway and, as a result, a whole spectrum of new interventions are being explored. These include entirely novel and innovative approaches to drug discovery, such as the use of exon-skipping antisense oligonucleotides and T-cell-receptor-based molecules. The extraordinary resources available to the p53 community in terms of reagents, models, and collaborative networks are generating breakthrough approaches to medicines for oncology and also for other diseases in which aberrant p53 signaling plays a role.


[Muscular fitness and cardiometabolic risk factors among Colombian young adults].
To determine the influence of muscular fitness (MF) on cardiometabolic risk factors in young adult. A total of 172 men (age 19.7±2.4 years; weight 65.5±10.7 kg; BMI 22.6±2.8 kg•m(-1)) were invited to participate in the study. They had no indication of cardiometabolic problems, as evaluated by clinical interview. MF was measured by isometric handgrip (dynamometer). The handgrip strength was divided by body mass was used in further analysis. Lower and higher MF values are represented by the first and fourth quartiles, respectively. A lipid-metabolic cardiovascular risk index was derived from the levels of triglycerides, low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), and glucose. Adiposity index were assessed by measuring, waist circumference (WC), body adiposity index (BAI), body mass index (BMI) and fat mass (%). After adjustment for age, BMI and WC, inverse association was observed between fat mass, WC, cholesterol, HDL-c, LDL-c and MF (p<0.05). In addition, subjects with low handgrip strength/kg body mass(Q1), shower high levels of fat mass, WC, cholesterol, HDL-c and LDL-c (p<0.05 linear). Lasted, a linear relationship was also observed between the MF/kg and the lipid-metabolic index (p<0.05). In Colombian young adult poorer hand-grip strength/kg body mass were associated with worse metabolic risk factors and adiposity index. Increasing muscle strength could be an appropriate strategy to achieve favorable changes in metabolic risk profile.


New-onset cardiac rhabdomyoma beyond infancy in a patient with tuberous sclerosis complex.
Cardiac rhabdomyomas in patients with tuberous sclerosis complex are usually detected antenatally or during infancy, with subsequent stabilisation or spontaneous regression. Development of a new cardiac rhabdomyoma beyond infancy is very rare. We report a male child who needed resection of a large rhabdomyoma in neonatal life, and then developed a new-onset rhabdomyoma at 2 years of age in a different location, needing another resection. Routine surveillance for cardiac rhabdomyomas in asymptomatic patients with tuberous sclerosis is essential.


Endoscopic applications of optical coherence tomography.
We report results of application of our endoscopic optical coherence tomography (EOCT) system in clinical experiments to image human internal organs. Based on the experience of studying more than 100 patients, we make first general conclusions on the place and capabilities of this method in diagnosing human mucous membranes. It is demonstrated that EOCT can serve for several clinical purposes such as performing directed biopsy, monitoring functional states of human body, guiding surgical and other treatments and monitoring post-operative recovery processes. We show that applications of OCT are more informative in the case of internal organs covered by epithelium separated from underlying stroma by a smooth basal membrane and therefore concentrate on the results of the EOCT study of three internal organs, namely of larynx, bladder, and uterine cervix. Finally, we report first examination of internal organs in abdomen with the use of laparoscopic OCT.


The protein kinase C-beta inhibitor, ruboxistaurin, for the treatment of diabetic microvascular complications.
The potential for addressing the underlying biological abnormalities in diabetes has eluded most investigators because of the complex mechanisms underlying the effects of diabetes on the pathogenesis of the complications. Although macrovascular complications, such as myocardial infarction, stroke and gangrene, are only partially attributable to hyperglycaemia and its attendant effects, the microvascular complications including retinopathy, nephropathy and neuropathy are directly related to the degree of hyperglycaemia. In controlled trials, a 22-34% reduction in one of these side effects was achieved for every 1% reduction in glycosylated haemoglobin. Theoretically, it should be feasible to eliminate these complications in a perfect world. However, achieving euglycaemia is nearly impossible and there is increasing data to suggest that it may be an elusive target with ever lower levels being implicated in the pathogenesis of microvascular disease and there is a price to be paid of hypoglycaemia if further intensification is pursued. A logical argument would be to block pathways that are activated by hyperglycaemia. A major pathway implicated is the activation of protein kinase C-beta in all of the targeted tissues, and there is animal data to support the notion that blocking this pathway can reverse or abrogate the untoward effects of diabetes. The possible role of the protein kinase C-beta inhibitor, ruboxistaurin, in animal studies and the recently reported clinical studies to place in perspective a possible addition to the therapeutic armamentarium of the imperfect world of diabetes control will be reviewed.


Loss of heparan sulfate in the niche leads to tumor-like germ cell growth in the Drosophila testis.
The stem cell niche normally prevents aberrant stem cell behaviors that lead to cancer formation. Recent studies suggest that some cancers are derived from endogenous populations of adult stem cells that have somehow escaped from normal control by the niche. However, the molecular mechanisms by which the niche retains stem cells locally and tightly controls their divisions are poorly understood. Here, we demonstrate that the presence of heparan sulfate (HS), a class glygosaminoglycan chains, in the Drosophila germline stem cell niche prevents tumor formation in the testis. Loss of HS in the niche, called the hub, led to gross changes in the morphology of testes as well as the formation of both somatic and germline tumors. This loss of hub HS resulted in ectopic signaling events in the Jak/Stat pathway outside the niche. This ectopic Jak/Stat signaling disrupted normal somatic cell differentiation, leading to the formation of tumors. Our finding indicates a novel non-autonomous role for niche HS in ensuring the integrity of the niche and preventing tumor formation.


Effect of a medical-surgical practice and certification review course on clinical nursing practice.
The purpose of this study was to describe the effects of participation in a medical-surgical certification and practice review course on the participants' clinical nursing practice. A descriptive survey was mailed to 119 nurses 4 months after the completion of the 2005 course. The majority responding agreed that participation in the course had a positive effect on their self-confidence, competence, leadership, and initiative. The written clinical examples demonstrated the efficacy of the course in the domains of knowledge acquisition and validation, enhancement of confidence, and the ability to contribute to collegial discussions. These results demonstrate successful achievement of the ultimate goal of staff education: to see nurses translate newly acquired knowledge into practice.


Team-Based Hypertension Management to Improve Blood Pressure Control.
Hypertension is the most common condition seen in primary care, occurring in 1 in 3 adults in the United States. The patient-centered medical home provides an opportunity for proactive, team-based care of hypertension. The purpose of this pilot study was to measure the effectiveness of a team-based approach to blood pressure management in a busy, primary care setting. Using panel management within 2 primary care clinics, a cohort of patients with blood pressures >160/100 mm Hg, was identified. The patients at 1 clinic were contacted by the primary care team and offered multiple interventions aimed at improving blood pressure control; including discussion of medication compliance, medication titration, home blood pressure monitoring, nutritional counseling, and motivational interviewing. The change in blood pressure for these patients at 4 months was compared to a parallel primary care clinic within the same medical center whose patients were treated with usual primary care. A total of 350 and 315 patients were included in the intervention and usual care cohorts, respectively. At 4 months, the decrease of systolic blood pressure in the intervention group was significantly greater than in the usual care group (15.6 vs 9.9 mm Hg; P < .001). Sixty-two percent of patients in the intervention group had lower systolic blood pressures post intervention, compared with 41% of usual care patients (P < .001). Reduction in diastolic blood pressure occurred in 54% of intervention patients, compared with 37% of usual care patients (P < .001). Our findings demonstrate the effectiveness of a team-based approach to blood pressure management. This can provide a framework for implementation of team-based care for hypertension in the patient-centered medical home.


A novel paradigm of fatty acid beta-oxidation exemplified by the thioesterase-dependent partial degradation of conjugated linoleic acid that fully supports growth of Escherichia coli.
An alternative pathway of beta-oxidation for unsaturated fatty acids was studied in Escherichia coli. 9- cis,11- trans-Octadecadienoic acid (conjugated linoleic acid), a potential substrate of this pathway, was shown to support growth of E. coli in the absence of any other carbon source. The identification of 3,5-dodecadienoic acid in the growth medium revealed the partial beta-oxidation of conjugated linoleic acid to 3,5-dodecadienoyl-CoA, which was hydrolyzed to 3,5-dodecadienoic acid and released from cells. The involvement of acyl-CoA thioesterases in this process was evaluated by determining the substrate specificity of thioesterase II and comparing it with that of a novel thioesterase (thioesterase III) and by assessing mutant strains devoid of one or both of these thioesterases for growth on conjugated linoleic acid. Both thioesterases were highly active with 3,5-dodecadienoyl-CoA as substrate. A deficiency of either thioesterase decreased the growth rate of cells on conjugated linoleic acid but not on palmitic acid. The absence of both thioesterases reduced the cellular growth in a cumulative manner but did not abolish it. It is concluded that thioesterases II and III and at least one other thioesterase function in the partial degradation of conjugated linoleic acid via the thioesterase-dependent pathway of beta-oxidation, which provides all energy and carbon precursors required for the growth of E. coli.


Energy storage and the evolution of population dynamics.
We explore the mutual dependence of life history evolution and population dynamics by modeling a structured rotifer population that preys on a dynamic food supply. We focus on the ecological role of energy storage. A physiologically based submodel describes how individual predators allocate assimilated energy among growth, reproduction, and storage. We use invasibility analyses to predict evolutionary stable strategies for energy allocation. Various proxy measures of fitness based on measurable biological quantities, such as average population size or average per-capita fecundity, fail to predict evolutionary stable strategies. The predicted strategies indicate that selection strongly favors storage allocation for juveniles, but only for adults when prey densities are high. With the evolution of energy storage, population dynamics can shift from aperiodic to stable cycles without any need to invoke group selection.


Legionella pneumophila: an aquatic microbe goes astray.
Legionella pneumophila is naturally found in fresh water were the bacteria parasitize within protozoa. It also survives planctonically in water or biofilms. Upon aerosol formation via man-made water systems, L. pneumophila can enter the human lung and cause a severe form of pneumonia, called Legionnaires' disease. The pathogenesis of Legionnaires' disease is largely due to the ability of L. pneumophila to invade and grow within macrophages. An important characteristic of the intracellular survival strategy is the replication within the host vacuole that does not fuse with endosomes or lysosomes. In recent times a great number of bacterial virulence factors which affect growth of L. pneumophila in both macrophages and protozoa have been identified. The ongoing Legionella genome project and the use of genetically tractable surrogate hosts are expected to significantly contribute to the understanding of bacterium-host interactions and the regulation of virulence traits during the infection cycle. Since person-to-person transmission of legionellosis has never been observed, the measures for disease prevention have concentrated on eliminating the pathogen from water supplies. In this respect detection and analysis of Legionella in complex environmental consortia become increasingly important. With the availability of new molecular tools this area of applied research has gained new momentum.


[Percezione e soddisfazione degli studenti in Ostetricia al primo anno di tirocinio clinico: studio osservazionale multicentrico].
To explore the first year midwifery students' clinical learning experience and satisfaction; to analyse the association between students' satisfaction and individual motivation. The multicentre cross-sectional study was carried out in four Italian midwifery degree courses. A convenience sample of 61 students filled out the Italian version of the "Clinical Learning Environment and Supervision plus Nurse Teacher (CLES+T) scale" after the conclusion of their first clinical placement. The mean values of the main sub-dimensions of CLES+T varied from 3.53 (peda- gogical atmosphere) to 3.08 (supervisory relationship). Students (68.9%) were mainly sati- sfied with their clinical placement. With regard to individual motivation, 27 students (44.3%) were motivated at the beginning of the clinical placement, and 31 students (50.8%) were highly motivated. Highly motivated students showed higher satisfaction levels (␣2 = 11,712, p = 0.019). The findings expand knowledge on the first year midwifery students' clinical learning experience Moreover, the results showed an association between initial student moti- vation and satisfaction that should be investigated through further multicenter studies.


PHOTORECEPTOR DAMAGE IN DIABETIC CHOROIDOPATHY.
To investigate the relationship between choriocapillaris (CC) hypoperfusion and photoreceptor alterations in eyes with nonproliferative diabetic retinopathy (NPDR). In this prospective, observational, case-control study, 30 eyes (30 patients) with NPDR and 30 healthy eyes from 30 controls were enrolled at the University G. d'Annunzio, Chieti-Pescara, Italy. This study cohort underwent an ophthalmologic examination, including optical coherence tomography and optical coherence tomography angiography. The main outcome measures were as follows: 1) "normalized" reflectivity of en face image segmented at the ellipsoid zone level, which was calculated to quantify the photoreceptor damage, and 2) CC perfusion density. Secondary outcome measures were as follows: 1) superficial retinal capillary plexus (SCP), intermediate retinal capillary plexus (ICP), and deep retinal capillary plexus (DCP) perfusion density (based on the area of vessels); 2) SCP, ICP, and DCP vessel length density (based on a map with vessels of 1-pixel width); and 3) SCP, ICP, and DCP vessel diameter. Mean ± SD age was 58.9 ± 11.1 years (range 38-79 years) in the NPDR group and 61.7 ± 11.3 years (range 39-87 years) in the control group (P > 0.05 for all the comparisons). Compared with controls, NPDR eyes displayed a lower "normalized" reflectivity (0.96 ± 0.25 in controls and 0.73 ± 0.19 in the NPDR group, P < 0.0001). Moreover, the NPDR group was characterized by an impaired perfusion in both the retinal and choroidal vasculature. In multiple regression analysis, ellipsoid zone "normalized" reflectivity displayed a significant direct association with CC perfusion density in patients with NPDR (P = 0.025 and P = 0.476, in NPDR and controls, respectively). Eyes with NPDR are affected by macular hypoperfusion and photoreceptor damage, the latter investigated as ellipsoid zone "normalized" reflectivity. The diabetic choroidopathy seems to be strongly associated with photoreceptor damage.


Branchial O(2) chemoreceptors in Nile tilapia Oreochromis niloticus: Control of cardiorespiratory function in response to hypoxia.
This study examined the distribution and orientation of gill O(2) chemoreceptors in Oreochromis niloticus and their role in cardiorespiratory responses to graded hypoxia. Intact fish, and a group with the first gill arch excised (operated), were submitted to graded hypoxia and their cardiorespiratory responses (oxygen uptake - V˙O(2) , breathing frequency - fR, ventilatory stroke volume - VT, gill ventilation - V˙G, O(2) extraction from the ventilatory current - EO(2) , and heart rate - fH) were compared. Their responses to bolus injections of NaCN into the bloodstream (internal) or ventilatory water stream (external) were also determined. The V˙O(2) of operated fish was significantly lower at the deepest levels of hypoxia. Neither reflex bradycardia nor ventilatory responses were completely abolished by bilateral excision of the first gill arch. EO(2) of the operated group was consistently lower than the intact group. The responses to internal and external NaCN included transient decreases in fH and increases in fR and Vamp (ventilation amplitude). These cardiorespiratory responses were attenuated but not abolished in the operated group, indicating that chemoreceptors are not restricted to the first gill arch, and are sensitive to oxygen levels in both blood and water.


Construction of a 550 kb BAC contig spanning the genomic region containing the apple scab resistance gene Vf.
A positional cloning project was started in apple with the aim of isolating the Vf resistance gene of Malus floribunda 821. Vf confers resistance against apple scab, the most important disease in apple orchards. A chromosome walk starting from two molecular markers (M18-CAPS and AM19-SCAR) flanking Vf was performed, using a bacterial artificial chromosome (BAC) library containing inserts of the cultivar Florina, which is heterozygous for Vf. Thirteen BAC clones spanning the region between the two markers were identified in nine chromosome walking steps. The size of the resulting contig is approximately 550 kb. In order to map the Vf region in more detail, we analyzed over 2000 plants from different populations segregating for Vf with markers produced from BAC end sequences. In this way, we were able to restrict the possible location of the Vf gene to a minimum of five clones spanning an interval of approximately 350 kb.


Malaria Surveillance - United States, 2018.
Malaria in humans is caused by intraerythrocytic protozoa of the genus Plasmodium. These parasites are transmitted by the bite of an infective female Anopheles species mosquito. Most malaria infections in the United States and its territories occur among persons who have traveled to regions with ongoing malaria transmission. However, among persons who have not traveled out of the country, malaria is occasionally acquired through exposure to infected blood or tissues, congenital transmission, nosocomial exposure, or local mosquitoborne transmission. Malaria surveillance in the United States and its territories provides information on its occurrence (e.g., temporal, geographic, and demographic), guides prevention and treatment recommendations for travelers and patients, and facilitates rapid transmission control measures if locally acquired cases are identified. This report summarizes confirmed malaria cases in persons with onset of illness in 2018 and trends in previous years. Malaria cases diagnosed by blood smear microscopy, polymerase chain reaction, or rapid diagnostic tests are reported to local and state health departments through electronic laboratory reports or by health care providers or laboratory staff members directly reporting to CDC or health departments. Case investigations are conducted by local and state health departments, and reports are transmitted to CDC through the National Malaria Surveillance System (NMSS), the National Notifiable Diseases Surveillance System (NNDSS), or direct CDC clinical consultations. CDC reference laboratories provide diagnostic assistance and conduct antimalarial drug resistance marker testing on blood specimens submitted by health care providers or local or state health departments. This report summarizes data from the integration of all cases from NMSS and NNDSS, CDC clinical consultations, and CDC reference laboratory reports. CDC received reports of 1,823 confirmed malaria cases with onset of symptoms in 2018, including one cryptic case and one case acquired through a bone marrow transplant. The number of cases reported in 2018 is 15.6% fewer than in 2017. The number of cases diagnosed in the United States and its territories has been increasing since the mid-1970s; the number of cases reported in 2017 was the highest since 1972. Of the cases in 2018, a total of 1,519 (85.0%) were imported cases that originated from Africa; 1,061 (69.9%) of the cases from Africa were from West Africa, a similar proportion to what was observed in 2017. Among all cases, P. falciparum accounted for most infections (1,273 [69.8%]), followed by P. vivax (173 [9.5%]), P. ovale (95 [5.2%]), and P. malariae (48 [2.6%]). For the first time since 2008, an imported case of P. knowlesi was identified in the United States and its territories. Infections by two or more species accounted for 17 cases (<1.0%). The infecting species was not reported or was undetermined in 216 cases (11.9%). Most patients (92.6%) had symptom onset <90 days after returning to the United States or its territories from a country with malaria transmission. Of the U.S. civilian patients who reported reason for travel, 77.0% were visiting friends and relatives. Chemoprophylaxis with antimalarial medications are recommended for U.S. residents to prevent malaria while traveling in countries where it is endemic. Fewer U.S. residents with imported malaria reported taking any malaria chemoprophylaxis in 2018 (24.5%) than in 2017 (28.4%), and adherence was poor among those who took chemoprophylaxis. Among the 864 U.S. residents with malaria for whom information on chemoprophylaxis use and travel region were known, 95.0% did not adhere to or did not take a CDC-recommended chemoprophylaxis regimen. Among 683 women with malaria, 19 reported being pregnant. Of these, 11 pregnant women were U.S. residents, and one of whom reported taking chemoprophylaxis to prevent malaria but her adherence to chemoprophylaxis was not reported. Thirty-eight (2.1%) malaria cases occurred among U.S. military personnel in 2018, more than in 2017 (26 [1.2%]). Among all reported malaria cases in 2018, a total of 251 (13.8%) were classified as severe malaria illness, and seven persons died from malaria. In 2018, CDC analyzed 106 P. falciparum-positive and four P. falciparum mixed species specimens for antimalarial resistance markers (although certain loci were untestable in some specimens); identification of genetic polymorphisms associated with resistance to pyrimethamine were found in 99 (98.0%), to sulfadoxine in 49 (49.6%), to chloroquine in 50 (45.5%), and to mefloquine in two (2.0%); no specimens tested contained a marker for atovaquone or artemisinin resistance. The importation of malaria reflects the overall trends in global travel to and from areas where malaria is endemic, and 15.6% fewer cases were imported in 2018 compared with 2017. Of imported cases, 59.3% were among persons who had traveled from West Africa. Among U.S. civilians, visiting friends and relatives was the most common reason for travel (77.1%). The best way for U.S. residents to prevent malaria is to take chemoprophylaxis medication before, during, and after travel to a country where malaria is endemic. Adherence to recommended malaria prevention strategies among U.S. travelers would reduce the number of imported cases. Reported reasons for nonadherence include prematurely stopping after leaving the area where malaria was endemic, forgetting to take the medication, and experiencing a side effect. Health care providers can make travelers aware of the risks posed by malaria and incorporate education to motivate them to be adherent to chemoprophylaxis. Malaria infections can be fatal if not diagnosed and treated promptly with antimalarial medications appropriate for the patient's age, pregnancy status, medical history, the likely country of malaria acquisition, and previous use of antimalarial chemoprophylaxis. Antimalarial use for chemoprophylaxis and treatment should be determined by the CDC guidelines, which are frequently updated. In April 2019, intravenous (IV) artesunate became the first-line medication for treatment of severe malaria in the United States and its territories. Artesunate was approved by the Food and Drug Administration (FDA) in 2020 and is commercially available (Artesunate for Injection) from major U.S. drug distributors (https://amivas.com). Stocking IV artesunate locally allows for immediate treatment of severe malaria once diagnosed and provides patients with the best chance of a complete recovery and no sequelae. With commercial IV artesunate now available, CDC will discontinue distribution of non-FDA-approved IV artesunate under an investigational new drug protocol on September 30, 2022. Detailed recommendations for preventing malaria are online at https://www.cdc.gov/malaria/travelers/drugs.html. Malaria diagnosis and treatment recommendations are also available online at https://www.cdc.gov/malaria/diagnosis_treatment. Health care providers who have sought urgent infectious disease consultation and require additional assistance on diagnosis and treatment of malaria can call the Malaria Hotline 9:00 a.m.-5:00 p.m. Eastern Time, Monday-Friday, at 770-488-7788 or 855-856-4713 or after hours for urgent inquiries at 770-488-7100. Persons submitting malaria case reports (care providers, laboratories, and state and local public health officials) should provide complete information because incomplete reporting compromises case investigations and public health efforts to prevent future infections and examine trends in malaria cases. Molecular surveillance of antimalarial drug resistance markers enables CDC to track, guide treatment, and manage drug resistance in malaria parasites both domestically and globally. A greater proportion of specimens from domestic malaria cases are needed to improve the completeness of antimalarial drug resistance analysis; therefore, CDC requests that blood specimens be submitted for any case of malaria diagnosed in the United States and its territories.


Effect of nutrition on testicular growth and plasma concentrations of gonadotrophins, testosterone and insulin-like growth factor I (IGF-I) in pubertal male Soay sheep.
Nutritional effects on puberty were studied in Soay rams. Testicular growth is initiated at birth in April and testes reach maximum size in October. Groups of eight lambs were fed for 18 weeks, starting in August, a ration that restricted growth (Group R), the same diet ad libitum (Group F), or a restricted diet for 8 weeks followed by ad libitum feeding (Group R/F). Seasonal increases of plasma FSH, testis size, sexual skin flush and plasma testosterone occurred with similar timing but reduced magnitude in Group R compared with Group F lambs. Testis size and sexual skin flush peaked in all groups at 11 weeks (30 October); the testes of Group F animals were larger before the peak, but similar in size thereafter, compared with testes from Group R/F, and larger throughout the experimental period than testes from Group R. Plasma testosterone was higher in Group F than in Group R lambs from 7 to 17 weeks, but in Group R/F was similar to Group R before 10 weeks (23 October) and similar to Group F thereafter. Testis size, plasma testosterone, plasma insulin-like growth factor I (IGF-I) and liveweight were positively correlated. Ad libitum feeding in August-September (Group F) stimulated increased plasma FSH and LH above values for Group R, but ad libitum feeding initiated in October did not affect gonadotrophin concentrations (Group R/F). Therefore, the effects of improved nutrition on the hypothalamo-pituitary axis, which may have been mediated by circulating IGF-I, were season- or age-dependent, and those on the testes included direct stimulation, independent of changes in gonadotrophin concentrations. Nutrition modified the intensity, but not the timing, of peak pubertal reproductive activation.


Antimicrobial effect in vitro of chlorhexidine and calcium hydroxide impregnated gutta-percha points.
The aim of this study was to evaluate the antimicrobial activity of points containing antiseptics used for temporary obturation in endodontics. Points containing calcium hydroxide (Roeko and Hygienic), and chlorhexidine (Roeko) were tested and gutta-percha points served as control (Meta Dental Corp.). The following microorganisms were studied: Streptococcus mutans (Sm), Enterococcus faecalis (Ef), Staphylococcus aureus (Sta), Candida albicans (Ca), Fusobacterium nucleatum (Fn) ATCC 25586, Porphyromonas gingivalis (Pg) ATCC 33277, and Prevotella intermedia (Pi) ATCC 25611. The experiments were organized in three stages: 1st stage: one point of each kind was placed on agar plates previously seeded with microorganisms. 2nd stage: Another group of points was immersed in broth for 24 hours and placed on the seeded agar. Samples were then incubated at 37 degrees in the conditions of oxygen and for the time required by each microorganism. The zones of bacterial inhibition around each point were measured. The pH values of the broths were recorded. 3rd stage: the immersion broths were inoculated with suspensions of microorganisms, incubated, seeded on plates by dissemination and incubated. CFU counts were performed. points containing chlorhexidine showed inhibition zones with every microorganism in the 1st stage and, in the 2nd stage, with most of the microorganisms studied, except for Fn and Pi. Calcium hydroxide containing points did not inhibit any of the microorganisms assessed. Broth pH values did not exhibit any changes. CFU counts of the broths in which chlorhexidine points had been immersed showed total inhibition for all the microorganisms. The differences between materials were statistically significant (p<0.05) (ANOVA). In the conditions of this study, chlorhexidine-containing points proved to be effective against most of the tested strains.


Sex determination through X-Y heterogamety in Salix nigra.
The development of non-recombining sex chromosomes has radical effects on the evolution of discrete sexes and sexual dimorphism. Although dioecy is rare in plants, sex chromosomes have evolved repeatedly throughout the diversification of angiosperms, and many of these sex chromosomes are relatively young compared to those found in vertebrates. In this study, we designed and used a sequence capture array to identify a novel sex-linked region (SLR) in Salix nigra, a basal species in the willow clade, and demonstrated that this species has XY heterogamety. We did not detect any genetic overlap with the previously characterized ZW SLRs in willows, which map to a different chromosome. The S. nigra SLR is characterized by strong recombination suppression across a 2 MB region and an excess of low-frequency alleles, resulting in a low Tajima's D compared to the remainder of the genome. We speculate that either a recent bottleneck in population size or factors related to positive or background selection generated this differential pattern of Tajima's D on the X and autosomes. This discovery provides insights into factors that may influence the evolution of sex chromosomes in plants and contributes to a large number of recent observations that underscore their dynamic nature.


[Intestinal parasites in inhabitants of Wrocław and Wałbrzych].
In the period 1990-1997 several thousand patients from Wrocław and Wałbrzych hospitals as well as inhabitants of Wrocław city were examined for intestinal parasites. The presence of parasites was noted in 12.3% of 2173 patients from the District Hospital of Infectious Diseases in Wrocław, 3.2% of 599 from Wałbrzych Hospital and 39.3% (mostly Enterobius vermicularis) of 746 ambulatory examined persons in the Private Analytical Laboratory in Wrocław. Among the intestinal protozoa the most frequent was Giardia intestinalis (from 5.7 to 18.1%) and Entamoeba coli (0.5-0.6%); the remaining amoebas (E. histolytica, E. hartmanni, E. polecki and Endolimax nana) as well as Chilomonas mesnili was present only in single cases. Enterobiosis was observed in nearly half of the total number of examined children (1808); the most rarely found helminths were Opisorchis felineus (! Adult patient), Strongyloides stercoralis (2) and Trichuris trichiura (8); Taenia saginata was found in 56 patients, which constituted 1.6% of the total number of examined cases and Ascaris lumbricoides in 40 (1.2%).