What is the role of adipokines in myasthenia gravis?
Myasthenia gravis (MG) is a disease with autoimmune etiology. The main pathomechanism is related to the production of antibodies against nicotinic acetylcholine receptor. The present study is aimed to compare the serum level of adipokines in patients with MG with that in controls, as well as to study the relation of these levels with disease severity. Fifty patients with MG and 30 healthy individuals were enrolled in our study. Serum concentrations of select adipokines, namely adiponectin, leptin, omentin, visfatin, and resistin were measured. The results showed a significant increase in serum concentrations of adiponectin and resistin in the patients with MG compared with the controls. Further studies are warranted to assess changes in adipokine concentration levels in patients with MG.


Understanding local electrophilicity/nucleophilicity activation through a single reactivity difference index.
A local reactivity difference index R(k) is shown to be able to predict the local electrophilic and/or nucleophilic activation within an organic molecule. Together with the electrophilic and/or nucleophilic behavior of the center k given by the sign, the magnitude of the R(k) index accounts for the extent of the electronic activation, a behavior that allows for the use of the R(k) index as a measure of the molecular reactivity especially in polar processes.


Comparison of health-related quality of life of women undergoing robotic surgery, laparoscopic surgery or laparotomy for gynecologic conditions: A cross-sectional study.
To assess and compare the health-related quality of life of women undergoing robotic gynecologic surgery, laparoscopic gynecologic surgery or laparotomy for benign and cancerous conditions. Cross-sectional study design was used. The present study was carried out with 240 women, who underwent gynecologic surgery (robotic 48, laparoscopic 96, and laparotomy 96) in a tertiary care hospital. Instruments included a participant description questionnaire and Medical Outcomes Study Short Form-36. The data were collected 4 weeks after surgery, at the first postoperative visit of women to the clinic. Pearson χ2 test, one-way analysis of variance, and regression analysis were used to assess the data. Over half of the women in each group had surgery because of gynecologic cancer. All the subscale scores of Medical Outcomes Study Short Form-36 were significantly higher in the robotic group than the other surgical groups (P < 0.05). Women in the robotic group had better quality of life in terms of both the physical component and the mental component after surgery. Knowledge of health-related quality of life in the recovery period after surgery is important for healthcare providers to provide adequate preventive measures, information, and follow up.


The Impact of Highly Effective Modulator Therapy on Cystic Fibrosis Microbiology and Inflammation.
Highly effective cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulator therapy (HEMT) corrects the underlying molecular defect causing CF disease. HEMT decreases symptom burden and improves clinical metrics and quality of life for most people with CF (PwCF) and eligible cftr mutations. Improvements in measures of pulmonary health suggest that restoration of function of defective CFTR anion channels by HEMT not only enhances airway mucociliary clearance, but also reduces chronic pulmonary infection and inflammation. This article reviews the evidence for how HEMT influences the dynamic and interdependent processes of infection and inflammation in the CF airway, and what questions remain unanswered.


Clinical Efficacy and Safety of AdV-tk Gene Therapy for Patients with Cervical Squamous Intraepithelial Lesion: A Prospective Study.
Cervical cancer is the fourth most common type of cancer for women in 2020, and many more women have cervical precancerous lesion-squamous intraepithelial lesion (SIL). Early treatment of cervical SIL to reverse or delay its progression is an important approach to reduce the incidence of cervical cancer. The efficacy and safety of adenovirus-based vectors expressing the thymidine kinase gene (AdV-tk) in the treatment of multiple types of cancers shows promise for its use in gynecology. We aim to provide relevant clinical efficacy and safety data after introducing AdV-tk for the treatment of cervical SIL for the first time through this prospective study. We conducted a maximum of 6 sessions to administer AdV-tk gene therapy to 23 patients (mean age: 35 years old) with cervical low-/high-grade SIL (LSIL/HSIL) who were enrolled from August 2015 to April 2018 and analyzed the clinical characteristics and follow-up outcomes (mean follow-up period: 7.3 months). The present study consisted of 17 patients (73.9%) with cervical HSIL and 6 patients with LSIL confirmed by colposcopy-directed biopsy. We observed an overall histological remission and regression rate of 87.0% (20/23, 95% confidence interval [95% CI]: 73.2-100, p < 0.001) after AdV-tk gene therapy. Eight patients (34.8%) were detected with human papillomavirus (HPV) 16/18 subtypes and 13 patients were found to be positive with at least one of the other 13 high-risk HPV (HR-HPV) subtypes, while 2 patients did not have any of the 15 HR-HPV subtypes. The overall clearance rate of HR-HPV was 76.2% (16/21, 95% CI: 58.0-94.4, p = 0.016) after AdV-tk gene therapy. For safety evaluation, no severe complications were reported in any of the 23 patients. The most commonly reported symptom was fever in 52.2% (12/23) of patients and all symptoms were fully resolved after symptomatic treatment. Our data indicate that AdV-tk gene therapy has high efficacy and safety in the treatment of cervical SIL among gynecological patients. Our findings provide clinical evidence on the potential promotion and application of AdV-tk in the treatment of cervical SIL, and potentially for cervical cancer, among gynecological patients.


Bleomycin stimulates both membrane (Na+-K+) ATPase and electrogenic (Na+-K+) pump and partially removes the inhibition by vanadium ions.
Bleomycin 2 X 10(-6) and 6 X 10(-6) mol.1(-1) increased the activity of specific (Na+-K+) ATPase of the rat brain microsomes. It also stimulated the electrogenic (Na+-K+) pump in intact skeletal muscle cells. The blocking effect of vanadyl (+4V) on membrane (Na+-K+) ATPase was eliminated completely by the drug, but the action of vanadate (+5V) was counteracted only partially. Electron paramagnetic resonance spectra revealed the formation of a +4V - bleomycin complex which is still able to activate the (Na+-K+) ATPase.


Small interfering RNAs generated by recombinant dicer induce inflammatory gene expression independent from the TAK1-NFkappaB-MAPK signaling pathways.
Generation of mixtures of small interfering (si) RNAs by recombinant dicer avoids selection of efficient target sites within mRNAs but little is known about off-target effects of this approach. Using recombinant human dicer we generated siRNA mixtures (dsiRNA) directed against the protein kinase TAK1 and its subunit TAB1, important upstream molecules in the pathways activated by IL-1, TNF, and toll-like receptors (TLR). dsiRNA against TAK1 or TAB1 significantly suppressed their target proteins as well as TAK1-mediated activation of NFkappaB, p38 MAPK, and JNK, and of IL-8 transcription. However, microarray analysis of 136 endogenous inflammatory genes revealed that dsiRNA against TAB1 or TAK1 did not suppress IL-1 or TNF-induced genes but rather induced a broader range of 15 inflammatory genes as well as seven known interferon-response genes. The same genes were induced by dsiRNA directed against luciferase but not by a synthetic control siRNA molecule. Hence, our results show that complex mixtures of siRNA induce an inflammatory gene response that is independent from TAK1-mediated signal transduction. In the light of the increasing usage of enzymatically prepared libraries of siRNA these results provide important insight into potential off-target effects of this approach.


The intraoperative motor-evoked potential when propofol was changed to remimazolam during general anesthesia: a case series.
Remimazolam is a short-acting benzodiazepine that was approved for clinical use in 2020. We report three patients who underwent surgery for cerebral and spinal cord tumors, in whom transcranial electrical stimulation-motor-evoked potential (TES-MEP) was successfully monitored under general anesthesia with remimazolam. During total intravenous anesthesia with propofol at a target concentration of 2.7 - 3.5 µg/mL and 0.1 - 0.35 µg/kg/min of remifentanil, delayed awakening, bradycardia, and hypotension during propofol anesthesia were expected in all three cases. With patient safety as the top priority, we considered changing the anesthetic agent. Propofol was replaced with remimazolam at a loading dose of 12 mg/kg/h for a few seconds (case 3), followed by 1 mg/kg/h for maintenance (cases 1-3). TES-MEP was recorded during propofol and remimazolam administration in all three patients. Amplitudes of TES-MEP during anesthesia with propofol and remimazolam were 461.5 ± 150 µV and 590.5 ± 100.9 µV, 1542 ± 127 µV and 1698 ± 211 µV, and 581.5 ± 91.3 µV and 634 ± 82.7 µV sequentially from Case 1. Our findings suggest that intraoperative TES-MEP could be measured when anesthesia was managed with remimazolam at 1 mg/kg/h.


Compensatory responses of goat mothers to their impaired young.
The behaviour of a mother goat towards her young normally compensates for differences between them in their vigour at birth. Weakening the first-born with drugs still does not prevent its getting equal access to the udder, though weakening the second-born may render it so much less vigorous that maternal compensation does fail. When the mother is unable to distinguish her kids by sight or smell, she is unable to modulate her responses to the kids and then the more vigorous kid always establishes priority of access to the bladder. We conjecture that this is what normally occurs under harsh environmental conditions where the mother's milk supply is occasionally inadequate for two kids.


Reflections on the origins of meta-analysis.
In this interview, we discuss my early uses of meta-analytic procedures, first to combine p-values and then to combine effect sizes as well. My interest in quantifying the magnitude and the statistical significance of the effect of interpersonal expectations probably grew out of the following: (1) a long-held interest in the concept of replication and (2) a series of controversies over the very existence of any effect of interpersonal expectations held, for example, by psychological experimenters, classroom teachers, and leaders of various organizations.


The costs of parental pressure to express emotions: conditional regard and autonomy support as predictors of emotion regulation and intimacy.
This research focuses on offspring's perceptions of their parents' usage of conditional regard and autonomy-supportive practices in response to the offspring's experiences of negative emotion. Participants were 174 college students (60% were females). As predicted from self-determination theory (Ryan & Deci, 2000), students' perceptions of parents as hinging their regard on students' expression or suppression of negative emotions predicted a maladaptive pattern of emotion regulation and intimacy capacity. In contrast, autonomy-supportive parenting predicted more adaptive emotion regulation and intimacy patterns. Also as predicted, emotion-regulation mode mediated the relations between parental practices and intimacy capacity. The innovative aspect of the study is the finding that parents who use conditional regard to encourage children's expression (sharing) of negative emotions may actually undermine their children's socioemotional capacities.


Age-related changes of circadian rhythms and sleep-wake cycles.
To compare relationships between the sleep-wake cycle and endogenous circadian rhythms in young and older adults and to examine correlates between evening naps and circadian rhythms in older adults. For 1 week of home recording, subjects wore wrist-activity monitors and kept daily sleep logs. After the home monitoring, subjects entered the laboratory on a 90-minute sleep-wake schedule and were monitored on this schedule for at least 30 hours. Community living and laboratory. Sixty-seven young adults, aged 18 to 32, and 56 older adults, aged 60 to 75, who were healthy and had few sleep complaints. Times of nocturnal sleep, out-of-bed napping, and illumination were obtained at home. Sleep propensity and oral body temperature (OBT) were measured in the laboratory, along with circadian rhythms of cortisol and 6-sulfatoxymelatonin (aMT6s, assayed from urine samples collected every 90 minutes). Home sleep times and illumination acrophases (fitted peak times) were advanced in older adults. The phase angles (time intervals) between onset of aMT6s and sleep onset were not changed in older adults, but sleep offset was more advanced than acrophase and offset of aMT6s with aging. Acrophases of cortisol and sleep propensity were advanced in older adults to the same extent as sleep times, but OBT was less advanced than sleep times. Older adults who took evening naps showed more advanced sleep offset and circadian rhythms of aMT6s, but there were no differences in the phase angles of sleep onset and circadian rhythms of aMT6s and cortisol compared with older adults who did not take evening naps. Measuring different circadian markers suggested different phase relationships between the sleep-wake cycle and endogenous circadian rhythms in aging. Early awakening in older adults cannot be explained simply by a relative phase advance of the circadian system. Evening naps and advanced illumination may play a role in the advance of the circadian system in aging.


Acute percheron infarction: a precision learning.
So far, the diagnosis of acute artery of percheron (AOP) infarction is uncommon. In this study, patients with acute AOP infarction were studied to explore the relationship of imaging findings, clinical manifestations and prognosis of acute AOP infarction. A total of 23 patients with acute AOP infarction in our institution from 2014 to 2019 were reviewed retrospectively. All cases were evaluated by computed tomography (CT) and magnetic resonance imaging (MRI). The modified Rankin scale (MRS), blood examination, electrocardiogram and transthoracic echocardiography were used for detailed clinical and prognostic evaluation. All standard risk factors for these patients were recorded. The MRS scores were performed 90 days after discharge. Four different types of acute AOP infarction were identified: (a) bilateral paramedian thalamic infarction (BPTI, 52%); (b) bilateral paramedian thalamic with rostral midbrain infarction (BPTRMI, 30%), (c) bilateral paramedian and anterior thalamic infarction (BPATI, 13%), and (d) bilateral paramedian thalamic with red nuclei infarction (BPTRNI, 4%). These patients had consciousness disorder, memory dysfunctions, vertical gaze paresis and mesencephalothalamic syndrome. The 65% of patients with BPTI and BPATI experienced relatively good functional recovery and could carry out daily life activities (MRS score ≤ 2). However, patients with BPTRMI may have an unfavorable outcome. Although the clinical features are variable, DWI or ADC map can improve the diagnosis of acute AOP infarction patterns. Acute AOP occlusion requires immediate diagnosis and treatment to obtain more favorable outcome and avoid additional unnecessary procedures.


Life events, fitness, hardiness, and health: a simultaneous analysis of proposed stress-resistance effects.
The effects of exercise participation, self-perceived fitness level, and dispositional hardiness for promoting stress resistance were examined in a sample of 373 college students. Self-report measures of stressful life experience and recent physical illness were positively correlated, and fitness and hardiness were negatively correlated with illness as expected. Multiple regression analyses indicated that neither fitness nor hardiness provided a stress-moderator effect because neither was found to significantly interact with stress in the prediction of illness scores. Structural equation analyses suggested that hardiness may affect health indirectly by first influencing either the occurrence or subjective interpretation of stressful life events. No direct effect on health was found for exercise participation, although exercise may reduce illness indirectly by improving fitness. Implications for the multivariate modeling of proposed stress-resistance-enhancing effects are discussed.


Machine Learning and Non-Affective Psychosis: Identification, Differential Diagnosis, and Treatment.
This review will cover the most relevant findings on the use of machine learning (ML) techniques in the field of non-affective psychosis, by summarizing the studies published in the last three years focusing on illness detection and treatment. Multiple ML tools that include mostly supervised approaches such as support vector machine, gradient boosting, and random forest showed promising results by applying these algorithms to various sources of data: socio-demographic information, EEG, language, digital content, blood biomarkers, neuroimaging, and electronic health records. However, the overall performance, in the binary classification case, varied from 0.49, which is to be considered very low (i.e., noise), to over 0.90. These results are fully justified by different factors, some of which may be attributable to the preprocessing of the data, the wide variety of the data, and the a-priori setting of hyperparameters. One of the main limitations of the field is the lack of stratification of results based on biological sex, given that psychosis presents differently in men and women; hence, the necessity to tailor identification tools and data analytic strategies. Timely identification and appropriate treatment are key factors in reducing the consequences of psychotic disorders. In recent years, the emergence of new analytical tools based on artificial intelligence such as supervised ML approaches showed promises as a potential breakthrough in this field. However, ML applications in everyday practice are still in its infancy.


Preimplantation genetic diagnosis of single-gene disorders: experience with more than 200 cycles conducted by a reference laboratory in the United States.
To evaluate trends and outcomes from preimplantation genetic diagnosis (PGD) cycles. Retrospective data review. A reference laboratory specializing in the provision of PGD services. One hundred sixty-two patients at risk of transmitting a serious monogenic disorder to their children. In vitro fertilization and PGD. Results of PGD cycles. Two hundred twenty-four PGD cycles were referred by 59 different IVF centers. Forty-six different disorders were diagnosed, including several not previously diagnosed at the preimplantation stage. Cystic fibrosis was the most common reason for referral (73 cases). A diagnosis was obtained for 84.4% of tested embryos, with results available 6 to 36 hours from sample receipt. Only 10.7% of cycles had no transfer. The pregnancy rate per cycle with ET was 43.4%. Unlike previous reports of multiple PGD cycles, all of the cases in this study involved shipping of biopsied cells to a specialist reference laboratory for diagnosis. This approach, sometimes referred to as "transport PGD," accounts for the vast majority of PGD cycles in the United States. Preimplantation genetic diagnosis was shown to be an effective alternative to prenatal diagnosis for patients with an ethical or a religious objection to pregnancy termination and for infertile patients carrying a genetic disorder. Demand for this service at our center doubled in each of the last 4 years. Pregnancy rates per ET were encouraging, almost half of all patients undergoing their first PGD cycle achieving a birth or ongoing pregnancy.


Treatment and Outcomes of Tusk Fractures in Managed African Savanna and Asian Elephants (Loxodonta africana and Elephas maximus) across Five Continents.
Elephant tusk fractures are a clinical challenge that can impact the overall health of the animal, particularly when they result in pulp exposure. An international survey was sent to veterinarians to understand individual fracture characteristics and management strategies as they relate to outcomes, with the goal of better informing treatment procedures. The data set consisted of 79 fractures from 64 elephants (including Asian and African males and females), 44.3% of which were Class III fractures with pulpal involvement. Of this subset, pulp canal exposures of >0.5 cm were 23.8-fold more likely to develop pulpitis than fractures with <0.5 cm exposed, though canal size did not impact healing versus extraction outcome. Odds ratios showed that treatments including endodontics were 12.0-fold more likely to heal than tusks treated exclusively with medical management, though no association was observed in reducing the risk of pulpitis. Further, pulpitis was 7.58-fold more likely to develop when tap water was used to rinse exposed pulpal tissue; a finding that merits further investigation. The use of endodontic treatment versus medical management alone was significantly associated with improved recovery outcomes (i.e., reduced risk of extraction) in tusk fractures with pulpal involvement.


Comparison of biomechanical properties of bile duct between pigs and humans for liver xenotransplant.
Pigs have been regarded as the preferred source of organs for human xenotransplantation. The aim of the present study was to explore the biomechanical properties of the bile duct in pigs and humans to provide evidence for liver xenotransplantation. Fresh bile duct specimens obtained from 50 pigs aged 3 to 12 months and five deceased human donors. The diameters and wall thickness of the bile duct were measured using a computer imaging analysis system. The pressure-diameter of bile ducts was tested with biomechanical equipment. The corresponding parameters were calculated: incremental elastic moduli (E(inc)), pressure-strain elastic modulus (E(p)), volume elastic modulus (E(v)), and compliance. The E(inc), E(p), and E(v) of porcine bile duct gradually decreases with age. However, the E(inc), E(p), and E(v) gradually increased after pigs aged 10 months. The E(inc), E(p), and E(v) of pig bile ducts aged 3 to 6, and 11 to 12 months were higher than that of humans aged 20 to 40 years (P < .01). The changes in compliance of the porcine bile duct with age oppose those in elastic modulus. There were no significant differences in the elastic modulus and compliance of the bile duct between pigs aged 7 to 10 months and adult humans (P > .05). The biomechanical properties of the bile duct of pigs aged 7 to 10 months match that of adult humans. The correlation between age and biomechanical properties of bile ducts in pigs implied that a pig aged 7 to 10 months should be chosen for pig-to-human liver xenotransplantation.


Exogenous infusion of short-chain fatty acids can improve intestinal functions independently of the gut microbiota.
The present experiment was conducted to investigate the effects of exogenously infused short-chain fatty acids (SCFAs) on the growth development and intestinal functions in a germ-free (GF) pig model. Twelve hysterectomy-derived newborn piglets were reared in six sterile isolators. All piglets were hand-fed Co60-γ-irradiated sterile milk powder for 21 d and then were switched to sterile feed for another 21 d. During the second 21-d period, GF piglets (n = 6) were orally infused with 25 mL/kg sterile saline per day, and SCFA piglets (n = 6) were orally infused with 25 mL/kg SCFAs mixture (acetic, propionic, and butyric acids, 45, 15, and 11 mM, respectively) per day. We observed the concentrations of SCFAs in serum and intestine, and the messenger ribonucleic acid (mRNA) abundance of G-protein-coupled receptor-43 in the ileum was increased (P < 0.05) in the SCFA group. Meanwhile, oral infusion of SCFAs enhanced (P < 0.05) the contents of glucagon-like peptide-2 in the jejunum and serum and tended to increase the villi height in the ileum (P < 0.10). Besides, the activities of lipase, trypsin, sucrase, lactase, Na+-K+-adenosine triphosphatase ([ATPase] P < 0.05), and Ca2+-Mg2+-ATPase (P < 0.10) were stimulated and the mRNA expressions of solute carrier family 7 (SLC7A1) and regeneration protein (REG)-ΙΙΙ γ in the jejunum (P < 0.05) were upregulated in the SCFA group. Additionally, SCFAs infusion downregulated the mRNA abundances of interleukin (IL)-1β and IL-6 in the jejunum, ileum, or colon (P < 0.05) and increased the counts of white blood cell, neutrophils, and lymphocyte in the blood (P < 0.05). Collectively, exogenous infusion of SCFAs might improve intestinal health through promoting intestinal development and absorption function, and enhancing intestinal immune function, and these effects were occur independently of the gut microbiota.


Side-effects of a systemic injection of linear polyethylenimine-DNA complexes.
Systemic administration of linear polyethylenimine-DNA complexes (L-PEI/DNA) results in transient expression of the transgene in the lung. This study analyzes the side-effects associated with L-PEI-mediated transfection. Mice weighing from 16 to 25 g received increasing amounts of L-PEI/DNA intravenously. Gene expression was evaluated using luciferase as a reporter gene. Toxicity was evaluated by monitoring the appearance of shock after injection, the survival of the animals, and the microscopic damage in the tissues. Adherence of blood cells and endothelium activation were observed after CD11-b and von Willebrand immunostaining. Anti-aggregant treatments were used in order to prevent the formation of thrombi. Increasing the quantity of L-PEI/DNA resulted in a marked augmentation of the luciferase activity in the lung, but was associated with liver necrosis and death. Lethality was reached at lower doses in older mice, suggesting an age influence. Transfection was associated with activation of the lung endothelium and increased adhesion of small aggregates containing platelets and CD11-b-positive cells, without the appearance of large thrombi and of lung injury. Anti-aggregant treatments (aspirin, EDTA, heparin or clopidogrel) decreased the L-PEI-mediated transfection, supporting the hypothesis that platelets participate in the blocking of DNA complexes in the lung capillaries. This study demonstrates that L-PEI/DNA activates the lung endothelium and forms small aggregates, a side-effect linked to the transfection efficiency.


Acute-phase changes in children recovering from minor surgery.
The metabolic response to surgical stress is a nonspecific increase in hepatic synthesis of some specialized acute-phase proteins and a decrease in plasma concentrations of visceral proteins following surgical trauma. This study was undertaken determine which specific proteins were the better clinical indices in monitoring the metabolic response to surgical stress in children recovering from minor surgery. Forty-four patients undergoing elective inguinal surgical procedures under general anesthesia were studied. Blood samples were collected preoperatively (-1) and at 1(+1) and 5(+5) days postoperatively to determine albumin (AL), Prealbumin (PA), C-reactive protein (CRP), and a1-acid glycoprotein (AGP) values, and to calculate the prognostic inflammatory and nutritional index (PINI). Mean AL values were the same on all days. Mean PA +1 was significantly lower than PA -1 and PA +5 (P < 0.001). Median CRP +1 and mean AGP +1 values were significantly higher than median CRP -1 and mean AGP -1 (P < 0.0001), respectively. Although there was a decrease after postoperative day 1, median CRP +5 and mean AGP +5 values were still significantly higher than preoperative values (P < 0.01 and P < 0.0001). Moreover, the median PINI +1 was also greater than PINI -1 and PINI +5 (P < 0.0001), but the median PINI+5 was significantly higher than PINI -1 (P < 0.01). Median percent changes of PINI values were significantly higher than those of the other parameters from both preoperatively to postoperative day 1 and preoperatively to postoperative day 5. Although several specific proteins (AL, PA, CRP, and AGP) have been evaluated as indicators of the acute metabolic response, we suggest that the PINI is more valuable for reflecting the response to surgical stress in patients recovering from minor surgery.


Targeted deletion of Crif1 in mouse epidermis impairs skin homeostasis and hair morphogenesis.
The epidermis, which consists mainly of keratinocytes, acts as a physical barrier to infections by regulating keratinocyte proliferation and differentiation. Hair follicles undergo continuous cycling to produce new one. Therefore, optimum supply of energy from the mitochondria is essential for maintaining skin homeostasis and hair growth. CRIF1 is a mitochondrial protein that regulates mitoribosome-mediated synthesis and insertion of mitochondrial oxidative phosphorylation polypeptides into the mitochondrial membrane in mammals. Recent studies reveal that conditional knockout (cKO) of Crif1 in specific tissues of mice induced mitochondrial dysfunction. To determine whether the mitochondrial function of keratinocytes affects skin homeostasis and hair morphogenesis, we generated epidermis-specific Crif1 cKO mice. Deletion of Crif1 in epidermis resulted in impaired mitochondrial function and Crif1 cKO mice died within a week. Keratinocyte proliferation and differentiation were markedly inhibited in Crif1 cKO mice. Furthermore, hair follicle morphogenesis of Crif1 cKO mice was disrupted by down-regulation of Wnt/β-catenin signaling. These results demonstrate that mitochondrial function in keratinocytes is essential for maintaining epidermal homeostasis and hair follicle morphogenesis.


Relation between indices of semen analysis and pregnancy rate in infertile couples.
Both partners of 198 consecutive infertile couples were evaluated. Studies in the female included clinical evaluation of ovulation for a minimum of two menstrual cycles, investigation of tubal patency, and evaluation of sperm survival in cervical mucus. Six semen specimens were analyzed from each male. Laparoscopy, scrotal exploration, and testicular biopsies were performed as required. Where indicated, the female was treated intensively. The only therapy offered to the males was ligation of varicoceles, if present. The couples were grouped on the basis of sperm counts, total sperm counts, motile sperm counts, and total motile sperm counts, and the incidence of pregnancy was computed. Pregnancy rates of approximately 50% occurred in couples where sperm counts or total sperm counts were in the range of 5 to 60 million/ml or 25 to 200 million/ejaculate, respectively. When sperm counts were over 60 million/ml or total sperm counts over 200 million/ejaculate, pregnancy rates increased to above 70%. These observations emphasize the importance of considering infertility as a problem of a couple rather than as a specific disorder of one of the partners. These data also demonstrate a lack of direct correlation between sperm density in the ranges of 5 to 60 million/ml and pregnancy rates in couples where the wife is treated intensively.


Radiotherapy in the management of early breast cancer: a review.
Breast conserving therapy with adequate radiotherapy results in similar local control and survival in patients with early breast cancer. Radiotherapy has proven to be an integral part of this treatment as in the NSABP trial a significant reduction of breast recurrences occurred after irradiation, compared with tumorectomy alone. The entry criteria of the performed randomized trials were initially limited to patients with tumours up to 2 cm diameter, but even patients with incompletely excised tumours up to 5 cm have been accepted in the recently closed EORTC trial 10801. This means that this conservative approach is now accessible for a much larger group of patients with breast cancer. A few factors related to a somewhat higher recurrence rate in the breast are: extensive ductal carcinoma in situ, younger age and incomplete excision. These factors are, however, not absolute contra-indications for breast conserving therapy because wide reexcision of the primary tumour or a high booster dose are likely to correct for these unfavourable factors. Future clinical research is required to optimize the irradiation with reduction of side-effects and maintaining a high local control rate.


Chain propagation determines the chemo- and regioselectivity of alkyl radical additions to C-O vs. C-C double bonds.
Investigations into the selectivity of intermolecular alkyl radical additions to C-O- vs. C-C-double bonds in α,β-unsaturated carbonyl compounds are described. Therefore, a photoredox-initiated radical chain reaction is explored, where the activation of the carbonyl-group through an in situ generated Lewis acid - originating from the substrate - enables the formation of either C-O or the C-C-addition products. α,β-Unsaturated aldehydes form selectively 1,2-, while esters and ketones form the corresponding 1,4-addition products exclusively. Computational studies lead to reason that this chemo- and regioselectivity is determined by the consecutive step, i.e. an electron transfer, after reversible radical addition, which eventually propagates the radical chain.


Molecular imaging of macrophage enzyme activity in cardiac inflammation.
Molecular imaging is highly advantageous as various insidious inflammatory events can be imaged in a serial and quantitative fashion. Combined with the conventional imaging modalities like computed tomography (CT), magnetic resonance (MR) and nuclear imaging, it helps us resolve the extent of ongoing pathology, quantify inflammation and predict outcome. Macrophages are increasingly gaining importance as an imaging biomarker in inflammatory cardiovascular diseases. Macrophages, recruited to the site of injury, internalize necrotic or foreign material. Along with phagocytosis, activated macrophages release proteolytic enzymes like matrix metalloproteinases (MMPs) and cathepsins into the extracellular environment. Pro-inflammatory monocytes and macrophages also induce tissue oxidative damage through the inflammatory enzyme myeloperoxidase (MPO). In this review we will highlight recent advances in molecular macrophage imaging. Particular stress will be given to macrophage functional and enzymatic activity imaging which targets phagocytosis, proteolysis and myeloperoxidase activity imaging.


Initial experience with the Cosgrove-Edwards Annuloplasty System.
The mitral valve has a nonplanar shape and a sphincter action. Pathologic dilatation occurs along the posterior annulus. To preserve the physiologic function and correct annular dilatation, we developed an annuloplasty system that is universally flexible and produces a measured plication of the posterior annulus (Cosgrove-Edwards Annuloplasty System). The results of 150 consecutive mitral valve repairs using this system were analyzed. Mean age was 58 +/- 13 years; 59% were men. The cause of the valve disease was degenerative in 75% of the patients, rheumatic in 13%, ischemic in 8%, and infectious in 4%. Associated procedures were performed in 61 patients (41%). Echocardiographic mitral regurgitation decreased from 3.7 +/- 0.6 before repair to 0.2 +/- 0.4 after repair (p < 0.0001). There were no hospital deaths and no cases of hemodynamically significant systolic anterior motion or other annuloplasty-related complications. Follow-up was 100% complete at a mean of 3.1 +/- 3.6 months. There were three late deaths, three transient ischemic attacks, and one episode of endocarditis. Five patients (3.3%) have undergone reoperation for recurrent mitral insufficiency; no reoperations were related to the annuloplasty system. At a mean of 9 months, three-dimensional reconstruction of the mitral annulus from multiple echocardiographic images confirmed the nonplanar shape and sphincter mechanism of the annulus. Annular orifice area decreased 19% during the cardiac cycle from a mean of 10.3 cm2 in diastole to 8.6 cm2 in systole. This annuloplasty system is effective for repair of insufficiency secondary to all causes, preserves physiologic annulus function, and is associated with a low incidence of valve-related complication.


Optimal strategy of coronary revascularization in chronic kidney disease patients: a meta-analysis.
Patients with chronic kidney disease (CKD) have high risks of coronary artery disease (CAD). Coronary revascularization is beneficial for long-term survival, but the optimal strategy remains still controversial. We searched studies that have compared percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) for revascularization of the coronary arteries in CKD patients. Short-term (30 days or in-hospital) mortality, long-term (at least 12 months) all-cause mortality, cardiac mortality and the incidence of late myocardial infarction and recurrence of revascularization were estimated. 28 studies with 38,740 patients were included. All were retrospective studies from 1977 to 2012. Meta-analysis showed that PCI group had lower short-term mortality (OR 0.55, 95% CI 0.41 to 0.73, P<0.01), but had higher long-term all-cause mortality (OR 1.29, 95% CI 1.23 to 1.35, P<0.01). Higher cardiac mortality (OR 1.08, 95% CI 1.01 to 1.15, P<0.05), higher incidence of late myocardial infarction (OR 1.78, 95% CI 1.65 to 1.91, P<0.01) and recurring revascularization rate (OR 2.94, 95%CI 2.15 to 4.01, P<0.01) is found amongst PCI treated patients compared to CABG group. CKD patients with CAD received CABG had higher risk of short-term mortality but lower risks of long-term all-cause mortality, cardiac mortality and late myocardial infarction compared to PCI. This could be due to less probable repeated revascularization.


The impact of genetic engineering on the commercial production of antibiotics by Streptomyces and related bacteria.
Developments in Streptomyces genetics that have laid a foundation for this field over the past ten years are reviewed and discussed to suggest how this knowledge might useful for improving the commercial production of antibiotics. This brief analysis predicts a bright future for the application of Streptomyces genetics in antibiotic production.


Double JJ Ureteral Stenting: Encrustation and Tolerability.
Indications for stenting should be considered and the stent indwelling time should be minimised. Silicone stents are superior in terms of lower rates of encrustation and stent symptoms. α-Blockers may have an off-label role in reducing both pain and urinary symptoms, while keeping an up-to-date stent register may help in ensuring that stents are not forgotten.


Cyclic AMP-dependent and -independent effects of beta-adrenergic stimulation on the contraction-relaxation cycle of spontaneously beating rat atria.
The effects of isoproterenol (ISO, 1 X 10(-7) M) and phenylephrine (beta-PHEN, 5 X 10(-5) M, in the presence of 5 X 10(-6) M phentolamine) as well as the effect of hypercalcemia (5.7 X 10(-3) M instead of 1.9 X 10(-3) M) on the kinetics of changes in developed tension (DT) and its second derivative (T") and on cAMP level and 45Ca uptake were studied in spontaneously beating rat atria. Both the effects of ISO and the beta-adrenergic effect of PHEN on amplitude were equipotent 15 and 60 sec after administration. However, the ISO response developed faster, and the amplitude at 30 sec was significantly higher in the ISO than in the PHEN response. The effects of ISO on the ratio of the amplitudes of the first maximum and the minimum of T" (T"max/T"min) as well as on the duration of the contraction-relaxation cycle (CRC) were biphasic. At 15 sec, it first produced increases, and subsequently, 60 sec after the drug, these parameters decreased below the control. beta-Phenylephrine produced a similar biphasic response in the ratio T"max/T"min, but the duration of CRC appeared only to decrease 60 sec after the drug. The durations of the contraction phases of T" were reduced both by ISO (30 and 60 sec) and beta-PHEN (60 sec) after administration. All of the effects of beta-PHEN on T" were weaker than those induced by ISO. Furthermore, the ability of PHEN to stimulate the formation of cAMP was also poorer. The inhibition of phosphodiesterase by methylisobutylxanthine enhanced, dose dependently, the increase in the relaxing components of CRC. However, the amplitude response of ISO was antagonized by this drug. The time course effects of ISO on the amplitude and cAMP were parallel. beta-Phenylephrine stimulated first contractility and much later an increase in cAMP. Uptake of 45Ca was stimulated equally by ISO and beta-PHEN. Hypercalcemia produced increases in amplitude, in the ratio T"max/T"min, and in the duration of CRC but no change in the level of cAMP. The data suggest that the beta-adrenergic response is at the outset qualitatively similar to the response of hypercalcemia and that the typical changes in CRC for beta stimulation take place only secondly. Thus, even though cAMP is involved in beta-adrenergic stimulation, it may not be the main cause of positive inotropism. The qualitative changes in CRC, i.e., the increase in the relaxing components and the decrease in time to peak tension, could be responsible for the faster increase in amplitude to the steady-state level.


Comparison of cytologic preparation methods in endoscopic ultrasound-guided fine needle aspiration for diagnosis of pancreatic adenocarcinoma.
There are few studies about the diagnostic yield of cytologic preparation method of pancreatic samples obtained by Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). The aim of this study was to compare the accuracy of ThinPrep(®) and smear method in diagnosis of pancreatic cancer. A total of 125 EUS-FNA procedures were performed between July 2010 and June 2015. Patients in group I (n = 36; July 2010 to June 2014) had cytology slides prepared by consecutive allocation of samples. Patients in group II (n = 12; July 2014 to June 2015) had cytology slides prepared by alternately allocation of samples. There were 24 men and 24 women (median age: 67 years; range 39-84). The median size of lesions was 3.9 cm (range; 1.4-7.2 cm). The locations of the pancreatic cancer were 10 in head (20.8%), 21 in body (43.8%), and 17 in tail (35.4%). The ThinPrep(®) method confirmed malignancy in 35 of 48 cases (72.9%). On the other hand, the smear method confirmed malignancy in 44 of 48 cases (91.7%). The diagnostic yield of smear method was statistically higher than liquid method (P = 0.012). Also, smear method is superior to liquid method in both consecutive and alternative allocation method. ThinPrep(®) provided a correct diagnosis in one case where the smear method was incorrect. Smear method was a superior preparation method to liquid method in diagnosis of pancreatic cancer, even if splitting method was not used and variable allocation method was used.


Biopharmaceutical characteristics of a suppository base containing poly (oxyethylene)-poly (oxypropylene) copolymer, Unilube. I. Effects of a suppository base containing Unilube 70DP-950B on release and rectal absorption of aminopyrine in rabbit.
The rectal absorption of aminopyrine (AP) from a three-component-system suppository base (TCS), which is a mixture of oleaginous base, water-soluble base and the poly-(oxyethylene) poly-(oxypropylene) block copolymer, Unilube, was investigated. Albino rabbits were used as the animal model. The bioavailability of oleaginous base and water-soluble base (polyethylene glycol 4000) were 44.3% and 82.6%, respectively. The time to reach maximum plasma concentration (Tmax) of the oleaginous and the water-soluble bases were 21.0 +/- 8.2 min and 33.0 +/- 16.4 min, respectively. When TCS was used, its Tmax was 30 min and increasing the amount of Unilube in the base from 5% (w/w) to 20% (w/w) decreased the bioavailability from 100.4% to 47.2%. The softening temperature of TCS was 55-57 degrees C. Collectively, TCS containing 5% of Unilube gave significantly higher bioavailability than the other bases without softening until 57 degrees C. Also, the results of the two different release tests were compared with the results of an animal experiment in this paper.


Development and external validation of a dynamic nomogram for delayed cerebral ischaemia after aneurysmal subarachnoid hemorrhage: a study protocol for a multicentre retrospective cohort study.
Delayed cerebral ischaemia (DCI) caused by aneurysmal subarachnoid haemorrhage (aSAH) is the most frequent complication and typically contributes to poor neurological outcome or deterioration of patients' condition. Therefore, early accurate and effective prediction of DCI is urgently needed. This study aims to construct a dynamic nomogram for precisely calculating the risk of DCI in patients with aSAH. Internal validation of this tool is conducted using the training cohort, and independent external validation is completed by using other medical centre datasets. This study is a multicentre, retrospective, observational cohort study using data from patients with aSAH. The participants include all adult patients who received surgical treatment in neurosurgery of multiple medical centres from 1 September 2019 to 1 April 2021, including Renmin Hospital of Wuhan University, Huzhou Central Hospital, First Affiliated Hospital of Harbin Medical University, General Hospital of Northern Theatre Command and Affiliated Hospital of Panzhihua University. Clinical information is collected via the electronic medical record system, including demographic data, clinical state on admission and serum laboratory tests. Modified Fisher grade at admission, admission subarachnoid clot and cerebral oedema density, and residual postoperative subarachnoid clot density are determined using the electronic imagine record software. The primary outcome is DCI. This study protocol was reviewed and approved by the Medical Ethics Committee of Renmin Hospital of Wuhan University, which is the principal affiliation of this study (approval number: WDRM2021-K022). The other Ethics Committees, including Huzhou Central Hospital (approval number: 202108005-01), First Affiliated Hospital of Harbin Medical University (approval number: H202156), General Hospital of Northern Theater Command (approval number: Y2021060) and Affiliated Hospital of Panzhihua University (approval number: 202105002), also approved the protocol. The results of this research will be published in a peer-reviewed medical journal. ChiCTR2100044448.


Pupillary dynamics predict long-term outcome in a cohort of acute traumatic brain injury coma patients.
Examining the size and reactivity of the pupils of traumatic brain injury coma patients is fundamental in the Neuro-intensive care unit (ICU). Pupil parameters on admission predict long-term clinical outcomes. However, little is known about the dynamics of pupillary parameters and their potential value for outcome prediction. This study applied a time-course analysis of pupillary signals (size and photo-reactivity) in acute traumatic brain injury coma patients (n = 20) to predict outcome at 6 months. The time course of pupillary signals was informative in discriminating favorable (F) versus unfavorable (U) outcomes, with the highest correlation within the 1st week notwithstanding pharmacological sedation. Patients with favorable outcome at 6 months showed more consistent in time isochoric and photo-reactive pupils. In contrast, patients with an unfavorable outcome showed more variable measures that tended to stabilize toward pathological values. Time-dependent tracking of pupils' size and reactivity is a promising application for ICU monitoring and long-term prognosis. These findings support the usefulness of automatic tools for the dynamic, quantitative, and objective measurements of pupils.


β-Cyclodextrin anchoring onto pericarpium granati-derived magnetic mesoporous carbon for selective capture of lopid in human serum and pharmaceutical wastewater samples.
Functionalized magnetic carbonaceous nanomaterials, which are important materials with many practical and research applications in biomedical, pharmaceutical and biological fields, have recently attracted much attention. In this study, a magnetic mesoporous carbon coated with β-cyclodextrin (MMC@β-CD) was synthesized for the first time from natural pericarpium granati (PG). The as-obtained MMC@β-CD has high surface areas (203 m(2)g(-1)), large pore volumes (0.16 cm(3)g(-1)), relatively broad mesoporous sizes (6.8 nm) and a high saturation magnetization of 26.2 emu g(-1), which is sufficient for magnetic separation by an external magnetic field. The MMC@β-CD was used as an innovative adsorbent for magnetic solid-phase extraction of lopid via host-guest interaction prior to spectrofluorometric analysis. The proposed method was successfully applied to analyze lopid in human serum and pharmaceutical wastewater samples with recoveries in the range of 85.0-103.5% for the spiked samples. Overall, this work not only provides an inexpensive and eco-friendly method to fabricate MMC@β-CD (or MMC) from PG, but also develops a highly selective approach for capture of lopid in biological samples and environmental substances.


Managed Care after Acute Myocardial Infarction (MC-AMI) - Poland's nationwide program of comprehensive post-MI care improves prognosis in 2-year follow-up. A single high-volume center intention-to-treat analysis.
Managed Care in Acute Myocardial Infarction (MC-AMI) is a program introduced in Poland aimed at comprehensive, scheduled, and supervised care for AMI patients to improve longterm prognosis. Our study aimed to compare 24-month mortality and the incidence of major cardiovascular events (MACE: a composite of death, recurrent MI, and hospitalization for heart failure) in a cohort of AMI patients treated in the MC-AMI era (intention-to-treat analysis) vs. similar population treated before the MC-AMI era. We analyzed 2323 consecutive patients with AMI: 1261 patients enrolled in the MC-AMI era (study group) and 1062 patients treated 12 months before the MC-AMI era (control group). In the study group, 57% of patients participated in MC-AMI while 43% of patients remained under standard care. The patients were followed up for 24 months. Mortality and MACE were recorded. Treatment in the MC-AMI era was related to a 30% reduction in all-cause mortality and a 14% reduction of MACE although it was not related to the reduction of hospitalization for heart failure (HF) or AMI in 24 months. The 24-month survival rate was the highest in MC-AMI enrolled patients while patients treated in the MC-AMI era but not enrolled had a similar prognosis to those treated before the MC-AMI era. Multivariable Cox regression analysis revealed the MC-AMI era to be inversely associated with mortality in 24-month follow-up (hazard ratio [HR], 0.49; 95% confidence interval [Cl], 0.38-0.65; P <0.001). AMI treatment in the MC-AMI era reduces 24-month mortality and MACE. Moreover, AMI treatment in MC-AMI is inversely related to mortality, MACE, and hospitalization for HF. The effect is pronounced in patients enrolled in MC-AMI.


Characterization of pertussis toxin by LC-MS/MS.
Liquid chromatography-mass spectrometry (LC-MS) with a dual spray electrospray ionization source has been used to measure the molecular weights of pertussis toxin (PT) subunits. Measurement accuracy better than 0.4 Da was achieved for all PT subunits in the molecular weight range of 11,000 to 27,000 Da. At this mass assignment accuracy level, the sequences of the PT subunits investigated in this study are easily determined based on molecular weight alone. The subunits 1, 2, and 5 of PT were observed to undergo oxidation under normal storage conditions as ammonium sulfate suspension at 2 to 8 degrees C. These oxidized subunits can be separated completely or partially by reverse-phase high-performance liquid chromatography (HPLC) from their native counterparts. For the determination of oxidation sites, the oxidized subunits and their nonoxidized counterparts were fraction collected, trypsin digested, and mapped by LC-MS. The oxidized peptides and their nonoxidized counterparts were further studied by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to confirm their identities. The methionines at position 212 of subunit 1, at position 89 of subunit 2, and at position 40 of subunit 5 were found to be the primary sites of oxidation.


Impact of UV-B radiation (290-320 nm) upon estuarine bacteria.
Effects of ultraviolet radiation on the development of metabolism of estuarine bacterial populations in laboratory microecosystems were studied. When compared with bacterial populations developing under an ultraviolet-deficient condition, the heterotrophic populations from microecosystems exposed to an ultraviolet-supplemented sprectrum displayed an overall decrease in total numbers, an increase in the proportion of pigmented cells, a decrease in the number of cellulolytic microorganisms and an increase in heterotrophic respiration. Ultraviolet radiation in the 290-320 nm waveband was the apparent stressful environmental parameter.


Correction: The effect of light wavelength on in vitro bilirubin photodegradation and photoisomer production.
Following publication of this article, the authors noticed that an incorrect affiliation was assigned to the author "Lucie Muchová". The original article has now been updated so that the author "Lucie Muchová" is associated with the "Institute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University, Kateřinská 32, 120 00 Prague, Czech Republic". This has been corrected in both the PDF and HTML versions of the article.


Some dynamic factors in compressive deformity of the cervical spinal cord.
An investigation into the relative elastic and non-elastic components of compressive deformity of the cervical spinal cord has been made. Sixteen patients were examined by computed myelography with the neck flexed and extended, and one fresh specimen of a human spinal cord was studied under reversible transverse compression with the specimen in a stretched and shortened state. In conditions of transverse compression cord tissue undergoes an alteration in viscoelastic properties, manifesting itself as reduced expansion of the compressed segment as the cord shortens, which in some cases is independent of whether the agent is seen to actually contact the cord. The presence of degenerative changes in cord substance probably accentuates this alteration in mechanical properties.


A hybrid plasmid formed by recombination of a virulence plasmid and a resistance plasmid in Klebsiella pneumoniae.
The emergence of multidrug-resistant (MDR) and hypervirulent Klebsiella pneumoniae (hvKP) facilitates simultaneous dissemination of virulence and resistance in a single event, which poses serious threat to public health. This study characterized the multidrug-resistant and moderately virulent ST11 K64 K. pneumoniae strain HB25-1 from a clinical case with microbiological and genomic approaches. Plasmids from strain HB25-1 were subjected to whole plasmid sequencing using both the Illumina NextSeq 500 sequencing platform and Nanopore MinION sequencer platforms. Klebsiella pneumoniae HB25-1 was subjected to a conjugation experiment and Galleria mellonella infection model to evaluate the transmission and virulence potential. We report the emergence of an ST11, serotype K64 K. pneumoniae isolate, which is resistant to third-generation cephalosporin and exhibited a moderate level of virulence. WGS revealed that this strain harboured a plasmid, pHB25-1, which carried multidrug resistance genes (blaDHA-1, qnrB4, dfrA12, aadA2, sul1, aac(3)-lld, blaTEM-1, mph(E)) and virulence-encoding genes (the regulator of mucoid phenotype A gene rmpA2 and the aerobactin gene cluster iutAiucABCD). Genomic analysis indicated that pHB25-1 was formed through co-integration of structural regions located in two different plasmids, enabling it to encode both resistance and virulent phenotypes. Findings in this study provide evidence of active plasmid evolution in K. pneumoniae and suggest that surveillance of multidrug-resistant and hypervirulent K. pneumoniae is urgently needed.


Transcriptome analysis in the silkworm Bombyx mori overexpressing piRNA-resistant Masculinizer gene.
Dosage compensation is a process that produces a similar expression of sex-linked and autosomal genes. In the silkworm Bombyx mori with a WZ sex-determination system, the expression from the single Z in WZ females matches that of ZZ males due to the suppression of Z-linked genes in males. A primary maleness determinant gene, Masculinizer (Masc), is also required for dosage compensation. In females, silkworm Piwi is complexed with the W chromosome-derived female-specific Feminizer (Fem) PIWI-interacting RNA (piRNA) and cleaves Masc mRNA. When Fem piRNA-resistant Masc cDNA (Masc-R) is overexpressed in both sexes, only female larvae are dead during the larval stage. In this study, transcriptome analysis was performed in neonate larvae to examine the effects of Masc-R overexpression on a global gene expression profile. Z-linked genes were globally repressed in Masc-R-overexpressing females due to force-driven dosage compensation. In contrast, Masc-R overexpression had little effect on the expression of Z-linked genes and the male-specific isoform of B. mori insulin-like growth factor II mRNA-binding protein in males, indicating that excessive Masc expression strengthens neither dosage compensation nor maleness in males. Fourteen genes were differentially expressed between Masc-R-overexpressing and control neonate larvae in both sexes, suggesting Masc functions other than dosage compensation and masculinization.


Ultrasound-Guided Electrocoagulation of Neovessels for Chronic Patellar Tendinopathy.
Chronic patellar tendinopathy remains a challenging problem. The first line of treatment is conservative; when this fails, surgical treatment is indicated. Several open and arthroscopic techniques have been described. We describe an alternative technique using ultrasound-guided electrocoagulation of neovessels that leaves the patellar tendon intact.


Ageing and the regulation of protein synthesis: a balancing act?
Ageing in diverse species ranging from yeast to humans is associated with extensive changes in both general and specific protein synthesis. Accumulating evidence now indicates that these alterations are not simply a corollary of the ageing process but, rather, they have a causative role in senescent decline. Indeed, interfering with mRNA translation significantly influences longevity. Interestingly, the mechanisms that control mRNA translation interface with intricate, conserved signalling pathways and specific conditions that regulate ageing, such as the insulin-insulin growth factor 1 signalling pathway and caloric restriction. This emerging relationship reveals that protein synthesis is a novel determinant of ageing in diverse organisms such as yeast, worms, flies and mice and can thus be considered as a universal component of the ageing process.


A Bacterial Chromosome Structuring Protein Binds Overtwisted DNA to Stimulate Type II Topoisomerases and Enable DNA Replication.
When DNA is unwound during replication, it becomes overtwisted and forms positive supercoils in front of the translocating DNA polymerase. Unless removed or dissipated, this superhelical tension can impede replication elongation. Topoisomerases, including gyrase and topoisomerase IV in bacteria, are required to relax positive supercoils ahead of DNA polymerase but may not be sufficient for replication. Here, we find that GapR, a chromosome structuring protein in Caulobacter crescentus, is required to complete DNA replication. GapR associates in vivo with positively supercoiled chromosomal DNA, and our biochemical and structural studies demonstrate that GapR forms a dimer-of-dimers that fully encircles overtwisted DNA. Further, we show that GapR stimulates gyrase and topo IV to relax positive supercoils, thereby enabling DNA replication. Analogous chromosome structuring proteins that locate to the overtwisted DNA in front of replication forks may be present in other organisms, similarly helping to recruit and stimulate topoisomerases during DNA replication.


Fracture of the penis. Case report.
A rare case of fracture of the penis is reported. Review of the literature shows only 58 previously reported cases. (Meares 1971) A simple method of treatment under local anaesthesia is described.


MK-801 alters the GABAA receptor complex and potentiates flurazepam's antiseizure efficacy.
MK-801 is an uncompetitive allosteric antagonist that interferes with glutamate-gated calcium ion conductance through the NMDA receptor-associated ionophore. In an outbred strain of mouse, MK-801 elicits episodes of explosive "popping" behaviors that may serve as a preclinical screening paradigm for novel antipsychotic medications. This investigation examined the effects of MK-801, at doses associated with the elicitation of popping, on the GABAA receptor complex in cerebral cortex, and flurazepam's ability to antagonize electrically precipitated seizures. Twenty four hours after MK-801 administration, there was an increased density of the radiolabeled antagonist-preferring conformation of the central benzodiazepine binding site and a potentiation of flurazepam's antiseizure efficacy. The data show that interference with NMDA receptor-mediated calcium ion conductance is associated with a relatively selective change in the GABAA receptor complex in cerebral cortex, and has functional behavioral consequences. Moreover, the data provide additional evidence for a delicate balance between GABAergic and glutamatergic transmission. Disturbance of this balance can have behavioral consequences for the animal.


Purification and characterization of enantioselective N-acetyl-β-Phe acylases from Burkholderia sp. AJ110349.
For the production of enantiopure β-amino acids, enantioselective resolution of N-acyl β-amino acids using acylases, especially those recognizing N-acetyl-β-amino acids, is one of the most attractive methods. Burkholderia sp. AJ110349 had been reported to exhibit either (R)- or (S)-enantiomer selective N-acetyl-β-Phe amidohydrolyzing activity, and in this study, both (R)- and (S)-enantioselective N-acetyl-β-Phe acylases were purified to be electrophoretically pure and determined the sequences, respectively. They were quite different in terms of enantioselectivities and in their amino acids sequences and molecular weights. Although both the purified acylases were confirmed to catalyze N-acetyl hydrolyzing activities, neither of them show sequence similarities to the N-acetyl-α-amino acid acylases reported thus far. Both (R)- and (S)-enantioselective N-acetyl-β-Phe acylase were expressed in Escherichia coli. Using these recombinant strains, enantiomerically pure (R)-β-Phe (>99% ee) and (S)-β-Phe (>99% ee) were obtained from the racemic substrate.


Bacteremia Secondary to Uncommon Gram-Negative Bacilli Transmitted From the Canine in a Patient With Multiple Myeloma.
Sphingobacterium multivorum is a gram-negative rod found in the environment and rarely associated with human infections. Sphingobacterium is the causative agent of infections in an immunocompromised host in most cases. We report a rare case of cellulitis in an immunocompromised host by Sphingobacterium multivorum.


Is calibration of the perception of length modality-independent?
Perception becomes increasingly scaled to environmental properties when feedback is provided about the perception of a given property. Understanding the process of calibration requires a description of the stimulation patterns to which perceivers become calibrated as a result of such feedback. Recent investigations using a transfer-of-calibration paradigm have shown that recalibration of the perception of length transfers from audition to touch. Such results have provided preliminary evidence that calibration of this property is modality-independent (i.e., that feedback about length calibrates perceivers to a modality-independent stimulation pattern). The experiment reported here provides a stronger test of this claim by demonstrating that perception transfers in both directions (i.e., from audition to touch, and vice versa). The results provide further evidence that calibration is modality-independent, and they are consistent with the more general proposal that the stimulation patterns that support perception are also modality-independent.


Different definitions of CpG island methylator phenotype and outcomes of colorectal cancer: a systematic review.
Contradictory results were reported for the prognostic role of CpG island methylator phenotype (CIMP) among colorectal cancer (CRC) patients. Differences in the definitions of CIMP were the most common explanation for these discrepancies. The aim of this systematic review was to give an overview of the published studies on CRC prognosis according to the different definitions of CIMP. A systematic literature search was performed in MEDLINE and ISI Web of Science for articles published until 3 April 2015. Data extraction included information about the study population, the definition of CIMP, and investigated outcomes. Thirty-six studies were included in this systematic review. Among them, 30 studies reported the association of CIMP and CRC prognosis and 11 studies reported the association of CIMP with survival after CRC therapy. Overall, 16 different definitions of CIMP were identified. The majority of studies reported a poorer prognosis for patients with CIMP-positive (CIMP+)/CIMP-high (CIMP-H) CRC than with CIMP-negative (CIMP-)/CIMP-low (CIMP-L) CRC. Inconsistent results or varying effect strengths could not be explained by different CIMP definitions used. No consistent variation in response to specific therapies according to CIMP status was found. Comparative analyses of different CIMP panels in the same large study populations are needed to further clarify the role of CIMP definitions and to find out how methylation information can best be used to predict CRC prognosis and response to specific CRC therapies.


High-quality read-based phasing of cystic fibrosis cohort informs genetic understanding of disease modification.
Phasing of heterozygous alleles is critical for interpretation of cis-effects of disease-relevant variation. We sequenced 477 individuals with cystic fibrosis (CF) using linked-read sequencing, which display an average phase block N50 of 4.39 Mb. We use these samples to construct a graph representation of CFTR haplotypes, demonstrating its utility for understanding complex CF alleles. These are visualized in a Web app, CFTbaRcodes, that enables interactive exploration of CFTR haplotypes present in this cohort. We perform fine-mapping and phasing of the chr7q35 trypsinogen locus associated with CF meconium ileus, an intestinal obstruction at birth associated with more severe CF outcomes and pancreatic disease. A 20-kb deletion polymorphism and a PRSS2 missense variant p.Thr8Ile (rs62473563) are shown to independently contribute to meconium ileus risk (p = 0.0028, p = 0.011, respectively) and are PRSS2 pancreas eQTLs (p = 9.5 × 10-7 and p = 1.4 × 10-4, respectively), suggesting the mechanism by which these polymorphisms contribute to CF. The phase information from linked reads provides a putative causal explanation for variation at a CF-relevant locus, which also has implications for the genetic basis of non-CF pancreatitis, to which this locus has been reported to contribute.


In Vitro Activity of Vancomycin, Teicoplanin, Linezolid and Daptomycin Against Methicillin-Resistant Staphylococcus aureus Isolates Collected from Chinese Hospitals in 2018-2020.
Vancomycin, teicoplanin, linezolid and daptomycin are four major antibacterials used for methicillin-resistant Staphylococcus aureus (MRSA) infection treatment. However, with the increasing failure of clinical MRSA anti-infective treatment, it is urgent to investigate the status of MRSA sensitivity to these four drugs. In the present study, 407 non-duplicated MRSA isolates from 6 provinces in China were collected from January 2018 to August 2020. The minimum inhibitory concentrations (MICs) of vancomycin, teicoplanin, linezolid and daptomycin were determined by broth microdilution method, and their MIC50, MIC90, and geometric mean MIC were calculated. All 407 MRSA strains were sensitive to these four antibacterials. MIC range of vancomycin, teicoplanin, linezolid and daptomycin was 0.25 to 2 mg/L, 0.125 to 4 mg/L, 0.25 to 4 mg/L and 0.06 to 1 mg/L, respectively. Between 2018 and 2020, there was no "MIC creep" in vancomycin, teicoplanin and daptomycin. The geometric mean MIC of linezolid was not increased, but both MIC50 and MIC90 in 2019 and 2020 MRSA isolates were higher than 2018 isolates. All MRSA isolates remained sensitivity to vancomycin, teicoplanin, linezolid and daptomycin. The linezolid MIC50 and MIC90 increased have been found in this study.


Association between maternal smoking during pregnancy and offspring overweight in U.S.-born children.
The criticism of the literature on smoking during pregnancy and offspring overweight was the confounding from postnatal factors. Interaction between gestational age and prenatal maternal smoking has not yet assessed. We used the Third National Health and Nutrition Examination Survey (1988-1994), linked with natality files of US-born singletons aged 2 to 6 years. A body mass index in the 85th percentile or higher were considered overweight, including obesity. Gestational age was dichotomized as preterm (<37 weeks, n = 240) or full-term (n = 2125). Smoking status during pregnancy was ascertained by a questionnaire-based interview during National Health and Nutrition Examination Survey. The prevalence of offspring overweight and obesity combined was 17.3% (SE = 1.3%). And 24.0% (1.3%) of mothers smoked while pregnant. A significant interaction was observed between maternal smoking and gestational age. In preterm children, a higher prevalence of overweight (34.3% [6.7%]) was found among the offspring of smoking mothers compared to non-smoking mothers (15.8% [3.6%]). After adjustment for socio-demographics, prenatal and postnatal factors, in preterm born offspring, the odds ratio of being born to smoking mothers was 2.46 (95% confidence intervals: 1.13-5.37) among children with overweight/obesity compared to children with healthy weight born to non-smoking mothers. In full-term children, the OR of being born to smoking mothers was 0.72 (0.50-1.03) among offspring with overweight/obesity relative to offspring with healthy weight born to non-smoking mothers. Maternal smoking during pregnancy was strongly associated with offspring overweight and obesity in preterm births after control for postnatal factors. Preterm children of smoking mothers should be prioritized for obesity prevention.


Vibrio metschnikovii, a Potential Pathogen in Freshwater-Cultured Hybrid Sturgeon.
In July 2021, a disease with a high mortality rate broke out in freshwater cultured hybrid sturgeon in Zhengzhou, Henan Province. A dominant strain, H-701, was isolated from diseased fish; physiological changes in diseased fish were investigated and molecular identification, biochemical characterization, and pathogenicity and drug sensitivity tests of H-701 were performed. The 16S rRNA gene sequence of H-701 was 99.86% homologous with that of Vibrio metschnikovii in GenBank. The 50% lethal dose of H-701 was 3.72 ± 0.929 × 104 CFU/g fish weight. The proportion of monocytes, neutrophils, and eosinophils in the blood of diseased sturgeon increased significantly, whereas the proportion of lymphocytes decreased. In diseased fish, the serum levels of total protein, albumin, globulin, and alkaline phosphatase decreased significantly, and those of aspartate aminotransferase, alanine aminotransferase, and complement C3 increased significantly. There were obvious pathological changes in several tissues of the diseased fish. H-701 was sensitive to antibiotics such as florfenicol, enrofloxacin, and doxycycline. This study not only demonstrated that V. metschnikovii was the cause of death of a large number of hybrid sturgeon but also revealed its potential risk in hybrid sturgeon aquaculture. The results provide a basis for the diagnosis and prevention of this disease.


Improved detection of diffuse large B-cell lymphoma by flow cytometric immunophenotyping-Effect of tissue disaggregation method.
Flow cytometric immunophenotyping (FCI) is recognized as a rapid, sensitive, and accurate method for diagnosis of B-cell lymphomas. We observed that FCI failed to identify the clonal B-cell population in several cases of large B-cell lymphoma (DLBCL) when tissue samples were prepared by a commercially available mechanical tissue disaggregation method. We tested a manual tissue disaggregation method and compared it with the mechanical method. FCI findings from 51 cases of DLBCL processed with the mechanical tissue disaggregation method, 27 cases processed using the manual method, and 15 cases processed using a combination of both methods were compared. The histological and immunohistochemical findings in each case were reviewed. FCI detected a clonal B-cell population in 88.9% of cases processed by the manual tissue disaggregation method, 66.7% of cases processed by a combination of the manual and mechanical disaggregation methods, and in 62.7% of cases processed solely by the mechanical tissue disaggregation method (P < 0.01 Fisher exact). Manual processing yielded positive FCI results in 81.8% of the nodal tissue samples and 93.8% of the extra-nodal tissue samples, whereas mechanical disaggregation was particularly inefficient in preserving large lymphoma cells from extra-nodal tissue: 71.4% of the nodal and 56.8% of the extra-nodal tissue samples processed by the mechanical method showed clonal B-cells by flow cytometry (P < 0.006, Fisher exact). The diagnostic yield of FCI in DLBCL can be significantly improved by utilizing a manual disaggregation method, particularly in extra-nodal tissue samples. © 2015 International Clinical Cytometry Society.


Ball mill abrasion test (BMAT): Method development and statistical evaluations.
High-stress abrasive wear is a major material consumption process in mining and ore beneficiation industries. The common laboratory high-stress abrasion apparatuses suffer from lack of capability of closely simulating the service conditions of grinding media and mill liners, being the main consumables in these sectors. The ball mill abrasion test (BMAT) is a versatile abrasive wear tester that facilitates reliable modelling of kinematics and contact mechanics of the industrial mills. Unlike 'standard' test devices, natural rocks of any type and/or blend with desired particles size distributions can be charged into the BMAT for testings under various ranges of liquids, grinding media and durations. It is simple to design, low-cost to manufacture, reliable to evaluate alloys performance and reproducible to rank abrasion-resistant materials. In this work, BMAT's two operation modes, BMAT-T (tumbling mode) and BMAT-C (cassette mode) are introduced. The performed comprehensive analysis on the method development, statistical assessment and further procedures refinement showed that:•In the BMAT-T, 20-hour tests using the planned operational parameters and normalisation method result in statistically reliable and reproducible outcomes.•In the BMAT-C, four 20-hr intervals, different operational parameters and specific specimen distribution pattern are needed to obtain high quality measurements.•The maximum observed relative standard deviation in the all statistical and alloy-performance evaluation campaigns was 6.6% - an excellent quality dimension for an abrasion test.


Effect of deoxynivalenol (DON) on growing pigs and its modification by modified yeast cell wall or modified yeast cell wall and bentonite.
The study examined effect of two adsorbents on the toxicity of Deoxynivalenol (DON) in growing pigs in a feeding trial. 24 male growing pigs (average initial body weight 11.5 kg) were assigned to one of six dietary treatments: control (uncontaminated diet); control + 0.5% adsorbent I; DON contaminated diet (1.73 mg/kg); DON contaminated diet + 0.5% adsorbent I; control + 0.5% adsorbent II and DON contaminated diet + 0.5% adsorbent II. Two digestibility trials were conducted on the second and fourth week of the feeding period with a sampling period of 7 days to determine the digestibility of the nutrients and the amounts of DON in faeces and urine. At the end of the experiments, the pigs were slaughtered, followed by blood haematology and biochemi analys. These data suggest that the addition of 0.5% modified yeast cell wall or a combination of modified yeast cell wall and bentonite to the naturally DON - contaminated diets reduce the effect of DON on the immune system of pigs but do not play an significant role in detoxification of DON in growing pigs.


Dataset of levels and masses of lipid species in healthy, asymptomatic and symptomatic leaves of vitis vinifera L. 'Malvasia fina' affected by ESCA complex disease.
The dataset presented in this paper comprises the masses of 208 lipid species and other compounds of lipid metabolism, and their levels in leaves of vines with brown wood streaking and grapevine leaf stripe, two symptomatic expressions of Esca complex disease (ESCA). Healthy, asymptomatic and symptomatic leaves were collected from the cultivar Malvasia Fina grown in a vineyard. The lipidome of these leaves was characterized using a platform consisting of an Ultrahigh Performance Liquid Chromatography and a Gas chromatography equipment coupled to a Q-Exactive Hybrid Quadrupole-Orbitrap high resolution/accurate Mass Spectrometer interfaced with a heated electrospray ionization source. The analysis permitted the detection of 158 molecular species of known identity and 50 species of unknown structural identity. The area counts of these molecular species is reported in the dataset, along with fold changes (log2-ratio), P-values (Welch's two-sample t-test), and q-values (false discovery rate) from all pairwise comparisons among experimental groups. These statistical data are intended to serve as means of identification for lipid species whose levels were altered by the disease, and which could be used as biomarkers of symptom emergence and disease progression. Because of few studies on the subject, the association between modulation of lipid biosynthetic pathways and disease progression in grapevine has remained poorly understood. The analysis of the data described here has already provided new perspectives regarding the pathogenesis of ESCA leaf symptom formation. Reanalysis of these data would undoubtedly unravel some physiological roles played by lipids in the adaptation of vine plants to stressful conditions.


Morphological Cell Profiling of SARS-CoV-2 Infection Identifies Drug Repurposing Candidates for COVID-19.
The global spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the associated disease COVID-19, requires therapeutic interventions that can be rapidly identified and translated to clinical care. Traditional drug discovery methods have a >90% failure rate and can take 10-15 years from target identification to clinical use. In contrast, drug repurposing can significantly accelerate translation. We developed a quantitative high-throughput screen to identify efficacious agents against SARS-CoV-2. From a library of 1,425 FDA-approved compounds and clinical candidates, we identified 17 dose-responsive compounds with in vitro antiviral efficacy in human liver Huh7 cells and confirmed antiviral efficacy in human colon carcinoma Caco-2, human prostate adenocarcinoma LNCaP, and in a physiologic relevant model of alveolar epithelial type 2 cells (iAEC2s). Additionally, we found that inhibitors of the Ras/Raf/MEK/ERK signaling pathway exacerbate SARS-CoV-2 infection in vitro. Notably, we discovered that lactoferrin, a glycoprotein classically found in secretory fluids, including mammalian milk, inhibits SARS-CoV-2 infection in the nanomolar range in all cell models with multiple modes of action, including blockage of virus attachment to cellular heparan sulfate and enhancement of interferon responses. Given its safety profile, lactoferrin is a readily translatable therapeutic option for the management of COVID-19.


Cumulus and granulosa cell markers of oocyte and embryo quality.
Lack of an objective, accurate, and noninvasive embryo assessment strategy remains one of the major challenges encountered in in vitro fertilization. Cumulus and mural granulosa cells reflect the characteristics of the oocyte, providing a noninvasive means to assess oocyte quality. Specifically, transcriptomic profiling of follicular cells may help identify biomarkers of oocyte and embryo competence. Current transcriptomics technologies include quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) for analysis of individual genes and microarrays and high-throughput deep sequencing for whole genome expression profiling. Recently, using qRT-PCR and microarray technologies, a multitude of studies correlated changes in cumulus or granulosa cell gene expression with clinically relevant outcome parameters, including in vitro embryo development and pregnancy. While the initial findings are promising, a clinical benefit from the use of identified biomarker genes remains to be demonstrated in randomized controlled trials.


Haemoglobin estimation--reliability of the copper sulphate specific gravity v. the cyanmethaemoglobin colorimetric method.
Automated colorimetric and copper sulphate (4 solutions with different specific gravities) methods were used to examine 218 blood specimens. The correlation between the two was high (r = 0.82)--proving that the copper sulphate method is reliable for haemoglobin screening. Copper sulphate gives better results in the higher haemoglobin region, which includes the majority of healthy people. In the lower haemoglobin region this method generally gives lower results than the cyanmethaemoglobin method. Copper sulphate is also by far the cheapest means currently available for mass screening.


Psychological predictors of prognosis in chronic heart failure.
Chronic heart failure (CHF) is an increasingly prevalent condition with high mortality and morbidity rates. This review examines the role of depression, anxiety, and social support on prognosis in CHF. Prospective studies that examined mortality as an outcome, and assessed depression, anxiety, or social support as associates were included. Methodological qualities were evaluated. In total, 25 studies were identified. Concerning depression, 6 of 15 studies of inpatients, 10 of 11 studies of outpatients, and 1 study of a mixed sample found associations between depression and prognosis, with greater associations rendered by depressive symptomatology in outpatients. Anxiety was not associated with prognosis in one inpatient study and one outpatient study. There was a univariable trend in one outpatient study for anxiety to be associated with prognosis. In two of six studies of inpatients and in two of four studies of outpatients, social support was associated with prognosis. On the basis of methodological quality, studies on depression showed mixed results, no conclusions could be drawn for anxiety because this association was not investigated soundly, and the quality of the social network was not associated with outcome. Evidence suggests that depressive symptoms and social support might be associated with prognosis in CHF outpatients, independently of biomedical risk factors. With respect to anxiety, no conclusions can be drawn. Future studies are warranted to disentangle associations with psychological factors.


Physiologic mastectomy via flank laparotomy.
Physiologic mastectomy can be used as a salvage procedure in cases of chronic suppurative mastitis, gangrenous mastitis, or chronic, severe mastitis associated with organisms liberating endotoxin or exotoxin. The surgical technique involves ligation of the major arterial blood supply (external pudendal artery) to the corresponding half of the mammary gland, which results in decreased systemic absorption of toxins and gland atrophy. The technique is performed with the cow standing, and it is relatively atraumatic. This procedure is a simple, yet effective alternative to radical mastectomy for unresponsive mastitis cases in genetically or otherwise valuable cattle.


Rapid WAVE dynamics in dendritic spines of cultured hippocampal neurons is mediated by actin polymerization.
The Wiskott-Aldrich syndrome protein family Verprolin-homologous protein (WAVE) complex has been proposed to link Rho GTPase activity with actin polymerization but its role in neuronal plasticity has never been documented. We now examined the presence, distribution and dynamics of WAVE3 in cultured hippocampal neurons. WAVE3 was localized to dendritic spines via its N-terminal domain. Green fluorescent protein (GFP)-tagged WAVE3 clusters demonstrate an F-actin-dependent high rate of local motility. Constitutive Rac activation translocates WAVE3 (via the N-terminus), to the leading edge of lamellipodia. Also, spinogenesis is associated with actin-based motility of the WAVE3 protein. Brain specific WAVE1 showed similar localization and effects on spine density. Cytoplasmic fragile X mental retardation protein interacting protein (CYFIP) and non-catalytic region of tyrosine kinase adaptor protein 1 (NCK-1), proteins that are assumed to complex with WAVE, have a somewhat similar cellular distribution and motility. We propose that the WAVE complex is a downstream effector of the Rac signaling cascade, localized to sites of novel synaptic contacts by means of its N-terminal domain, to guide local actin polymerization needed for morphological plasticity of neurons.


A monoclonal antibody directed against a conformational epitope of the HIV-1 trans-activator (Tat) protein neutralizes cross-clade.
The identification of a neutralizing mAb against extracellular HIV-1 transactivator of transcription (Tat) is important for the development of an efficient HIV-1 treatment. Tat plays an essential role in HIV-1 pathogenesis, not only for HIV-1 replication but also as an extracellular toxin able to disrupt the immune system. We showed previously that immunization of rabbits with Tat Oyi, a variant cloned from an African woman who did not develop AIDS following HIV-1 infection, raised antibodies able to recognize different Tat variants. We carried out mice immunization with Tat Oyi and selected a mAb named 7G12, which had the capacity to cross-recognize heterologous Tat variants by a common three-dimensional epitope. These results highlighted that Tat variants were able to acquire a structure, in contrast to a number of studies showing Tat as an unfolded protein. mAb 7G12 also had the capacity to neutralize the biological activities of these Tat variants by blocking the cellular uptake of extracellular Tat. This is the first study using Tat Oyi to produce a mAb able to neutralize effectively activities of extracellular Tats from different HIV-1 subtypes. This mAb has an important potential in therapeutic passive immunization and could help HIV-1 infected patients to restore their immunity.


Targeting thalamic tremor cells in deep brain stimulation for multiple sclerosis-induced complex tremor.
Tremor is an important cause of disability in patients with multiple sclerosis (MS). It is an ongoing debate as to which brain region should be targeted in MS patients with complex tremors. Here, we describe our experience with targeting thalamic tremor cells in the ventro-intermediate/ventro-oralis posterior (Vim/Vop) region in a patient with MS related complex tremor. Intraoperative multiple-microelectrode recordings showed the existence of tremor cells. Test stimulation produced the best effect when performed at the regions where tremor cells were recorded. Postoperative examination revealed a substantial improvement of the tremor. Our case observation reveals the existence of a neurophysiological target for deep brain stimulation (DBS) in MS related tremor.


(13C)-substituted sucrose: 13C-1H and 13C-13C spin coupling constants to assess furanose ring and glycosidic bond conformations in aqueous solution.
Sucrose (beta-D-fructofuranosyl alpha-D-glucopyranoside, 1), methyl alpha-D-fructofuranoside (2), and methyl beta-D-fructofuranoside (3) have been prepared by chemical and/or enzymic methods with single sites of 13C-substitution at C-1, C-2, C-3, and C-6 of the fructofuranosyl ring. 1H (500 MHz) and 13C (75 and 125 MHz) NMR spectra of 1-3 have been obtained, yielding 1H-1H, 13C-1H, and 13C-13C spin coupling constants that were used to assess furanose ring and glycoside bond conformations in aqueous (2H2O) solution. Results show that the conformational mobility of the furanosyl ring in 3 is altered when incorporated into 1. Furthermore, 13C-13C and 13C-1H spin couplings across the glycosidic linkage suggest a psi torsion angle different from that observed in the crystal (phi appears similar). Interplay between the strength of the exoanomeric effect and hydrogen bonding in solution may be responsible, in part, for the apparent conformational flexibility of 1. In addition, spin couplings in 2 and 3 have been compared to those measured previously in alpha-D-threo-pentulofuranose (4) and beta-D-threo-pentulofuranose (5), respectively, as a means to study the effect of glycosidation and hydroxymethyl substitution on the solution conformation of the 2-ketofuranose ring. The conversion of 4 to 2 is accompanied by minimal conformational change, whereas a significant change accompanies the conversion of 5 to 3, showing that the effect of substitution on ring conformation depends highly on ring configuration before and after substitution.


Using electronic audience response technology to track e-cigarette habits among college freshmen.
The use of e-cigarette devices, specifically JUUL, is on the rise on college campuses. Traditional means of collecting and analyzing research may not be fast enough for health professionals to effectively assess, plan, and implement effective prevention/intervention strategies. In August 2018, during incoming student orientation sessions at seven different college campuses, data was collected on a specific e-cigarette, JUUL. Data on use and knowledge of JUUL, as well as traditional cigarette use, was collected via immediate electronic audience response devices. Analyses included calculating descriptive statistics for questions of interest. Because response on each item was optional and anonymous, participation on specific questions varied and the total sample size for the questions of interest ranged from 1940 to 2027 students. Mean daily use rates were 13.7% (11.6-18.0%) for JUUL and 1.7% (1.3-2.5%) for cigarettes. Most students (67.3%) knew that JUUL always contained nicotine (38.4-84.5%), although 30.1% believed that it just contained nicotine and/or flavored vapor (15.5-50.0%), and 2.1% thought it was flavored vapor only (0.0-5.9%). This study reports the highest daily use of e-cigarettes among college students in the literature to date, with past-month e-cigarette use and daily cigarette use on par with previous estimates. Findings also highlight the knowledge gaps that some users have about JUUL specifically. In order for college health educators and professionals to best help students, adoption of methods that allow for more rapid assessment of e-cigarette trends is needed. This will help campuses more effectively address this issue, closing the research-to-practice gap in college health.


Anthropometry of pretarsal fullness and eyelids in oriental women.
In Chinese physiognomy, lower-lid pretarsal fullness is considered a sign of beauty in women. However, there are no data regarding the normal measurements of pretarsal fullness. The purpose of this study was to evaluate the average appearance of lower-lid pretarsal fullness in oriental women of specific age groups with the intention of obtaining data that surgeons could use when performing lower blepharoplasty. The effects of the orbicularis oculi muscle on pretarsal fullness are also discussed. A total of 260 oriental women were included in this study. The parameters of the eyelid, including the size of lower-lid pretarsal fullness, upper-lid crease, and palpebral fissure, were measured. The changes in these parameters with age, the ratio of lower-lid pretarsal fullness to palpebral fissure height, and the effect of the orbicularis oculi muscle on pretarsal fullness were analyzed. Two-hundred sixty women (520 eyes) were analyzed in the study. The average age of the participants was 39.3 years (range 21-60 years). The prevalence of static and dynamic pretarsal fullness was 19.2 and 74.0 %, respectively. The prevalence was higher in subjects in the fourth and fifth decades of their lives and lowest in subjects in their sixth decade. In the younger group, the average size of static pretarsal fullness was approximately 6.1-6.5 mm, and the static pretarsal fullness ratio was approximately 0.4. The vertical dimensions of static and dynamic pretarsal fullness increased with age. The changes were significantly higher in subjects over 20 years of age. This study provided data about the size and prevalence of pretarsal fullness, and allowed us to provide reference data for doctors to utilize when treating patients seeking lower-eyelid pretarsal fullness. Patients may appear younger when their new static pretarsal fullness falls within the range of 6.1-6.5 mm in the vertical dimension and when the pretarsal fullness ratio is about 0.4. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Transcriptome analysis of MAPK signaling pathway and associated genes to angiogenesis in chicken erythrocytes on response to thiram-induced tibial lesions.
This study was planned to investigate TD (Tibial dyschondroplasia) on the potential MAPK signaling pathway and angiogenesis related genes. Forty-eight broilers were allotted into control (C) and treatment (T) groups of 2, 6 and 15 days as C1, C2, C3, T1, T2 and T3. The histopathology results revealed that tibiotarsus bone of chickens had more lesions on day 6 (T2 group). The chondrocytes were disordered, and the size, shape and proliferation were affected. Transcriptome results revealed that differentially expressed genes (DEGs) identified were 63, 1026, 623, 130, 141 and 146 in C1 (2 days control vs 6 days control); C2 (2 days control vs 15 days control); C3 (6 days control vs 15 days control); T1 (2 days treatment vs 6 days treatment); T2 (2 days treatment vs 15 days treatment) and T3 (6 days treatment vs 15 days treatment) groups respectively. Whereas, 10 angiogenesis related-genes RHOC, MEIS2, BAIAP2, TGFBI, KLF2, CYR61, PTPN11, PLXNC1, HSPH1 and NRP2 were downregulated on day 6 in the treatment group. The pathway which was found enriched in the control and treatment groups was MAPK signaling pathway. Therefore selected 10 MAPK signaling pathway-related genes RAC2, MAP3K1, PRKCB, FLNB, IL1R1, PTPN7, RPS6KA, MAP3K6, GNA12 and HSPA8 which were found significantly downregulated in the treatment group on day 6. It is concluded that angiogenesis and MAPK signaling pathway related genes has an essential role in TD, as those top screened genes found downregulated in the thiram fed chickens when TD observed severed on day 6.


Hericium erinaceus potentially rescues behavioural motor deficits through ERK-CREB-PSD95 neuroprotective mechanisms in rat model of 3-acetylpyridine-induced cerebellar ataxia.
Cerebellar ataxia is a neurodegenerative disorder with no definitive treatment. Although several studies have demonstrated the neuroprotective effects of Hericium erinaceus (H.E.), its mechanisms in cerebellar ataxia remain largely unknown. Here, we investigated the neuroprotective effects of H.E. treatment in an animal model of 3-acetylpyridine (3-AP)-induced cerebellar ataxia. Animals administered 3-AP injection exhibited remarkable impairments in motor coordination and balance. There were no significant effects of 25 mg/kg H.E. on the 3-AP treatment group compared to the 3-AP saline group. Interestingly, there was also no significant difference in the 3-AP treatment group compared to the non-3-AP control, indicating a potential rescue of motor deficits. Our results revealed that 25 mg/kg H.E. normalised the neuroplasticity-related gene expression to the level of non-3-AP control. These findings were further supported by increased protein expressions of pERK1/2-pCREB-PSD95 as well as neuroprotective effects on cerebellar Purkinje cells in the 3-AP treatment group compared to the 3-AP saline group. In conclusion, our findings suggest that H.E. potentially rescued behavioural motor deficits through the neuroprotective mechanisms of ERK-CREB-PSD95 in an animal model of 3-AP-induced cerebellar ataxia.


High-SPEED super-resolution SPEED microscopy to study primary cilium signaling in vivo.
The primary cilium is a surface exposed organelle found in eukaryotic cells that functions to decode a variety of intracellular signals with significant implications in human developmental disorders and diseases. It is therefore highly desirable to obtain in vivo information regarding the dynamic processes occurring within the primary cilium. However, current techniques are limited by either the physical limitations of light microscopy or the static nature of electron microscopy. To overcome these limitations, single-point edge-excitation sub-diffraction (SPEED) microscopy was developed to obtain dynamic in vivo information in subcellular organelles such as cilia and nuclear pore complexes using single-molecule super-resolution light microscopy with a spatiotemporal resolution of 10-20nm and 0.4-2ms. Three-dimensional (3D) structural and dynamic information in these organelles can be further obtained through a post-processing 2D-to-3D transformation algorithm. Here we present a modular step-by-step protocol for studying primary cilium signaling dynamics, including Intraflagellar transport (IFT) via IFT20 and somatostatin g-protein-coupled receptor activity via SSTR3.