The Mammalian Ribo-interactome Reveals Ribosome Functional Diversity and Heterogeneity.

During eukaryotic evolution, ribosomes have considerably increased in size, forming a surface-exposed ribosomal RNA (rRNA) shell of unknown function, which may create an interface for yet uncharacterized interacting proteins. To investigate such protein interactions, we establish a ribosome affinity purification method that unexpectedly identifies hundreds of ribosome-associated proteins (RAPs) from categories including metabolism and cell cycle, as well as RNA- and protein-modifying enzymes that functionally diversify mammalian ribosomes. By further characterizing RAPs, we discover the presence of ufmylation, a metazoan-specific post-translational modification (PTM), on ribosomes and define its direct substrates. Moreover, we show that the metabolic enzyme, pyruvate kinase muscle (PKM), interacts with sub-pools of endoplasmic reticulum (ER)-associated ribosomes, exerting a non-canonical function as an RNA-binding protein in the translation of ER-destined mRNAs. Therefore, RAPs interconnect one of life's most ancient molecular machines with diverse cellular processes, providing an additional layer of regulatory potential to protein expression.

Transvaginal natural orifice transluminal endoscopic surgery for ectopic pregnancy.

AIMS: This study aims to describe our transvaginal natural orifice transluminal endoscopic surgery (vNOTES) technique for ectopic pregnancy that can be performed using conventional laparoscopic equipment with the addition of a self-constructed pessary port and to evaluate the safety, feasibility, and outcomes of the technique. METHODS: This is a retrospective study evaluating outcomes of patients who underwent vNOTES for ectopic pregnancy (n = 21) between August 2019 and April 2021. RESULTS: Twenty-one patients underwent vNOTES as intended without any intraoperative complications. Three patients (14.3%) were nulliparous, 16 patients (76.2%) had no history of vaginal delivery, and 13 patients (61.9%) had a history of at least one cesarean delivery. Eight patients (38.1%) had a history of previous abdominal surgery other than cesarean section. The mean duration of surgery was 43.4 ± 12.6 min. The mean visual analog scale scores for pain were 2.45 ± 1.13 at 2 h after surgery, 0.45 ± 0.83 at 12 h after surgery, and 0.18 ± 0.36 at 24 h after surgery. The median duration of postoperative hospital stay was 1 day (range, 1-2). There were no postoperative complications within 30 days after surgery. CONCLUSIONS: vNOTES can be performed in an existing laparoscopy setup with the addition of a self-constructed pessary port. vNOTES is a safe and effective surgical treatment option for ectopic pregnancy, even in patients who have not had a vaginal delivery and have had multiple abdominal surgeries.

Recurrent sigmoid volvulus: Cause of colon perforation, sepsis, and fetal death.

Sigmoid volvulus is one of the most common reasons for intestinal obstruction. Recurrent sigmoid volvulus occurred in only a few cases. Torsion of the sigmoid colon around the mesenteric portion initiates ischemia, gangrene, and perforation. Here, we presented a case with recurrent sigmoid volvulus. A 19-year-old Syrian refugee has been admitted to emergency room during 30th gestation week with acute abdomen, constipation, and lack of gas passage. She had a medical history of rectosigmoidoscopy and detorsion of sigmoid volvulus 6 days ago. Her vital signs showed tachycardia, hypotension, and tachypne, and her body temperature was 35.6°C. Sonography revealed nonviable fetus. Emergency laparotomy has been performed. Sigmoid volvulus and contaminated intraperitoneal area with feces was evaluated. A cesarean section, total colectomy, and end-ileostomy have been performed. Patient stayed 3 days in intensive care unit and was discharged on the 17th day. Sigmoid volvulus is a real emergency. Delayed treatment of sigmoid volvulus is related to maternal and fetal mortality.

Crucial role for DNA ligase III in mitochondria but not in Xrcc1-dependent repair.

Mammalian cells have three ATP-dependent DNA ligases, which are required for DNA replication and repair. Homologues of ligase I (Lig1) and ligase IV (Lig4) are ubiquitous in Eukarya, whereas ligase III (Lig3), which has nuclear and mitochondrial forms, appears to be restricted to vertebrates. Lig3 is implicated in various DNA repair pathways with its partner protein Xrcc1 (ref. 1). Deletion of Lig3 results in early embryonic lethality in mice, as well as apparent cellular lethality, which has precluded definitive characterization of Lig3 function. Here we used pre-emptive complementation to determine the viability requirement for Lig3 in mammalian cells and its requirement in DNA repair. Various forms of Lig3 were introduced stably into mouse embryonic stem (mES) cells containing a conditional allele of Lig3 that could be deleted with Cre recombinase. With this approach, we find that the mitochondrial, but not nuclear, Lig3 is required for cellular viability. Although the catalytic function of Lig3 is required, the zinc finger (ZnF) and BRCA1 carboxy (C)-terminal-related (BRCT) domains of Lig3 are not. Remarkably, the viability requirement for Lig3 can be circumvented by targeting Lig1 to the mitochondria or expressing Chlorella virus DNA ligase, the minimal eukaryal nick-sealing enzyme, or Escherichia coli LigA, an NAD(+)-dependent ligase. Lig3-null cells are not sensitive to several DNA-damaging agents that sensitize Xrcc1-deficient cells. Our results establish a role for Lig3 in mitochondria, but distinguish it from its interacting protein Xrcc1.

Current issues and future research priorities for health economic modelling across the full continuum of Alzheimer's disease.

Available data and models for the health-economic evaluation of treatment in Alzheimer's disease (AD) have limitations causing uncertainty to decision makers. Forthcoming treatment strategies in preclinical or early AD warrant an update on the challenges associated with their economic evaluation. The perspectives of the co-authors were complemented with a targeted review of literature discussing methodological issues and data gaps in AD health-economic modelling. The methods and data available to translate treatment efficacy in early disease into long-term outcomes of relevance to policy makers and payers are limited. Current long-term large-scale data accurately representing the continuous, multifaceted, and heterogeneous disease process are missing. The potential effect of disease-modifying treatment on key long-term outcomes such as institutionalization and death is uncertain but may have great effect on cost-effectiveness. Future research should give priority to collaborative efforts to access better data on the natural progression of AD and its association with key long-term outcomes.

DNA ligase III promotes alternative nonhomologous end-joining during chromosomal translocation formation.

Nonhomologous end-joining (NHEJ) is the primary DNA repair pathway thought to underlie chromosomal translocations and other genomic rearrangements in somatic cells. The canonical NHEJ pathway, including DNA ligase IV (Lig4), suppresses genomic instability and chromosomal translocations, leading to the notion that a poorly defined, alternative NHEJ (alt-NHEJ) pathway generates these rearrangements. Here, we investigate the DNA ligase requirement of chromosomal translocation formation in mouse cells. Mammals have two other DNA ligases, Lig1 and Lig3, in addition to Lig4. As deletion of Lig3 results in cellular lethality due to its requirement in mitochondria, we used recently developed cell lines deficient in nuclear Lig3 but rescued for mitochondrial DNA ligase activity. Further, zinc finger endonucleases were used to generate DNA breaks at endogenous loci to induce translocations. Unlike with Lig4 deficiency, which causes an increase in translocation frequency, translocations are reduced in frequency in the absence of Lig3. Residual translocations in Lig3-deficient cells do not show a bias toward use of pre-existing microhomology at the breakpoint junctions, unlike either wild-type or Lig4-deficient cells, consistent with the notion that alt-NHEJ is impaired with Lig3 loss. By contrast, Lig1 depletion in otherwise wild-type cells does not reduce translocations or affect microhomology use. However, translocations are further reduced in Lig3-deficient cells upon Lig1 knockdown, suggesting the existence of two alt-NHEJ pathways, one that is biased toward microhomology use and requires Lig3 and a back-up pathway which does not depend on microhomology and utilizes Lig1.

Chromosomal translocations induced at specified loci in human stem cells.

The precise genetic manipulation of stem and precursor cells offers extraordinary potential for the analysis, prevention, and treatment of human malignancies. Chromosomal translocations are hallmarks of several tumor types where they are thought to have arisen in stem or precursor cells. Although approaches exist to study factors involved in translocation formation in mouse cells, approaches in human cells have been lacking, especially in relevant cell types. The technology of zinc finger nucleases (ZFNs) allows DNA double-strand breaks (DSBs) to be introduced into specified chromosomal loci. We harnessed this technology to induce chromosomal translocations in human cells by generating concurrent DSBs at 2 endogenous loci, the PPP1R12C/p84 gene on chromosome 19 and the IL2Rgamma gene on the X chromosome. Translocation breakpoint junctions for t(19;X) were detected with nested quantitative PCR in a high throughput 96-well format using denaturation curves and DNA sequencing in a variety of human cell types, including embryonic stem (hES) cells and hES cell-derived mesenchymal precursor cells. Although readily detected, translocations were less frequent than repair of a single DSB by gene targeting or nonhomologous end-joining, neither of which leads to gross chromosomal rearrangements. While previous studies have relied on laborious genetic modification of cells and extensive growth in culture, the approach described in this report is readily applicable to primary human cells, including multipotent and pluripotent cells, to uncover both the underlying mechanisms and phenotypic consequences of targeted translocations and other genomic rearrangements.

Comparison of ankle force, mobility, flexibility, and plantar pressure values in athletes according to foot posture index.

Objectives: This study aims to compare ankle force, mobility, flexibility, and plantar pressure distribution of athletes according to foot posture index (FPI). Patients and methods: Between September 2016 and May 2018, a total of 70 volunteer male athletes (mean age: 21.1±2.3 years; range, 18 to 25 years) were included. The athletes were divided into three groups according to their FPI as follows: having supinated feet (Group 1, n=16), neutral/normal feet (Group 2, n=36), or pronated feet (Group 3, n=18). Ankle range of motion (ROM), muscle flexibility, ankle joint strength, and plantar pressure distribution were measured. Results: There were significant differences among the three groups in both right and left ankle dorsiflexion ROM (p=0.009 and p=0.003, respectively). Group 1 had significantly smaller dorsiflexion ROM than the other groups. Group 1 also showed significantly less flexibility in the gastrocnemius and soleus muscles than the other foot posture groups. Groups 2 and 3 exhibited significant differences in the maximum torque (p=0.018), maximum work (p=0.008), and total work (p=0.008) of the right plantar flexor muscles at 60°/sec angular velocity. Peak pressure measurements of the right foot were higher in Group 1, compared to Groups 2 and 3 (p<0.001). Conclusion: The results of this study may help to enhance athletic performance by providing a guide for designing training programs appropriate for athletes with different foot types to address their specific muscle flexibility and strength deficiencies.

Could Birth Weight to Placental Weight Ratio Predict Postpartum Haemorrhage and Neonatal Intensive Care Unit Admission?

OBJECTIVE: To evaluate the usability of the ratio of birth weight to placental weight [fetoplacental ratio (FPR)] in predicting postpartum haemorrhage (PPH) and neonatal intensive care unit (NICU) admission. STUDY DESIGN: Prospective observational study. PLACE AND DURATION OF STUDY: Bursa Yuksek Ihtisas Training & Research Hospital, Bursa, Turkey, between July 2020 and July 2021. METHODOLOGY: Women who were supposed to have an uncomplicated delivery with a live, single, term pregnancy without any concomitant disease, were included in the study. Patients with PPH were accepted as the study group and patients without PPH were the control group. For NICU requirement, babies who were admitted to NICU were the study group, and babies who did not require NICU were the control group. The fetoplacental ratio was calculated by dividing the newborn weight to placental weight and evaluated in the prediction of NICU admission and PPH. RESULTS: The number of patients included in the study was 812. Approximately 7% of women had postpartum haemorrhage. The FPR was found as an independent predictor for PPH by nearly 3.5 fold. Women who experienced PPH had heavier placenta and lower fetoplacental ratio. Patients whose babies were admitted to NICU also had lower FPR with statistically significant differences. CONCLUSION: The fetoplacental ratio could be a promising predictor for PPH and NICU admission in the postpartum period. Since novel studies are needed using ultrasonographic measurements during antenatal surveillance to predict PPH or NICU admission. KEY WORDS: Birth weight, Neonatal intensive care unit, Placental weight, Postpartum haemorrhage, Cesarean birth, Vaginal birth, Fetoplacental ratio.

Are women diagnosed with early pregnancy loss at risk for anxiety, depression, and perinatal grief?

OBJECTIVES: To examine the effects of early pregnancy loss on emotions such as depression, grief, or a sense of hopelessness, while investigating different types of diagnoses, hospital stays, and treatments. METHODS: A prospective cohort epidemiological study was carried out in Bursa Yuksek Ihtisas Training and Research Hospital, Bursa, Turkey, between January and September 2019. The study included women diagnosed with early pregnancy loss classified into 3 groups: missed abortus, anembryonic pregnancy, and spontaneous abortion. The patients were screened via the Spielberger state-anxiety inventory (STAI-1) before initiating treatment. The Edinburgh postpartum depression scale (EPDS) and Perinatal Grief Scale (PGS) were also carried out in the first week of their hospital discharge. RESULTS: The study was carried out with a total of 116 patients. The median gestational week of the patients was calculated at 9, their median hospital stay was 2 days, and their median dose of misoprostol was 800 mcg. The STAI-1 revealed that median values computed for women in all groups indicated moderate anxiety. The EDPS also demonstrated depression-positive median values for women in all 3 groups (EPDS>13). However, no statistically significant difference was noted in comparisons of the 3 groups apropos STAI-1, EPDS, and PGS. CONCLUSION: Moderate anxiety, depressed mood, and perinatal grief were found in women diagnosed with early pregnancy loss, regardless of the type of abortion.

Short interdelivery interval in modern obstetrics: Maternal and neonatal outcomes.

Objective: To investigate the maternal, neonatal outcomes of the patients with short interdelivery interval (IDI) considering initial pregnancy outcomes. Materials and Methods: Women with two consecutive deliveries between 2016 and 2020 were included in the study. The maternal and neonatal outcomes of both pregnancies were reviewed. The time interval between consecutive deliveries was calculated. The patients were divided into two groups in terms of IDI either less or more than 24 months. Results: The number of patients with short IDI (≤24 months), and normal IDI was 1.915 and 1.370, respectively. About 15% of the women in both groups had at least one obstetric morbidity. The rates of uterine rupture, placenta previa, and peripartum hysterectomy were higher in women with short IDI. The number of patients with low birth weight, very low birth weight, and stillbirth was higher in the short IDI group. Conclusion: Patients with short interpregnancy intervals should be considered high-risk pregnancy. Adequate contraceptive methods should be used to prevent unintended pregnancies.

Determinants of cesarean-related complications: high number of repeat cesarean, operation type or placental pathologies?

BACKGROUND: Cesarean delivery (CD) is one of the most common operations worldwide. Vaginal birth after cesarean (VBAC) could be a solution to decrease increased CD rates. On the other hand, risks of VBAC on maternal and neonatal outcomes drifts physicians and patients to a scheduled CD. Successive CDs, especially after the 3rd operation, increase complications for the fetus and the mother. Operation type (emergency or elective CD) could be a risk factor of increased morbidities, like placental implantation anomalies. Evaluation of these conditions related to complications and morbidities were investigated. Material and methods: Women who underwent the fourth and more repeat CD in Bursa Yuksek Ihtisas Training Research Hospital between March 2016 and December 2019 were retrospectively reviewed. Pre-operative characteristics, per-operative and post-operative complications were reviewed. Patients were separated into groups as operational type, repeat cesarean number, and major morbidities. A comparison between groups was evaluated. Results: A total of 46.048 women gave birth, of which 17,721 underwent CDs with a rate of 38%. The rate of primary CD was 18%. The number of the fourth or more CD performed was 854. The number of patients who underwent fourth and fifth or more CD and of these operational data could be accessed was 599 and 145, respectively. The overall complications were detected as severe adhesions (n: 220), preterm delivery (n: 91), stillbirth (n: 9), admission to NICU (n: 98), bladder injury (n: 10), uterine scar dehiscence (n: 6), uterine rupture (n: 6), uterine atony (n: 26), blood transfusion requirement (n: 68), preterm delivery (n: 91), placenta previa totalis (n: 24), morbidly adherent placenta (n: 14), hysterectomy (n: 12), partial uterine resection (n: 2), uterus-conserving interventions (n: 26). The number of patients with major morbidity was 105. Emergency cesarean performed in 339 of 744 patients. A comparison of the emergency cesarean group with elective repeat cesarean group revealed no significant difference in operative adverse outcomes. Comparing patients between 4th repeat CD with 5th and more CD revealed a significant difference in severe adhesion, morbidly adherent placenta and hysterectomy. Previa totalis were detected in 24 patients. All of them experienced major morbidity with 12 of them underwent hysterectomy. The rest of them performed Uterus-conserving treatments (B-Lynch Suture, Bacri Balloon, Hypogastric artery ligation ) and a total of 51 units of packed red blood cells and 32 units of Fresh Frozen Plasma were transfused to 9 (37%) of 24 patients. Conclusion: The major risk factor of the morbidity is placenta previa whose incidence has dramatically increased after 3rd cesarean. Emergency cesarean did not increase the complication rate in the present study. Fourth and more repeat CDs ought to be performed by experienced obstetricians in high-equipped tertiary hospitals.

Act of fibulin-1 in preeclamptic patients: can it be a predictive marker?

Preeclampsia is one of the leading causes of maternal-neonatal morbidity and mortality, especially in developed and developing countries. Incidence of preeclampsia differs in accordance with parity, race, age, geography, and concomitant diseases. The role of placental implantation and risk factors was elucidated precisely. Antenatal care, use of medications, change in lifestyle, and nutritional supplementation were investigated for the prevention or decrease the complications; however, to date, there has not exposed a proper approach for prevention and prediction. The trigger mechanism or circumstance is still debate. Placental development especially spiral artery remodeling might be supposed to be the accused primary site of preeclampsia. Extracellular matrix proteins play a crucial role in implantation. Fibulin is one of these proteins which represents an association with matrix proteins, basement membranes, and elastic fibers. Fibulins are mainly functioning in the remodeling of tissues especially blood vessels, endocardial cushion, the mesenchymal, and connective tissue of several organs including heart, lung, intestine, kidneys, and liver. Several diseases were associated with altered fibulin levels. We aimed to examine fibulin-1 levels in preeclamptic patients and to focus on the possible role of fibulin-1 in preeclampsia. MATERIAL AND METHOD: A prospective observational, case-control study was achieved. Patients diagnosed with preeclampsia and healthy controls were recruited in the study. Patients' demographic features, perinatal outcomes, complications, obstetrics doppler ultrasonographic evaluations, laboratory results, and serum fibulin-1 levels were reviewed. The comparison of the groups was determined statistically. Correlation analysis and multivariate logistic analysis were calculated. The receiver operating characteristic (ROC) curve was used to indicate fibulin-1 levels for the prediction of preeclampsia. RESULTS: A total of 36 healthy pregnant and 38 preeclamptic patients were included in the study. Comparison of the groups with age, gravidity, BMI, APGAR scores, birth weight did not differ significantly. Kidney and liver function tests and complete hemogram parameters did not have a clinically important difference. Fibulin-1 levels were significantly lower in patients with preeclampsia. The ROC curve for fibulin-1 for predicting the preeclampsia risk was analyzed. The area under the ROC curves was 0.682 (95% CI [0.560-0.804, p < .007) for fibulin-1. The optimal cutoff value of fibulin-1 for detecting preeclampsia was ≤ 27.81 ng/ml, at which the sensitivity was 61.1% and specificity was 63.2 %. CONCLUSION: Fibulin-1 levels could be a beneficial marker for preeclampsia diagnosis and prediction. It might have a role in the etiopathology of preeclampsia, due to its function in the extracellular matrix.

Do patients with a single abnormal OGTT value need a globally admitted definition such as "borderline GDM"? Pregnancy outcomes of these women and the evaluation of new inflammatory markers.

INTRODUCTION: One of the approaches to diagnose Gestational Diabetes Mellitus (GDM) is to detect two or more elevated values in 3-h Glucose Tolerance Test (OGTT) after an abnormal 50 gr Glucose Challenge Test (GCT). Patients with single elevated OGTT generally postulated as healthy; however, these patients could experience adverse perinatal and maternal issues more frequently. We aimed to investigate the maternal and neonatal outcomes of women with single abnormal OGTT primarily by comparing these women with healthy controls and GDM patients. Secondarily; Mean Platelet Volume (MPV), Platelet Distribution Width (PDW), Neutrophil to Lymphocyte Ratio (NLR) and Platelet to Lymphocyte Ratio (PLR) which were defined as novel inflammatory markers recently, were evaluated among these women within the first trimester and before delivery values whether these markers could use as a predictive marker of GDM. MATERIALS AND METHODS: A retrospective cohort study was achieved in Bursa Yuksek Ihtisas Education and Training Hospital between January 2016 and April 2020. Patients who had GCT and OGTT at 24th-28th weeks of gestation were reviewed. Patients with GDM, women with single elevated OGTT value, and women with normal OCT values were recruited at the study as groups 1, 2, and 3 respectively. Maternal-neonatal outcomes and postpartum complications were reviewed from hospital registry system. Each complication were accumulated in a group entitled peripartum complication (a patient who had more than 1 complication for example preeclampsia and acute fetal distress was added in the peripartum complication group as one patient).The novel inflammatory markers were evaluated as NLR and PLR, and thrombocyte parameters as MPV and PDW were compared within the groups, and between the groups individually in the time period of first trimester and before delivery. RESULTS: A total of 10,579 patients were screened with OCT, of these a total of 1718 patients' results were between 140 mg/dl and 199 mg/dl. The numbers of the women who diagnosed GDM and who had single elevated OGTT were 508 and 469 respectively. Numbers of the patients who gave birth in our hospital and whose data were reviewed adequately were 464 in groups 1, 406 in group 2, and 768 in group 3.Patients with single elevated OGTT had increased rates of peripartum complication, acute fetal distress (AFD), IUGR, preterm delivery, cesarean delivery rate, macrosomia, labor arrest, blood component transfusion, post-partum complication and stillbirth than healthy controls. Statistical analysis of comparison between group 2 and 3 has revealed that; patients with single elevated OGTT had more peripartum complication (p = .032; odds ratio [OR] = 1.2, 95% CI: 1.02-1.54), had more babies with macrosomia (p < .001; [OR] = 1.7, 95% CI: 1.2-2.4), had more postpartum complication (p = .040; [OR] = 3, 95% CI: 0.997-9.1), and had higher cesarean rates (p < .001; [OR] = 1.29, 95% CI: 1.1-1.4).Evaluating the first trimester CBC parameters between groups; only PLR differed statistically significant in GDM patients. These parameters before delivery were also analyzed PLR and NLR values did not differ between all groups, on the other hand; MPV values were higher and PDW values were lower in healthy controls comparing GDM and single elevated OGTT group. CONCLUSION: Patients with single elevated OGTT had a higher risk of maternal and neonatal consequences than women with normal OCT, which was comparable levels to patients with GDM. These patients should not be underestimated and could be classified as an individual diagnose such as "Borderline GDM." To intervene in these patients with dietary advice and lifestyle changes like exercise could decrease neonatal and maternal adverse outcomes.

Double-Binding Botulinum Molecule with Reduced Muscle Paralysis: Evaluation in In Vitro and In Vivo Models of Migraine.

With a prevalence of 15%, migraine is the most common neurological disorder and among the most disabling diseases, taking into account years lived with disability. Current oral medications for migraine show variable effects and are frequently associated with intolerable side effects, leading to the dissatisfaction of both patients and doctors. Injectable therapeutics, which include calcitonin gene-related peptide-targeting monoclonal antibodies and botulinum neurotoxin A (BoNT/A), provide a new paradigm for treatment of chronic migraine but are effective only in approximately 50% of subjects. Here, we investigated a novel engineered botulinum molecule with markedly reduced muscle paralyzing properties which could be beneficial for the treatment of migraine. This stapled botulinum molecule with duplicated binding domain-binary toxin-AA (BiTox/AA)-cleaves synaptosomal-associated protein 25 with a similar efficacy to BoNT/A in neurons; however, the paralyzing effect of BiTox/AA was 100 times less when compared to native BoNT/A following muscle injection. The performance of BiTox/AA was evaluated in cellular and animal models of migraine. BiTox/AA inhibited electrical nerve fiber activity in rat meningeal preparations while, in the trigeminovascular model, BiTox/AA raised electrical and mechanical stimulation thresholds in Aδ- and C-fiber nociceptors. In the rat glyceryl trinitrate (GTN) model, BiTox/AA proved effective in inhibiting GTN-induced hyperalgesia in the orofacial formalin test. We conclude that the engineered botulinum molecule provides a useful prototype for designing advanced future therapeutics for an improved efficacy in the treatment of migraine.

Developmental differences of kinematic and muscular activation patterns in instep soccer kick.

Kinematic and neuromuscular activity differences amongst soccer players in different age groups were examined in this study. Thirty male soccer players evenly divided into three age groups (Group 1: age 12-13; Group 2: age 14-15; Group 3: age 16-17) were asked to perform instep kicks towards a target 11 m away. Their anthropometrics, instep kick kinematics, resultant ball velocities, both legs isokinetic strength, and electromyography (EMG) during kicking were compared amongst the three age groups. There were significant differences in height, body mass, body mass index, ball velocities, and isokinetic strength values amongst three age groups. Also, kicking kinematics including angular and linear velocities of hip, knee, ankle, and toe were significantly different (p < 0.05) amongst groups in several kicking phases. Furthermore, the activities of m. rectus femoris, m. vastus medialis, m. biceps femoris were significantly different amongst groups (p < 0.05). The ball velocities and leg strength parameters increased with age, neuromuscular activations, and kinematic parameters differed especially in leg-coking and forward swing phase of instep soccer kick. It should be concluded that an increase of resultant ball velocity of the instep kick is closely associated with chronical age, the development of leg muscle strength, and the neuromuscular activity of the kicking leg.

Duplication of clostridial binding domains for enhanced macromolecular delivery into neurons.

Neurological diseases constitute a quarter of global disease burden and are expected to rise worldwide with the ageing of human populations. There is an increasing need to develop new molecular systems which can deliver drugs specifically into neurons, non-dividing cells meant to last a human lifetime. Neuronal drug delivery must rely on agents which can recognise neurons with high specificity and affinity. Here we used a recently introduced 'stapling' system to prepare macromolecules carrying duplicated binding domains from the clostridial family of neurotoxins. We engineered individual parts of clostridial neurotoxins separately and combined them using a strong alpha-helical bundle. We show that combining two identical binding domains of tetanus and botulinum type D neurotoxins, in a sterically defined way by protein stapling, allows enhanced intracellular delivery of molecules into neurons. We also engineered a botulinum neurotoxin type C variant with a duplicated binding domain which increased enzymatic delivery compared to the native type C toxin. We conclude that duplication of the binding parts of tetanus or botulinum neurotoxins will allow production of high avidity agents which could deliver imaging reagents and large therapeutic enzymes into neurons with superior efficiency.

Maintenance electroconvulsive therapy combined with long-acting risperidone in the treatment of resistant bipolar affective disorder.

Maintenance electroconvulsive therapy is used for refractory bipolar disorder. We present a middle-aged man with refractory bipolar disorder who was successfully treated with maintenance electroconvulsive therapy and long-acting risperidone.

Prediction of neonatal respiratory distress syndrome via pulmonary artery Doppler examination.

OBJECTIVE: We aimed with this study to evaluate the role of pulmonary artery acceleration time to ejection time ratio (PATET) in the prediction of respiratory distress syndrome (RDS) in preterm neonates. MATERIALS AND METHODS: In this prospective cohort study, 105 singleton pregnant women with no congenital abnormalities and pregnancy complications who delivered before 37 weeks of gestational age were included. All the patients underwent ultrasound examination to obtain fetal pulmonary artery Doppler. 15 patients were excluded from the study as they did not give birth within 3 days subsequent to ultrasound examination, or inadequate Doppler measurements. After delivery the neonates were grouped according to diagnosis of RDS as RDS + and RDS-. RESULTS: One hundred five women met the inclusion criteria. Regarding the Doppler findings; only the PATET ratio was significantly different between the groups (0.2965 ± 0.042 versus 0.386 ± 0.068 p < .001, Z = -5.206). There was an inverse correlation between the diagnosis of RDS in the neonates and the PATET values, even after adjusted for gestational age estimated fetal weight and fetal gender (r = -0.52 and p = .0017). A cut-off value of 0.327 provided optimal specificity of 77.1%, a sensitivity of 90.9%, a negative predictive value of 95.4%, and a positive predictive value 52.7%. CONCLUSIONS: In consideration of these results fetal PATET ratio is a promising noninvasive tool to predict RDS in cases of preterm deliveries.

A genetic approach to study polyubiquitination in Saccharomyces cerevisiae.

Ubiquitin has seven lysines, all of which are used to generate polyubiquitin chains in the yeast Saccharomyces cerevisiae. While the biology associated with chains formed through lysines 48 and 63 is well studied, other chain types are more poorly characterized. We outline a methodology for using synthetic genetic analysis to examine ubiquitin mutants. Ubiquitin is encoded by four loci, necessitating several alterations to standard protocols, including the use of the SK1 strain background, which sporulates with very high efficiency. The methods described here could be used to examine other ubiquitin mutants, including those that do not support viability.