A foodborne outbreak of Norwalk virus gastroenteritis. Evidence for post-recovery transmission.
From November 10-16, 1982, 220 (57%) of 383 attendees at eight banquets for which food had been prepared at a single hotel restaurant and the employees of the hotel had onset of Norwalk virus gastroenteritis. Epidemiologic investigation of the three largest banquets confirmed consumption of potato and fruit salads (banquet A), coleslaw (banquet B), and tossed salad (banquet C) to be significantly associated with illness. Between November 8-19, similar illness occurred in seven (54%) of 13 hotel kitchen employees. The foods implicated in banquets A and B were prepared by one salad worker during her acute illness and up to 48 hours following her recovery. A second salad worker prepared the implicated tossed salad for banquet C 24 hours following her recovery. To the authors' knowledge, this is the first foodborne outbreak investigation demonstrating Norwalk viral excretion and transmission by a food handler after recovery from illness and either person-to-person or vehicle-borne transmission between food handlers with subsequent transmission by more than one food handler to patrons.


Placental transfer of cholesterol-4-14C into rabbit and guinea pig fetus.
A tracer dose of cholesterol-4-(14)C was given daily in the diet of six pregnant guinea pigs to establish an isotopic steady state. At the time of parturition, maternal and fetal blood and fetal tissues were collected and analyzed for cholesterol content and cholesterol specific activity. A comparison of these specific activities in neonatal and maternal serum indicated that about 22% of the fetal serum cholesterol was transferred from maternal blood. In the newborn, tissues generally had the same cholesterol specific activity as serum. Brain tissue was an exception in having a specific activity only 8.4% of that of serum. Dietary cholesterol did not increase serum cholesterol levels in the newborn but did increase the percentage of fetal cholesterol derived from the maternal circulation. The rapid transfer of cholesterol-4-(14)C across the placenta was indicated by the appearance of this isotope in the newborn 2 days after its administration to pregnant rabbits. A considerable amount of the cholesterol content of newborn guinea pigs and rabbits originated from the maternal blood.


Spinal cord injury and diaphragm neuromotor control.
Introduction: Neuromotor control of diaphragm muscle and the recovery of diaphragm activity following spinal cord injury have been narrowly focused on ventilation. By contrast, the understanding of neuromotor control for non-ventilatory expulsive/straining maneuvers (including coughing, defecation, and parturition) is relatively impoverished. This variety of behaviors are achieved via the recruitment of the diverse array of motor units that comprise the diaphragm muscle.Areas covered: The neuromotor control of ventilatory and non-ventilatory behaviors in health and in the context of spinal cord injury is explored. Particular attention is played to the neuroplasticity of phrenic motor neurons in various models of cervical spinal cord injury.Expert opinion: There is a remarkable paucity in our understanding of neuromotor control of maneuvers in spinal cord injury patients. Dysfunction of these expulsive/straining maneuvers reduces patient quality of life and contributes to severe morbidity and mortality. As spinal cord injury patient life expectancies continue to climb steadily, a nexus of spinal cord injury and age-associated comorbidities are likely to occur. While current research remains concerned only with the minutiae of ventilation, the major functional deficits of this clinical cohort will persist intractably. We posit some future research directions to avoid this scenario.


Interventions Within the Scope of Occupational Therapy to Improve Cognitive Performance for Individuals with Dementia and Mild Cognitive Impairment (2018-2022).
Systematic review briefs provide a summary of the findings from systematic reviews evaluated in conjunction with the American Occupational Therapy Association's Evidence-Based Practice Program. Each systematic review brief summarizes the evidence on a theme related to a systematic review topic. This systematic review brief presents findings related to interventions to improve cognitive function for individuals living with Alzheimer's disease and related dementias and mild cognitive impairment.


Benefits of positive relationship experiences for avoidantly attached individuals.
Attachment avoidance is characterized by discomfort with closeness and a reluctance to develop intimacy with romantic partners, which contribute to heightened general negativity and lower satisfaction and self-disclosure in and out of their relationships. Recent research, however, has begun to uncover circumstances in which romantic partners and positive relationships buffer more avoidantly attached individuals against deleterious individual and relationship outcomes. Across 3 studies, using a multimethod approach encompassing both experimental and dyadic longitudinal diary methods, we investigated the effects of positive, intimacy-related relationship experiences on more avoidant persons' positive and negative affect, relationship quality, self-disclosure, and attachment security immediately and over time. Results revealed that more avoidant individuals exhibit a reduction of general negative affect in particular (Studies 1-2) and report greater relationship quality (Studies 2-3) in response to positive relationship experiences, and, following intimacy-promoting activities with their partner, engage in greater self-disclosure over time and demonstrate decreased attachment avoidance 1 month later (Study 3). These findings identify novel circumstances in which more avoidant persons' negative expectations of relationships may be countered, and suggest that relatively simple techniques can have potentially important short- and long-term implications for more avoidant individuals and their relationships. (PsycINFO Database Record


Choices of Therapeutic Strategies for Colorectal Liver Metastases Among Expert Liver Surgeons: A Throw of the Dice?
To test the degree of agreement in selecting therapeutic options for patients suffering from colorectal liver metastasis (CRLM) among surgical experts around the globe. Only few areas in medicine have seen so many novel therapeutic options over the past decades as for liver tumors. Significant variations may therefore exist regarding the choices of treatment, even among experts, which may confuse both the medical community and patients. Ten cases of CRLM with different levels of complexity were presented to 43 expert liver surgeons from 23 countries and 4 continents. Experts were defined as experienced surgeons with academic contributions to the field of liver tumors. Experts provided information on their medical education and current practice in liver surgery and transplantation. Using an online platform, they chose their strategy in treating each case from defined multiple choices with added comments. Inter-rater agreement among experts and cases was calculated using free-marginal multirater kappa methodology. A similar, but adjusted survey was presented to 60 general surgeons from Asia, Europe, and North America to test their attitude in treating or referring complex patients to expert centers. Thirty-eight (88%) experts completed the evaluation. Most of them are in leading positions (92%) with a median clinical experience of 25 years. Agreement on therapeutic strategies among them was none to minimal in more than half of the cases with kappa varying from 0.00 to 0.39. Many general surgeons may not refer the complex cases to expert centers, including in Europe, where they also engage in complex liver surgeries. Considerable inconsistencies of decision-making exist among expert surgeons when choosing a therapeutic strategy for CRLM. This might confuse both patients and referring physicians and indicate that an international high-level consensus statements and widely accepted guidelines are needed.


A brain-penetrant microtubule-targeting agent that disrupts hallmarks of glioma tumorigenesis.
Glioma is sensitive to microtubule-targeting agents (MTAs), but most MTAs do not cross the blood brain barrier (BBB). To address this limitation, we developed the new chemical entity, ST-401, a brain-penetrant MTA. Synthesis of ST-401. Measures of MT assembly and dynamics. Cell proliferation and viability of patient-derived (PD) glioma in culture. Measure of tumor microtube (TM) parameters using immunofluorescence analysis and machine learning-based workflow. Pharmacokinetics (PK) and experimental toxicity in mice. In vivo antitumor activity in the RCAS/tv-a PDGFB-driven glioma (PDGFB-glioma) mouse model. We discovered that ST-401 disrupts microtubule (MT) function through gentle and reverisible reduction in MT assembly that triggers mitotic delay and cell death in interphase. ST-401 inhibits the formation of TMs, MT-rich structures that connect glioma to a network that promotes resistance to DNA damage. PK analysis of ST-401 in mice shows brain penetration reaching antitumor concentrations, and in vivo testing of ST-401 in a xenograft flank tumor mouse model demonstrates significant antitumor activity and no over toxicity in mice. In the PDGFB-glioma mouse model, ST-401 enhances the therapeutic efficacies of temozolomide (TMZ) and radiation therapy (RT). Our study identifies hallmarks of glioma tumorigenesis that are sensitive to MTAs and reports ST-401 as a promising chemical scaffold to develop brain-penetrant MTAs.


The anti-inflammation effect of Moutan Cortex on advanced glycation end products-induced rat mesangial cells dysfunction and High-glucose-fat diet and streptozotocin-induced diabetic nephropathy rats.
Moutan Cortex (MC, family: Paeonia suffruticosa Andr.) is a well-known traditional herbal medicine that has been shown to hold a protective effect on inflammation in several diseases. However, its anti-inflammatory activity on diabetic nephropathy (DN) has been less reported. The present study was conducted to evaluate the potential attenuation activities of MC on inflammation in AGEs-induced rat mesangial cells dysfunction and high-glucose-fat diet and streptozotocin (STZ)-induced DN rats and explore the possible mechanism underlying its DN effect. The inflammation in mesangial cells (HBZY-1) was induced by 200 μg/ml advanced glycation end products (AGEs). DN rats model was established by an administration high-glucose-fat diet and an intraperitoneal injection of STZ (30 mg/kg). Interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) level in cell supernatant and rats serum were detected by appropriate kits. A co-culture system of mesangial cells and macrophages was performed to evaluate the migration of macrophages. Immunohistochemical assay was applied to examine transforming growth factor beta1 (TGF-β1), IL-6, MCP-1 and intercellular adhesion molecule-1 (ICAM-1) expression in kidney tissues of rats. Furthermore, western blot analysis was carried out to examine TGF-β1, IL-6, MCP-1, ICAM-1 and RAGE protein expressions in mesangial cells. Pretreatment with MC could significantly inhibit AGEs-induced migration of macrophages in the co-culture system of mesangial cell and macrophage. MC could decrease IL-6 and MCP-1 levels in serum of DN rats in a dose-dependent manner. Furthermore, MC also improved the blood glucose, serum creatinine and urine protein levels. Both immunocytochemistry analysis and western blot analysis showed that MC decreased significantly the over-expression of IL-6, MCP-1, TGF-β1, ICAM-1 and RAGE in mesangial cells or kidney tissues. Additionally, the protein expression of proinflammatory cytokine could also be down-regulated by the pretreatment of RAGE-Ab (5 μg/ml). These findings indicated that the extract of MC had an amelioration activity on the inflammation in AGEs-induced mesangial cells dysfunction and high-glucose-fat diet and STZ-induced DN rats. The protective effect might be associated with the intervention of MC via target of RAGE. These findings suggested that MC might be a benefit agent for the prevention and treatment of DN.


Optimization of combined electron and photon beams for breast cancer.
Recently, intensity-modulated radiation therapy and modulated electron radiotherapy have gathered a growing interest for the treatment of breast and head and neck tumours. In this work, we carried out a study to combine electron and photon beams to achieve differential dose distributions for multiple target volumes simultaneously. A Monte Carlo based treatment planning system was investigated, which consists of a set of software tools to perform accurate dose calculation, treatment optimization, leaf sequencing and plan analysis. We compared breast treatment plans generated using this home-grown optimization and dose calculation software for different treatment techniques. Five different planning techniques have been developed for this study based on a standard photon beam whole breast treatment and an electron beam tumour bed cone down. Technique 1 includes two 6 MV tangential wedged photon beams followed by an anterior boost electron field. Technique 2 includes two 6 MV tangential intensity-modulated photon beams and the same boost electron field. Technique 3 optimizes two intensity-modulated photon beams based on a boost electron field. Technique 4 optimizes two intensity-modulated photon beams and the weight of the boost electron field. Technique 5 combines two intensity-modulated photon beams with an intensity-modulated electron field. Our results show that technique 2 can reduce hot spots both in the breast and the tumour bed compared to technique 1 (dose inhomogeneity is reduced from 34% to 28% for the target). Techniques 3, 4 and 5 can deliver a more homogeneous dose distribution to the target (with dose inhomogeneities for the target of 22%, 20% and 9%, respectively). In many cases techniques 3, 4 and 5 can reduce the dose to the lung and heart. It is concluded that combined photon and electron beam therapy may be advantageous for treating breast cancer compared to conventional treatment techniques using tangential wedged photon beams followed by a boost electron field.


An alternative spliced UPF2 transcript in pancreatic inflammatory myofibroblastic tumors.
Inflammatory myofibroblastic tumors (IMTs) are characterized by myofibroblast proliferation and an inflammatory cell infiltrate. Our previous study on IMTs reveals that disrupt NMD pathway causes to lower the threshold for triggering the immune cell infiltration, thereby resulting in inappropriate immune activation. However, myofibroblast differentiation and proliferation is not yet known. RT-PCR, RT-qPCR, DNA sequence, western bolt, 5'race analysis and site-specific mutagenesis were used in this study. Here, an alternative spliced (ALS) UPF2 mRNA skipping exon 2 and 3 and corresponding to the truncated UPF2 protein were found in 2 pancreatic IMTs. We showed that the uORF present in the 5'UTR of UPF2 mRNA is responsible for the translation inhibition, whiles ALS UPF2 is more facilitated to be translated into the truncated UPF2 protein. Several mRNA targets of the NMD were upregulated in IMT samples, indicating that the truncated UPF2 function is strongly perturbed, resulted in disrupted NMD pathway in IMTs. These upregulated NMD targets included cdkn1a expression and the generation of high levels of p21 (waf1/cip1), which may contribute to triggering IMTs. The disrupt UPFs/NMD pathway may link to molecular alteration associated with differentiation and proliferation for IMTs.


Sinus bradycardia with haemodynamic compromise following lithium intoxication.
Lithium is a well-established treatment for mood disorders and considered first-line pharmacological therapy for bipolar disorder as per the American Psychiatric Association guidelines. However, lithium is associated with significant toxicity. Cardiotoxicity including sinus node dysfunction is a rare but clinically significant presentation of lithium intoxication. This case report describes an adult male presenting with unstable sinus bradycardia in the setting of acute kidney injury and elevated serum lithium levels. The patient required temporary management with inotropic support and transcutaneous pacing. The patient's heart rate and hypotension improved in parallel with resolution of his acute kidney injury and elevated serum lithium level after treatment with intravenous fluids. Given the prevalence of bradycardia in both the outpatient and inpatient settings, a high index of suspicion is necessary for the prevention and identification of this clinical entity to guide appropriate management.


The effect of a 12-week combined exercise intervention program on physical performance and gait kinematics in community-dwelling elderly women.
This study aimed to determine if combined exercise intervention improves physical performance and gait joint-kinematics including the joint angle and dynamic range of motion (ROM) related to the risk of falling in community-dwelling elderly women. A 12-week combined exercise intervention program with extra emphasis on balance, muscle strength, and walking ability was designed to improve physical performance and gait. Twenty participants attended approximately two-hour exercise sessions twice weekly for 12 weeks. Participants underwent a physical performance battery, including static balance, sit and reach, whole body reaction time, 10 m obstacle walk, 10 m maximal walk, 30-second chair stand, to determine a physical performance score, and received quantitative gait kinematics measurements at baseline and in 12 weeks. Significant lower extremity strength improvement 13.5% (p<.001) was observed, which was accompanied by significant decreases in time of the 10 m obstacle walk (p<.05) and whole body reaction time (p<.001) in this study. However, no significant differences were seen for static balance and flexibility from baseline. For gait kinematics, in the mid-swing phase, knee and hip joint angle changed toward flexion (p<.01, p<.05, respectively). Ankle dynamic ROM significantly increased (p<.05) following exercise intervention. The plantar flexion angle of the ankle in the toe-off phase was increased significantly (p<.01). However, other gait parameters were not significantly different from baseline. These findings from the present investigation provide evidence of significant improvements in physical performance related to the risk factors of falling and safe gait strategy with a combined exercise intervention program in community-dwelling elderly women. The results suggest this exercise intervention could be an effective approach to ameliorate the risk factors for falls and to promote safer locomotion in elderly community-dwelling women.


Does Interest in Smoking Affect Youth Selection of Pro-smoking Videos? A Selective Exposure Experiment.
Many pro-smoking videos on YouTube reach view counts in the hundreds of thousands and more. Yet, there is limited information on who is viewing these potentially misleading videos. This study attempts to understand the viewership of online pro-smoking videos to examine if youth at high risk for smoking are more likely to watch these videos. We conducted a selective exposure experiment with a national sample of youths (ages 15-21 years; n = 614) to identify characteristics that make individuals more likely to select pro-smoking videos. During a 10-min browsing session, participants were given a set of 16 videos (eight smoking and eight nonsmoking) and were asked to view video(s) of their choice. Exposure to videos was unobtrusively logged. View count was manipulated such that smoking videos had either high or low views. Behavioral data revealed that youth with higher interest in smoking were more likely to select and spend more time watching pro-smoking videos than youth with lower interest in smoking. The view count manipulation did not affect selection patterns. However, exposure to high view count smoking videos was associated with more positive attitudes toward smoking. The findings of this study call into question the existence and prominence of pro-smoking videos on YouTube and bring to attention the need for regulatory or monitoring efforts of such content. Given the presence and prevalence of misleading pro-smoking videos online, this is the first study to ask the practical and important question of who is viewing these videos. Using behavioral data, we are able to demonstrate that youth who are high at risk for smoking are more susceptible to select and spend more time viewing pro-smoking videos than youth who are low at risk for smoking. Findings also show that when pro-smoking videos appear to be "popular," they affect attitudes toward smoking. Our findings provide policy implications regarding regulation of smoking promotion videos online.


How COVID-19 kick-started online learning in medical education-The DigiMed study.
The coronavirus disease 2019 (COVID-19) pandemic led to far-reaching restrictions of social and professional life, affecting societies all over the world. To contain the virus, medical schools had to restructure their curriculum by switching to online learning. However, only few medical schools had implemented such novel learning concepts. We aimed to evaluate students' attitudes to online learning to provide a broad scientific basis to guide future development of medical education. Overall, 3286 medical students from 12 different countries participated in this cross-sectional, web-based study investigating various aspects of online learning in medical education. On a 7-point Likert scale, participants rated the online learning situation during the pandemic at their medical schools, technical and social aspects, and the current and future role of online learning in medical education. The majority of medical schools managed the rapid switch to online learning (78%) and most students were satisfied with the quantity (67%) and quality (62%) of the courses. Online learning provided greater flexibility (84%) and led to unchanged or even higher attendance of courses (70%). Possible downsides included motivational problems (42%), insufficient possibilities for interaction with fellow students (67%) and thus the risk of social isolation (64%). The vast majority felt comfortable using the software solutions (80%). Most were convinced that medical education lags behind current capabilities regarding online learning (78%) and estimated the proportion of online learning before the pandemic at only 14%. In order to improve the current curriculum, they wish for a more balanced ratio with at least 40% of online teaching compared to on-site teaching. This study demonstrates the positive attitude of medical students towards online learning. Furthermore, it reveals a considerable discrepancy between what students demand and what the curriculum offers. Thus, the COVID-19 pandemic might be the long-awaited catalyst for a new "online era" in medical education.


Validation of noninvasive photoacoustic measurements of sagittal sinus oxyhemoglobin saturation in hypoxic neonatal piglets.
We hypothesize that noninvasive photoacoustic imaging can accurately measure cerebral venous oxyhemoglobin saturation (So2) in a neonatal model of hypoxia-ischemia. In neonatal piglets, which have a skull thickness comparable to that of human neonates, we compared the photoacoustic measurement of sagittal sinus So2 against that measured directly by blood sampling over a wide range of conditions. Systemic hypoxia was produced by decreasing inspired oxygen stepwise (i.e., 100, 21, 19, 17, 15, 14, 13, 12, 11, and 10%) with and without unilateral or bilateral ligation of the common carotid arteries to enhance hypoxia-ischemia. Transcranial photoacoustic sensing enabled us to detect changes in sagittal sinus O2 saturation throughout the tested range of 5-80% without physiologically relevant bias. Despite lower cortical perfusion and higher oxygen extraction in groups with carotid occlusion at equivalent inspired oxygen, photoacoustic measurements successfully provided a robust linear correlation that approached the line of identity with direct blood sample measurements. Receiver-operating characteristic analysis for discriminating So2 <30% showed an area under the curve of 0.84 for the pooled group data, and 0.87, 0.91, and 0.92 for hypoxia alone, hypoxia plus unilateral occlusion, and hypoxia plus bilateral occlusion subgroups, respectively. The detection precision in this critical range was confirmed with sensitivity (87.0%), specificity (86.5%), accuracy (86.8%), positive predictive value (90.5%), and negative predictive value (81.8%) in the combined dataset. These results validate the capability of photoacoustic sensing technology to accurately monitor sagittal sinus So2 noninvasively over a wide range and support its use for early detection of neonatal hypoxia-ischemia. NEW & NOTEWORTHY We present data to validate the noninvasive photoacoustic measurement of sagittal sinus oxyhemoglobin saturation. In particular, this paper demonstrates the robustness of this methodology during a wide range of hemodynamic and physiological changes induced by the stepwise decrease of fractional inspired oxygen to produce hypoxia and by unilateral and bilateral ligation of the common carotid arteries preceding hypoxia to produce hypoxia-ischemia. This technique may be useful for diagnosing risk of neonatal hypoxic-ischemic encephalopathy.


The clinical anatomy of undescended testis and varicocele for laparoscopic management.
Undescended testis or cryptorchidism remains a common condition. It affects 1% of individuals! and is treated by pediatric surgeons, urologists, and general surgeons depending on the age of the patient, spe- cialist services, and expertise available. Laparoscopy has been used for the localization of impalpable testis for more than 15years. However, minimal access surgery has now made its impact in this field of surgery in terms of surgical intervention. It is used not only for the localization of undescended testis but also to per- form Iaparosco'pic orchidectomy/ and both stages of the Foweler-Stevens orchiopexyY Minimal access surgery is also used for the ligation of the testicular vein for var-icocele.' The clinical anatomy of the unde- scended testis and varicocele is interrelated and therefore is dealt with in the same chapter, although there is no association between the two clinical conditions.


A case of standardization? Implementing health promotion guidelines in Denmark.
Guidelines are increasingly used in an effort to standardize and systematize health practices at the local level and to promote evidence-based practice. The implementation of guidelines frequently faces problems, however, and standardization processes may in general have other outcomes than the ones envisioned by the makers of standards. In 2012, the Danish National Health Authorities introduced a set of health promotion guidelines that were meant to guide the decision making and priority setting of Denmark's 98 local governments. The guidelines provided recommendations for health promotion policies and interventions and were structured according to risk factors such as alcohol, smoking and physical activity. This article examines the process of implementation of the new Danish health promotion guidelines. The article is based on qualitative interviews and participant observation, focusing on the professional practices of health promotion officers in four local governments as well as the field of Danish health promotion more generally. The analysis highlights practices and episodes related to the implementation of the guidelines and takes inspiration from Timmermans and Epstein's sociology of standards and standardization. It remains an open question whether or not the guidelines lead to more standardized policies and interventions, but we suggest that the guidelines promote a risk factor-oriented approach as the dominant frame for knowledge, reasoning, decision making and priority setting in health promotion. We describe this process as a case of epistemic standardization.


Ultrafast nonlinear optical response of a single gold nanorod near its surface plasmon resonance.
The ultrafast optical nonlinearity of an optically characterized single gold nanorod is investigated around its surface plasmon resonance, by combining a far-field spatial modulation technique with a high sensitivity pump-probe setup. The spectrally and temporally dependent response is quantitatively interpreted in terms of the bulklike optical nonlinearity enhanced by the plasmonic effect. The plasmon resonance dynamics is shown to be mostly governed by nonequilibrium electron and phonon processes. Their contributions to the nonlinear optical response of a single metal nano-object are elucidated, and the latter is connected to the nonlinearities of ensembles.


Impairment of social perception associated with lesions of the prefrontal cortex.
Behavioral and social impairments have been frequently reported after damage to the prefrontal cortex in humans. This study evaluated social perception in patients with prefrontal cortex lesions and compared their performance on a social perception task with that of healthy volunteers. Thirty-three patients with prefrontal cortex lesions and 31 healthy volunteers were tested with the Interpersonal Perception Task. In this task, subjects viewed videotaped social interactions and relied primarily on nonverbal cues to make interpersonal judgments, such as determining the degree of intimacy between two persons depicted in the videotaped scene. Patients with prefrontal cortex lesions were classified according to lesion involvement of specific regions, including the orbitofrontal cortex, dorsolateral prefrontal cortex, and anterior cingulate cortex. Relative to the comparison subjects, patients whose lesions involved the orbitofrontal cortex demonstrated impaired social perception. Contrary to predictions, patients with lesions in the dorsolateral prefrontal cortex also showed deficits in using social cues to make interpersonal judgments. All patients, particularly those with lesions in the dorsolateral prefrontal cortex, showed poorer insight into their deficits, relative to healthy volunteers. These findings of deficits in social perception after damage to the orbitofrontal cortex extend previous clinical and experimental evidence of damage-related impairment in other aspects of social cognition, such as the ability to accurately evaluate emotional facial expressions. In addition, the results suggest that the dorsolateral prefrontal cortex is recruited when inferences about social interactions are made on the basis of nonverbal information.


Positive choices: outcomes of a brief risk reduction intervention for newly HIV-diagnosed men who have sex with men.
Positive choices (PC), a brief sexual risk reduction intervention conducted with newly HIV-diagnosed men who have sex with men (MSM), was evaluated for preliminary efficacy. Participants were enrolled if they reported unprotected anal intercourse (UAI) in the three months prior to HIV diagnosis (n = 102). Three months after diagnosis, participants completed baseline assessments and were randomly assigned to receive the 3-session PC intervention or the comprehensive standard of care (C-SoC) at a community health center. Participants completed assessments at 3- (post intervention), 6-, and 9- months after baseline. Compared to C-SoC participants, PC participants significantly reduced the frequency of UAI with HIV serodiscordant (HIV negative or status unknown) partners over the 9-month follow-up period. No differences by condition were found in the frequency of UAI with all partners. The findings from this trial suggest that brief risk reduction approaches for newly-diagnosed MSM integrated into HIV care can benefit secondary HIV prevention efforts.


Near-infrared light triggers release of Paclitaxel from biodegradable microspheres: photothermal effect and enhanced antitumor activity.
Despite advances in controlled drug delivery, reliable methods for activatable, high-resolution control of drug release are needed. The hypothesis that the photothermal effect mediated by a near-infrared (NIR) laser and hollow gold nanospheres (HAuNSs) could modulate the release of anticancer agents is tested with biodegradable and biocompatible microspheres (1-15 microm) containing the antitumor drug paclitaxel (PTX) and HAuNSs (approximately 35 nm in diameter), which display surface plasmon absorbance in the NIR region. HAuNS-containing microspheres exhibit a NIR-induced thermal effect similar to that of plain HAuNSs. Rapid, repetitive PTX release from the PTX/HAuNS-containing microspheres is observed upon irradiation with NIR light (808 nm), whereas PTX release is insignificant when the NIR light is switched off. The release of PTX from the microspheres is readily controlled by the output power of the NIR laser, duration of irradiation, treatment frequency, and concentration of HAuNSs embedded inside the microspheres. In vitro, cancer cells incubated with PTX/HAuNS-loaded microspheres and irradiated with NIR light display significantly greater cytotoxic effects than cells incubated with the microspheres alone or cells irradiated with NIR light alone, owing to NIR-light-triggered drug release. Treatment of human U87 gliomas and MDA-MB-231 mammary tumor xenografts in nude mice with intratumoral injections of PTX/HAuNS-loaded microspheres followed by NIR irradiation results in significant tumor-growth delay compared to tumors treated with HAuNS-loaded microspheres (no PTX) and NIR irradiation or with PTX/HAuNS-loaded microspheres alone. The data support the feasibility of a therapeutic approach in which NIR light is used for simultaneous modulation of drug release and induction of photothermal cell killing.


Characterization of electroconvulsive seizure-induced TIMP-1 and MMP-9 in hippocampal vasculature.
Degradation of the vascular basement membrane stimulates angiogenesis and is tightly controlled by balancing the actions of metalloproteases and their inhibitors. Previous work demonstrated that electroconvulsive seizure (ECS) elevates angiogenic factors and endothelial proliferation in the hippocampus. The robust induction of tissue inhibitor of matrix metalloprotease 1 (TIMP-1) in the stratum lacunosum moleculare (SLM) corresponds to sites of increased vascular density. This led us to examine the spatial and cellular expression of TIMP-1 and its substrate, matrix metalloprotease 9 (MMP-9). Chronic ECS increased TIMP-1 by 12-fold and MMP-9 by 3-fold in discrete SLM cells. We then characterized the expression of TIMP-1 mRNA in relation to vasculature in the SLM and glial-limiting membrane (GLM). Employing laser microdissection we identified the cell types associated with SLM vasculature and also phenotyped the cells expressing TIMP-1 and MMP-9. We concluded that TIMP-1 is produced by perivascular cells positive for alpha smooth actin and that MMP-9 is expressed by GFAP-positive astrocytes. These studies suggest that ECS-induced remodelling occurs at the vascular basement membrane and facilitates neovascularization.


Individual housing induces altered immuno-endocrine responses to psychological stress in male mice.
Social isolation and lack of social support have deleterious effects on health, thus being regarded as one of the most relevant causes of diseases in human and other mammalian species. However, only few are the studies aimed at evaluating the psychoneuroimmunological functions of individually housed subjects. The present study was designed to understand how the behavior and the physiology of male house mice might be affected by individual housing. We first analyzed whether individual housing of different duration (1-42 days) would result in immuno-endocrine dysfunction (experiment 1). Then we investigated whether housing conditions would affect the reaction to an acute mild psychological stress (experiments 2 and 3). There were three main findings: first, individually housing mice for increasing time periods did not induce any major immuno-endocrine effects compared to a stable sibling group housing. Therefore, prolonged isolation does not seem to dramatically impair mice immuno-endocrine functions. Second, when exposed to a mild acute stress, i.e. forced exposure to a novel environment, isolated mice showed higher basal corticosterone and lower type 1 (IL-2) and type 2 (IL-4) cytokines as well as splenocytes proliferation compared to group housed male mice. Finally, when faced with a free choice between a novel environment and their home cage, individually housed mice showed reduced neophobic responses resulting in increased exploration of the novel environment, thus suggesting a low anxiety profile. Altogether, our findings suggest that individual housing in itself does not change immunocompetence and corticosterone level, but does affect reactivity to a stressor. In fact, individually housed mice showed high behavioral arousal, as well as altered immuno-endocrine parameters, when challenged with mild psychological novelty-stress.


Complement activation in diabetes mellitus.
To see whether or not there is complement activation in patients with diabetes mellitus, we investigated the plasma concentrations of C4, C3, C4a, C3a and SC5b-9 in either juvenile or adult onset insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetic patients at least 2 years after diagnosis. C4, C3, SC5b-9 plasma levels were not significantly different in IDDM and NIDDM patients than in age-matched controls. Anaphylatoxin peptide conversion product C4a, but not C3a, was found significantly higher in adult-onset IDDM patients than in patients with juvenile onset IDDM, NIDDM patients and age-matched controls. Complement activation did not appear to be correlated with the metabolic control, nor the duration of disease nor the presence of circulating antibodies (including islet cells (ICA), insulin (IA), thyroid microsomal (TMA), and thyroglobulin (TGA)). Although there are many factors that may trigger complement activation, we found the highest levels of C4a in elderly subjects (both diabetics and control subjects) and particularly in those who had clinically detectable vascular complications.


Respiratory and postural changes in intercostal muscle length in supine dogs.
In an attempt to assess the physiological function(s) of the external (E) and internal interosseous (I) intercostal muscles, we measured the changes in intercostal muscle length during spontaneous breathing, during passive inflation, and during passive rotation of the trunk. Studies were performed on 46 muscles from 16 supine anesthetized dogs, and changes in muscle length were assessed by sonomicrometry. The changes were small during spontaneous breathing, whether before or after bilateral phrenicotomy, and the pattern was variable among animals and among interspaces. The E, however, particularly in the lower interspaces, often lengthened with inspiration, and the I, in particular in the upper interspaces, often shortened with inspiration. Only occasionally did the E and I in one interspace change in length in opposing directions. This was also true during passive inflation, where both E and I usually shortened in the upper interspaces and lengthened in the lower interspaces. By contrast, during passive rotation of the trunk, the E and I systematically changed in length in opposing directions, and either muscle could successively lengthen and shorten a substantial amount depending on the side of rotation. These results suggest that 1) the E and I in supine dogs do not behave as antagonistic muscles during moderate respiratory efforts; and 2) they do behave as antagonistic muscles during rotation of the trunk. A primary function of these muscles as rotators of the trunk, unlike breathing, may explain why two layers of intercostal muscles with different fiber orientation exist between the ribs.


Spatio-temporal manipulation of small GTPase activity at subcellular level and on timescale of seconds in living cells.
Dynamic regulation of the Rho family of small guanosine triphosphatases (GTPases) with great spatiotemporal precision is essential for various cellular functions and events(1, 2). Their spatiotemporally dynamic nature has been revealed by visualization of their activity and localization in real time(3). In order to gain deeper understanding of their roles in diverse cellular functions at the molecular level, the next step should be perturbation of protein activities at a precise subcellular location and timing. To achieve this goal, we have developed a method for light-induced, spatio-temporally controlled activation of small GTPases by combining two techniques: (1) rapamycin-induced FKBP-FRB heterodimerization and (2) a photo-caging method of rapamycin. With the use of rapamycin-mediated FKBP-FRB heterodimerization, we have developed a method for rapidly inducible activation or inactivation of small GTPases including Rac(4), Cdc42(4), RhoA(4) and Ras(5), in which rapamycin induces translocation of FKBP-fused GTPases, or their activators, to the plasma membrane where FRB is anchored. For coupling with this heterodimerization system, we have also developed a photo-caging system of rapamycin analogs. A photo-caged compound is a small molecule whose activity is suppressed with a photocleavable protecting group known as a caging group. To suppress heterodimerization activity completely, we designed a caged rapamycin that is tethered to a macromolecule such that the resulting large complex cannot cross the plasma membrane, leading to virtually no background activity as a chemical dimerizer inside cells(6). Figure 1 illustrates a scheme of our system. With the combination of these two systems, we locally recruited a Rac activator to the plasma membrane on a timescale of seconds and achieved light-induced Rac activation at the subcellular level(6).


Nosocomial candiduria in chronic liver disease patients at a hepatobilliary center.
Nosocomial urinary tract infections (UTIs) are common in catheterized patients. Fungal UTI has become an important nosocomial problem over the past decade. The microbiology of candiduria is rapidly evolving and new trends are being reported. To study the microbiological trends and antifungal resistance profile of Candida in urine of catheterized chronic liver disease (CLD) patients at a super specialty hepatobiliary tertiary-care center. urine samples were collected by sterile technique, processed by semi-quantitative method as per the standard protocols. Direct microscopic examination of urine sample was also done to look for the presence of pus cells, red blood cells, casts, crystals or any bacterial or fungal element. A total of 337 yeast isolates were obtained from catheterized patients, non-albicans Candida spp. emerged as the predominant pathogen and was responsible for 67.06% of nosocomial fungal UTI. Candida tropicalis accounted for 34.71% of the cases, whereas Candida albicans grew in 32.93%, Candida glabrata 16.32%, rare Candida spp. Nearly 11.5% (Candida hemolunii to be confirmed by molecular methods). Antifungal sensitivity varied non-albicans species except C. tropicalis, Candida parapsilosis were more often resistant to antifungal drugs. Nosocomial Candida UTIs in CLD patients is common, due to the cumulative pressure of contributing factors such as urinary instrumentation and prolonged use of broad-spectrum antibiotics. Non-albicans Candida were found to outnumber C. albicans in catherized CLD patients. Risk of strain persistence is also higher with non-albicans Candida. Thus, species identification and susceptibility testing is a must for appropriate management of such patients.


Targeting of VX2 rabbit liver tumor by selective delivery of 3-bromopyruvate: a biodistribution and survival study.
The aim of this study was to determine the biodistribution and tumor targeting ability of (14)C-labeled 3-bromopyruvate ([(14)C]3-BrPA) after i.a. and i.v. delivery in the VX2 rabbit model. In addition, we evaluated the effects of [(14)C]3-BrPA on tumor and healthy tissue glucose metabolism by determining (18)F-deoxyglucose (FDG) uptake. Last, we determined the survival benefit of i.a. administered 3-BrPA. In total, 60 rabbits with VX2 liver tumor received either 1.75 mM [(14)C]3-BrPA i.a., 1.75 mM [(14)C]3-BrPA i.v., 20 mM [(14)C]3-BrPA i.v., or 25 ml of phosphate-buffered saline (PBS). All rabbits (with the exception of the 20 mM i.v. group) received FDG 1 h before sacrifice. Next, we compared survival of animals treated with i.a. administered 1.75 mM [(14)C]3-BrPA in 25 ml of PBS (n = 22) with controls (n = 10). After i.a. infusion, tumor uptake of [(14)C]3-BrPA was 1.8 +/- 0.2% percentage of injected dose per gram of tissue (%ID/g), whereas other tissues showed minimal uptake. After i.v. infusion (1.75 mM), tumor uptake of [(14)C]3-BrPA was 0.03 +/- 0.01% ID/g. After i.a. administration of [(14)C]3-BrPA, tumor uptake of FDG was 26 times lower than in controls. After i.v. administration of [(14)C]3-BrPA, there was no significant difference in tumor FDG uptake. Survival analysis showed that rabbits treated with 1.75 mM 3-BrPA survived longer (55 days) than controls (18.6 days). Intra-arterially delivered 3-BrPA has a favorable biodistribution profile, combining a high tumor uptake resulting in blockage of FDG uptake with no effects on healthy tissue. The local control of the liver tumor by 3-BrPA resulted in a significant survival benefit.


Associations between free sugars and nutrient intakes among children and adolescents in the UK.
This study explored associations between free sugars intake (using non-milk extrinsic sugars as proxy) and nutrient intakes among children aged 1·5-18 years in the UK National Diet and Nutrition Survey 2008-2012. Dietary records were completed by 2073 children (95 % completed 4 d). Mean free sugars intakes (% energy) were 11·8, 14·7 and 15·4 % in the 1·5-3, 4-10 and 11-18 years age groups, respectively. Nutrient intakes and nutrient density were compared across quintiles (Q1-Q5) of free sugars intake (% energy) within each age group. Energy intake rose from Q1 to Q5 of free sugars, whereas percentages of energy intake from fat, SFA and protein dropped. Associations with micronutrients (mg/d or mcg/d) were mostly non-significant, but among 11-18-year-olds there were significant negative associations with Zn, Se, Fe, Cu, and vitamin A and D. There were stronger negative associations with micronutrient density (mg/mcg per 4·18 MJ) for most nutrients in all age groups. Associations with vitamin C were positive. Results were similar after excluding misreporters. Children aged 4-18 years who consumed average amounts of free sugars or above (>13 % energy or Q3-Q5) had lower diet quality than those consuming <10 % free sugars (Q1), but there were insufficient data to assess diets with 5 % free sugars. High consumers obtained a higher proportion of free sugars from soft drinks, fruit juice and sugar confectionery and less from breakfast cereals. Ultimately, nutrient intakes depend on the total dietary pattern; however, reducing overconsumption of sugary foods and drinks with low nutrient density may help improve diet quality.


Iron phthalocyanine-derived nanozyme as dual reactive oxygen species generation accelerator for photothermally enhanced tumor catalytic therapy.
Nanozymes are artificial enzymes that mimic natural enzyme-like activities and show great promise for tumor catalytic therapy. However, new nanozymes with multiple catalytic activities for multifunctional nanotheranostic use remain challenging to design. Herein, for the first time, iron phthalocyanine (Fe(II)Pc) was assembled with poly(l-lactide-co-glycolide)-block-poly(ethylene glycol) to prepare an Fe(II)Pc assembly (denoted as Fe(II)Pc-A). The obtained Fe(II)Pc-A could be applied as a smart near-infrared (NIR) light-responsive nanotheranostic for simultaneous photoacoustic imaging-guided photothermal therapy. Notably, Fe(II)Pc-A possessed peroxidase, catalase, and oxidase mimicking activities, which could not only catalyze the conversion of intratumoral H2O2 to •OH, but also degrade H2O2 to generate O2 and continuously catalyze the conversion of O2 to cytotoxic O2•-. Impressively, the dual reactive oxygen species (ROS) generation of Fe(II)Pc-A was further remarkably enhanced by the endogenous acidity of the tumor microenvironment and the exogenous NIR light-responsive photothermal effect. Moreover, the O2 self-supplying ability of Fe(II)Pc-A led to increased generation of O2•- for enhancing catalytic therapy in hypoxic tumor. These collective properties of Fe(II)Pc-A nanozyme enabled it to be a dual ROS generation accelerator for photothermally enhanced tumor catalytic therapy. Thus, a new type of high-performance nanozyme for multifunctional nanotheranostic use toward cancer was presented.


Biochemical impedance on intracellular functions of vitamin B12 in chronic toxigenic mold exposures.
A majority of patients with neurological disorders with chronic exposures to toxigenic molds and mycotoxins has vitamin B12 deficiency that is unrelated to dietary insufficiency. Vitamin B12 is a source of coenzymes, and participates in intracellular recycling of methionine, and in methionine synthase reactions. The biochemical processes that lead to B12 depletion and deficiency are not fully understood. This paper examines and assesses various most likely biochemical reasons that could impede upon the normal intracellular functions of vitamin B12 that lead to neurological manifestations. By biochemical implications and derivations, it is most likely that mycotoxins interrupt the structure and function of vitamin B12 through reactive interference with the normal One-Carbon metabolism leading to the observed clinical neurological manifestations such as nerve damage and, demyelination, degeneration of PNS leading to paralysis, progressive peripheral neuropathy, and spinal degeneration.


3' RACE walking along a large cDNA employing tiered suppression PCR.
Large genes present particular cloning difficulties, especially when expressed at relatively low levels. We describe a novel method, termed 3' rapid amplification of cDNA ends (RACE) walking, for the rapid determination of unknown 3' flanking sequence of a large cDNA. The technique is a derivative of the anchored PCR 5' RACE procedure but includes a specific and limited second-strand cDNA synthesis and a tiered "panhandle" suppression of nonspecific products. The method generated 900 bp of new sequence for the large tammar wallaby ATRY gene in two easy steps, in which standard 3' RACE and PCR-based cDNA library walking proved unsuccessful. This robust approach represents a new tool for isolating unknown sequence under challenging cloning scenarios such as poor library representation, long coding regions, long 3' untranslated regions, and difficult template regions.


Health and nutrition economics: diet costs are associated with diet quality.
The WHO asserts that the global food price crisis threatens public health and jeopardizes the health of the most disadvantaged groups such as women, children, the elderly and low-income families. Economic factors play a crucial role and could affect personal nutrition status and health. Economic decision factors such as food price and income do influence people's food choices. Moreover, food costs are a barrier for low income-families to healthier food choices. Several studies indicate that diet costs are associated with dietary quality and also food safety. Food prices have surged over the past couple of years (2007-9) and raised serious concerns about food security around the world. Rising food prices are having severe impacts on population health and nutritional status. Therefore, people who change their diet pattern for economic reasons may develop a range of nutritionally-related disorders and diseases, from so-called over-nutrition to or with under-nutrition even within the one household. This is likely to increase with growing food insecurity. Presently, economics is not integrated with mainstream nutrition science or practice, other than in "home economics", but it can enable greater understanding of how socioeconomic status may interplay with human nutritional status and health and how these situations might be resolved. Collaborative, cross-disciplinary nutritional economics research should play a greater role in the prevention and management of food crises.


Drosophila TCTP is essential for growth and proliferation through regulation of dRheb GTPase.
Cellular growth and proliferation are coordinated during organogenesis. Misregulation of these processes leads to pathological conditions such as cancer. Tuberous sclerosis (TSC) is a benign tumour syndrome caused by mutations in either TSC1 or TSC2 tumour suppressor genes. Studies in Drosophila and other organisms have identified TSC signalling as a conserved pathway for growth control. Activation of the TSC pathway is mediated by Rheb (Ras homologue enriched in brain), a Ras superfamily GTPase. Rheb is a direct target of TSC2 and is negatively regulated by its GTPase-activating protein activity. However, molecules required for positive regulation of Rheb have not been identified. Here we show that a conserved protein, translationally controlled tumour protein (TCTP), is an essential new component of the TSC-Rheb pathway. Reducing Drosophila TCTP (dTCTP) levels reduces cell size, cell number and organ size, which mimics Drosophila Rheb (dRheb) mutant phenotypes. dTCTP is genetically epistatic to Tsc1 and dRheb, but acts upstream of dS6k, a downstream target of dRheb. dTCTP directly associates with dRheb and displays guanine nucleotide exchange activity with it in vivo and in vitro. Human TCTP (hTCTP) shows similar biochemical properties compared to dTCTP and can rescue dTCTP mutant phenotypes, suggesting that the function of TCTP in the TSC pathway is evolutionarily conserved. Our studies identify TCTP as a direct regulator of Rheb and a potential therapeutic target for TSC disease.


Four outbreaks of human trichinellosis in Henan Province.
Four outbreaks of human trichinellosis caused by eating pork together had occurred successively in two rural areas and two cities of Henan Province, where the disease is endemic. Of the 110 persons involved, 54 had the onset. All of them had the history of eating pork. In the outbreak of Dengzhou, in those persons who dined together, men were all uninfected and 13 women were infected. The difference found between sexes was suggested to be related with spirit drinking. In these 54 patients, the latent period ranged from 3 to 28 days. The relevant clinical symptoms and signs were fever, edema, myalgia, rash, headache, nausea, abdominal pain and diarrhea. Vomiting was uncommon. Most patients were hospitalized and all cases recovered in two weeks after proper treatment with albendazole.


Effects of beta-endorphin on norepinephrine release in hypertension.
Recent studies have suggested an involvement of the endogenous opioid system in blood pressure control. The purpose of the present study was to determine the role of beta-endorphin in the regulation of sympathetic nervous activity in the central nervous system of hypertension. The effects of beta-endorphin on the electrically evoked release of [3H]norepinephrine (NE) were investigated in superfused slices of rat medulla oblongata. Beta-endorphin inhibited the stimulation-evoked NE release in a dose-dependent manner in rat medulla oblongata. In the medulla oblongata of spontaneously hypertensive rats (SHR), the inhibitory effect of beta-endorphin on the stimulation-evoked NE release was significantly smaller than in the medulla oblongata of Wistar-Kyoto rats. These results showed that beta-endorphin might reduce NE release in rat medulla oblongata. Furthermore, the lesser inhibitory effect of beta-endorphin on NE release in SHR might suggest that the opioid peptide could be involved in the regulation of central sympathetic nervous activity in hypertension.


Discovery of a Thermostable GH10 Xylanase with Broad Substrate Specificity from the Arctic Mid-Ocean Ridge Vent System.
A two-domain GH10 xylanase-encoding gene (amor_gh10a) was discovered from a metagenomic data set, generated after in situ incubation of a lignocellulosic substrate in hot sediments on the sea floor of the Arctic Mid-Ocean Ridge (AMOR). AMOR_GH10A comprises a signal peptide, a carbohydrate-binding module belonging to a previously uncharacterized family, and a catalytic glycosyl hydrolase (GH10) domain. The enzyme shares the highest sequence identity (42%) with a hypothetical protein from a Verrucomicrobia bacterium, and its GH10 domain shares low identity (24 to 28%) with functionally characterized xylanases. Purified AMOR_GH10A showed thermophilic and halophilic properties and was active toward various xylans. Uniquely, the enzyme showed high activity toward amorphous cellulose, glucomannan, and xyloglucan and was more active toward cellopentaose than toward xylopentaose. Binding assays showed that the N-terminal domain of this broad-specificity GH10 binds strongly to amorphous cellulose, as well as to microcrystalline cellulose, birchwood glucuronoxylan, barley β-glucan, and konjac glucomannan, confirming its classification as a novel CBM (CBM85).IMPORTANCE Hot springs at the sea bottom harbor unique biodiversity and are a promising source of enzymes with interesting properties. We describe the functional characterization of a thermophilic and halophilic multidomain xylanase originating from the Arctic Mid-Ocean Ridge vent system, belonging to the well-studied family 10 of glycosyl hydrolases (GH10). This xylanase, AMOR_GH10A, has a surprisingly wide substrate range and is more active toward cellopentaose than toward xylopentaose. This substrate promiscuity is unique for the GH10 family and could prove useful in industrial applications. Emphasizing the versatility of AMOR_GH10A, its N-terminal domain binds to both xylans and glycans, while not showing significant sequence similarities to any known carbohydrate-binding module (CBM) in the CAZy database. Thus, this N-terminal domain lays the foundation for the new CBM85 family.


Methods for assessing responsiveness: a critical review and recommendations.
A review of the literature suggests there are two major aspects of responsiveness. We define the first as "internal responsiveness," which characterizes the ability of a measure to change over a prespecified time frame, and the second as "external responsiveness, " which reflects the extent to which change in a measure relates to corresponding change in a reference measure of clinical or health status. The properties and interpretation of commonly used internal and external responsiveness statistics are examined. It is from the interpretation point of view that external responsiveness statistics are considered particularly attractive. The usefulness of regression models for assessing external responsiveness is also highlighted.


[Cutaneous reactions due to the use of epidermal growth factor receptor inhibitors: two case reports].
An increase in the expression of epidermal growth factor receptors (EGFR) is involved in the stimulation of tumor development. EGFR inhibitors have shown efficacy in the treatment of neoplasms of the head, neck, colon and lung. EGFR when inhibited can cause cutaneous reactions in more than 50% of the patients. They are usually reversible, but when severe, limit the use of the drug. Papulopustulars lesions in the face and upper torso are the most common, as well as xerosis, hair and nail changes. There is a direct relationship between the degree of cutaneous toxicity and the antitumoral response. An adequate dermatologic approach is necessary for an effective therapy against cancer.


Mitogen-activated protein kinase dynamics during the meiotic G2/MI transition of mouse spermatocytes.
Cellular and genetic approaches were used to investigate the requirements for activation during spermatogenesis of the extracellular signal-regulated protein kinases (ERKs), more commonly known as the mitogen-activated protein kinases (MAPKs). The MAPKS and their activating kinases, the MEKs, are expressed in specific developmental patterns. The MAPKs and MEK2 are expressed in all premeiotic germ cells and spermatocytes, while MEK1 is not expressed abundantly in pachytene spermatocytes. Phosphorylated (active) variants of these kinases are diminished in pachytene spermatocytes. Treatment of pachytene spermatocytes with okadaic acid (OA), to induce transition from meiotic prophase to metaphase I (G2/MI), resulted in phosphorylation and enzymatic activation of ERK1/2. However, U0126, an inhibitor of the ERK-activating kinases, MEK1/2, did not inhibit OA-induced MAPK activation or chromosome condensation. Analysis of spermatocytes lacking MOS, a mitogen-activated protein kinase kinase kinase responsible for MEK and MAPK activation, revealed that MOS is not required for OA-induced activation of the MAPKs. OA-induced MAPK activation was inhibited by butyrolactone I, an inhibitor of cyclin-dependent kinases 1 and 2 (CDK1, CDK2); thus, these kinases may regulate MAPK activity. Additionally, spermatocytes lacking CDC25C condensed bivalent chromosomes and activated both MPF and MAPKs in response to OA treatment; therefore, there is a CDC25C-independent pathway for MPF and MAPK activation. These studies reveal that spermatocytes do not require either MOS or CDC25C for onset of the meiotic division phase or for activation of MPF and the MAPKs, thus implicating a novel pathway for activation of the ERK1/2 MAPKs in spermatocytes.


Single-stranded DNA viruses employ a variety of mechanisms for integration into host genomes.
Single-stranded DNA (ssDNA) viruses are widespread in the environment and include economically, medically, and ecologically important pathogens. Recently, it has been discovered that ssDNA virus genomes are also prevalent in the chromosomes of their bacterial, archaeal, and eukaryotic hosts. Sequences originating from viruses of the families Parvoviridae, Circoviridae, and Geminiviridae are particularly widespread in the genomes of eukaryotes, where they are often fossilized as endogenous viral elements. ssDNA viruses have evolved diverse mechanisms to invade cellular genomes, and these principally vary between viruses infecting bacteria/archaea and eukaryotes. Filamentous bacteriophages (Inoviridae) use at least three major mechanisms of integration. Some of these phages encode integrases of serine or tyrosine recombinase superfamilies, while others utilize DDE transposases of the IS3, IS30, or IS110/IS492 families, whereas some inoviruses, and possibly certain members of the Microviridae, hijack the host XerCD recombination machinery. By contrast, eukaryotic viruses for integration rely on the endonuclease activity of their rolling-circle replication-initiation proteins, mimicking the mechanisms used by some bacterial transposons. Certain bacterial and eukaryotic ssDNA viruses have embraced a transposon-like means of propagation, with occasionally dramatic effects on host genome evolution. Here, we review the diversity of experimentally verified and hypothetical mechanisms of genome integration employed by ssDNA viruses, and consider the evolutionary implications of these processes, particularly in the emergence of novel virus groups.


Acute kidney injury during leukocyte engraftment after autologous stem cell transplantation in patients with light-chain amyloidosis.
Engraftment syndrome (ES) is a complication of hematopoietic stem cell transplantation characterized by fever, rash, and non-cardiogenic pulmonary edema. Acute kidney injury (AKI) has been recognized but is considered a minor criterion in one and excluded another definition of ES. We have noted a high incidence of AKI in patients with immunoglobulin light-chain amyloidosis (AL) undergoing autologous stem cell transplant (ASCT) around the time of leukocyte engraftment. This study was conducted to further investigate the relationship between AKI and ES. Data were collected from 377 AL patients who underwent ASCT from 7/1997 to 10/2009. Patients who experienced an elevation of serum creatinine >0.5 mg/dL within 4 days of leukocyte engraftment and anyone who presented with signs associated with ES regardless of renal manifestations were included. Forty-one patients met criteria. Twelve were excluded for positive cultures (10), acute interstitial nephritis (1), and acute cellular rejection (1). In addition to AKI (93.1%), patients also exhibit fever (82.7%), hypotension (51.7%), rash (48.2%), edema (93.1%), diarrhea (69.0%), conjunctival hemorrhage (31.0%), pulmonary edema (31.0%), pulmonary hemorrhage (13.8%), and transient encephalopathy (17.2%). Patient with pulmonary involvement were more likely to require dialysis but was not statistically significant. AKI was very common during leukocyte engraftment in AL patients. While infectious etiology accounted for some of the AKI, most appeared to be associated with ES. After infection is ruled out, ES should be considered in the differential diagnosis when evaluating AKI in this population.


Duchenne muscular dystrophy: studies of cell motility in vitro.
Duchenne muscular dystrophy (DMD) is a severe degenerative disorder of skeletal muscle. It has been suggested that an abnormality of the plasma membrane may be responsible for the pathogenesis of DMD, and a number of cell surface changes have been described in DMD muscle fibres and other cell types. Alterations in cell-to-cell and cell-to-substratum adhesiveness have been reported for DMD cells and we have determined whether these alterations in cell adhesiveness affect migration of cells from DMD muscle explants. DMD cells move more rapidly and spend less time at rest than do normal or DMD carrier cells, although the differences were statistically significant only for the latter cells. An inverse relationship between cell speed and contact with surrounding cells was not observed. All cells tended to persist in their direction of movement, and there were no differences between the types of cells studied. Our results support the view that there may be a cell surface defect in DMD.


Automated description of colours in polarized-light surface microscopy images of melanocytic lesions.
The aim of this study was to develop a computerized method for the identification and description of colour areas in melanocytic lesion images based on an approach mimicking the human perception of colours. A colour palette comprising six colour groups (black, dark brown, light brown, blue-grey, red and white) was created by selecting single colour components within melanocytic lesion images acquired using a digital videomicroscope, and was implemented in the image analysis program. For each colour region, the area, the distance from the lesion centroid, the spread, the colour area distribution in the internal and the external part of the lesion, and asymmetries were assessed on 604 melanocytic lesion images in our image database. Black, white and blue-grey colour areas were detected more frequently in melanomas compared with naevi. Moreover, significant differences in colour descriptors were observed for each colour group, showing that colour areas are more unevenly distributed in melanomas compared with naevi. Using a discriminant analysis approach, the extension of dark, white and blue-grey areas and some descriptors of the distribution of the colour areas were identified as the most relevant colour parameters for differentiating between benign and malignant lesions. In conclusion, our automatic procedure breaks down the image into the colour areas used in the clinical examination process, and also supplies a description of their extension and distribution, with parameters that correlate with the clinical concepts of regularity and homogeneity.


Glutathione reductase turned into trypanothione reductase: structural analysis of an engineered change in substrate specificity.
Trypanosoma and Leishmania, pathogens responsible for diseases such as African sleeping sickness, Chagas' heart disease, or Oriental sore, are two of the very few genera that do not use the ubiquitous glutathione/glutathione reductase system to keep a stable cellular redox balance. Instead, they rely on trypanothione and trypanothione reductase to protect them from oxidative stress. Trypanothione reductase (TR) and the corresponding host enzyme, human red blood cell glutathione reductase (GR), belong to the same flavoprotein family. Despite their closely related three-dimensional structures and although their natural substrates share the common structural glutathione core, the two enzymes are mutually exclusive with respect to their disulfide substrates. This makes the parasite enzyme a potential target for antitrypanosomal drug design. While a large body of structural data on GR complexes is available, information on TR-ligand interactions is very limited. When the two amino acid changes Ala34Glu and Arg37Trp are introduced into human GR, the resulting mutant enzyme (GRTR) prefers trypanothione 700-fold over its original substrate, effectively converting a GR into a TR [Bradley, M., Bücheler, U. S., & Walsh, C. T. (1991) Biochemistry 30, 6124-6127]. The crystal structure of GRTR has been determined at 2.3 A resolution and refined to a crystallographic R factor of 20.9%. We have taken advantage of the ease with which ligand complexes can be produced in GR crystals, a property that extends to the isomorphous GRTR crystals, and have produced and analyzed crystals of GRTR complexes with glutathione, trypanothione, glutathionylspermidine and of a true catalytic intermediate, the mixed disulfide between trypanothione and the enzyme. The corresponding molecular structures have been characterized at resolutions between 2.3 and 2.8 A with R factors ranging from 17.1 to 19.7%. The results indicate that the Ala34Glu mutation causes steric hindrance leading to a large displacement of the side chain of Arg347. This movement combined with the change in charge introduced by the mutations modifies the binding cavity, forcing glutathione to adopt a nonproductive binding mode and permitting trypanothione and to a certain degree also the weak substrate glutathionylspermidine to assume a productive mode.


Epitope mapping of the Mycobacterium bovis secretory protein MPB70 using overlapping peptide analysis.
The gene encoding the major Mycobacterium bovis secreted protein MPB70 was cloned and isolated from a DNA library in lambda EMBL 3, and the restriction map of the area of chromosome containing the gene ascertained. After sub-cloning, the complete DNA sequence and predicted amino acid sequence were determined, and from this information a series of overlapping octapeptides encoding all possible linear epitopes of eight or less amino acids were synthesized. These peptides were probed with monoclonal antibodies specific for M. bovis and with sera from M. bovis-infected cattle. Epitopes defined by this technique were then examined using a substitution analysis that allowed the significance of each amino acid in the putative epitope to be quantified, and the exact specificity of the antibody response for the epitope determined.


Agonist of the adenosine A3 receptor, IB-MECA, and inhibitor of cyclooxygenase-2, meloxicam, given alone or in a combination early after total body irradiation enhance survival of γ-irradiated mice.
There exists a requirement for drugs which would be useful in therapy of an acute radiation damage of a mammalian organism. The aim of the study was to evaluate survival parameters in mice exposed to a lethal γ-ray dose of 8.5 Gy and treated with single doses of an adenosine A(3) receptor agonist, IB-MECA, or a cyclooxygenase-2 (COX-2) inhibitor, meloxicam, administered alone or in a combination early after irradiation, i.e., 0.5 and 1 h post-irradiation, respectively. The assessed parameters were the mean survival time (MST) and the cumulative percentage 30-day survival (CPS). Administrations of single intraperitoneal doses of either IB-MECA 0.5 h post-irradiation or meloxicam 1 h post-irradiation resulted in statistically significant increases of MST in comparison with the control irradiated mice. Combined administration of IB-MECA and meloxicam was found to be the only treatment statistically enhancing the parameter of CPS and to lead to the most expressive increase in MST of the experimental mice. The findings add new knowledge on the action of an adenosine A3 receptor agonist and a COX-2 inhibitor in an irradiated mammalian organism and suggest the potential of both the investigated drugs in the treatment of the acute radiation damage.


Enhanced antiretroviral therapy in rhesus macaques improves RT-SHIV viral decay kinetics.
Using an established nonhuman primate model, rhesus macaques were infected intravenously with a chimeric simian immunodeficiency virus (SIV) consisting of SIVmac239 with the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase from clone HXBc2 (RT-SHIV). The impacts of two enhanced (four- and five-drug) highly active antiretroviral therapies (HAART) on early viral decay and rebound were determined. The four-drug combination consisted of an integrase inhibitor, L-870-812 (L-812), together with a three-drug regimen comprising emtricitabine [(-)-FTC], tenofovir (TFV), and efavirenz (EFV). The five-drug combination consisted of one analog for each of the four DNA precursors {using TFV, (-)-FTC, (-)-β-D-(2R,4R)-1,3-dioxolane-2,6-diaminopurine (amdoxovir [DAPD]), and zidovudine (AZT)}, together with EFV. A cohort treated with a three-drug combination of (-)-FTC, TFV, and EFV served as treated controls. Daily administration of a three-, four-, or five-drug combination of antiretroviral agents was initiated at week 6 or 8 after inoculation and continued up to week 50, followed by a rebound period. Plasma samples were collected routinely, and drug levels were monitored using liquid chromatography-tandem mass spectrometry (LC-MS-MS). Viral loads were monitored with a standard TaqMan quantitative reverse transcriptase PCR (qRT-PCR) assay. Comprehensive analyses of replication dynamics were performed. RT-SHIV infection in rhesus macaques produced typical viral infection kinetics, with untreated controls establishing persistent viral loads of >10(4) copies of RNA/ml. RT-SHIV loads at the start of treatment (V0) were similar in all treated cohorts (P > 0.5). All antiretroviral drug levels were measureable in plasma. The four-drug and five-drug combination regimens (enhanced HAART) improved suppression of the viral load (within 1 week; P < 0.01) and had overall greater potency (P < 0.02) than the three-drug regimen (HAART). Moreover, rebound viremia occurred rapidly following cessation of any treatment. The enhanced HAART (four- or five-drug combination) showed significant improvement in viral suppression compared to the three-drug combination, but no combination was sufficient to eliminate viral reservoirs.


Site-selective probe for investigating the asynchronous unfolding of domains in bovine serum albumin.
A convenient method is proposed for precise investigation of the asynchronous structural transition of the domains in bovine serum albumin (BSA) during unfolding process. The method is based on a site-selective probe, alizarin red S (ARS), which has a high affinity to the subdomain IIA of BSA. BSA-ARS complex was formed and gradually unfolded by urea from 0 to 8.0M. The unfolding occurred in different domains of BSA resulted in distinct alterations of the microenvironment of the bound ARS. The spectral response of BSA-ARS complex, including the color, the UV absorption at 530 and 432 nm, and the intrinsic fluorescence at 342 and 310 nm with the excitation wavelength of 280 nm, showed slight changes in the urea concentration from 0 to 4.5M, drastic changes from 4.5 to 6.0M, and almost no changes from 6.0 to 8.0M. The redox behavior of bound ARS between 0.3 and 0.8 V also showed the same trend. Consequently, a two-step, three-state transition process was monitored by naked eyes, UV-vis spectroscopy and electrochemistry. It is the first report to realize the indicator of the intermediate state during the unfolding process of BSA through convenient methods instead of expensive approaches. The work provides a facile method for the investigation of the unfolding process of multidomain proteins.


A district stroke service.
Stroke is the third most common cause of death in Britain, but despite its medical and economic importance, management of the three facets of stroke--prevention, acute care and rehabilitation--has been unstructured and poor value for money. This article considers how these issues might be more effectively addressed by a pragmatic coordinated approach to the whole problem of stroke in a health authority.


Recent advances in the transesterification of β-keto esters.
The ability to selectively transesterify β-keto esters is a useful transformation in organic synthesis. The increasing interest in transesterification for the synthesis of compounds of pharmaceutical importance, as well as for biodiesel production, has led to the development of a variety of different approaches. This article aims to summarise recent advances in the transesterifications of β-keto esters. Particular interest has been paid to methodologies with minimal environmental impact.


Improved metabolic control in insulin-dependent diabetes mellitus with insulin and tolazamide.
The influence of sulfonylurea drugs in enhancing the effect of endogenous insulin is well documented. Furthermore, combination therapy with sulfonylurea and insulin is effective in the treatment of type II diabetes mellitus. Therefore, to assess the efficacy of this type of combination therapy in type I diabetes, we conducted a double-blind clinical trial with tolazamide and insulin in 15 subjects with type I diabetes. The diagnosis of type I diabetes was confirmed by previous episodes of diabetic ketoacidosis and undetectable C-peptide levels in serum samples from blood drawn from patients two hours after breakfast. During the study protocol, placebo or tolazamide was randomly added to insulin and the combination therapy was continued for three months. In the placebo group, levels of fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) did not alter significantly at the end of the study period. However, in the tolazamide group, levels of FPG and HbA1c markedly improved after administration of tolazamide (FPG levels before therapy, 10.8 +/- 0.9 mmol/L [mean +/- SEM]; after therapy, 6.7 +/- 0.4 mmol/L; HbA1c levels before therapy, 10.9% +/- 0.6%; after therapy, 9.6% +/- 0.5%). Therefore, adjuvant therapy with tolazamide and insulin may be beneficial in achieving adequate metabolic control in type I diabetes mellitus.


Natural orifice transluminal endoscopic surgery for intra-abdominal emergency conditions.
Patient benefits from natural orifice transluminal endoscopic surgery (NOTES) are of interest in acute-care surgery. This review provides an overview of the historical development of NOTES procedures, and addresses their current uses and limitations for intra-abdominal emergency conditions. A PubMed search was carried out for articles describing NOTES approaches for appendicectomy, percutaneous gastrostomy, hollow viscus perforation and pancreatic necrosectomy. Pertinent articles were reviewed and data on available outcomes synthesized. Emergency conditions in surgery tax the patient's cardiovascular and respiratory systems, and fluid and electrolyte balance. The operative intervention itself leads to an inflammatory response and blood loss, thus adding to the physiological stress. NOTES provides a minimally invasive alternative access to the peritoneal cavity, avoiding abdominal wall incisions. A clear advantage to the patient is evident with the implementation of an endoscopic approach to deal with inadvertently displaced percutaneous endoscopic gastrostomy tubes and perforated gastroduodenal ulcer. The NOTES approach appears less invasive for patients with infected pancreatic necrosis, in whom it allows surgical debridement and avoidance of open necrosectomy. Transvaginal appendicectomy is the second most frequently performed NOTES procedure after cholecystectomy. The NOTES concept has provided a change in perspective for intramural and transmural endoscopic approaches to iatrogenic perforations during endoscopy. NOTES approaches have been implemented in clinical practice over the past decade. Selected techniques offer reduced invasiveness for patients with intra-abdominal emergencies, and may improve outcomes. Steady future development and adoption of NOTES are likely to follow as technology improves and surgeons become comfortable with the approaches.


A homosexual Japanese man with acute hepatitis due to hepatitis B virus genotype ae, concurrent with amebic colitis.
We report herein a case with acute hepatitis due to hepatitis B virus genotype Ae, concurrent with amebic colitis. A 39-year-old homosexual Japanese man was admitted to our hospital with jaundice. Laboratory tests showed an elevation of transaminase and positivity for hepatitis B surface antigen and IgM-type antibody to hepatitis B core antigen. The hepatitis B virus genotype was determined to be Ae. Furthermore, a mud-like stool with blood and mucous had sometimes been noted during the past 3 years, and amebic colitis was shown by colonofiberscopy during hospitalization. The patient was diagnosed with acute hepatitis B, concurrent with amebic colitis, and was successfully treated with lamivudine and metronidazole. In Japanese patients with acute hepatitis B virus genotype A infection, homosexual activity tends to be high. Furthermore, in Japanese homosexual men, amebiasis has been increasing. Thus, in Japanese patients with acute hepatitis B, a determination of genotype should be performed in order to investigate the route of transmission of hepatitis B virus, and a search for amebiasis should be performed in patients with acute hepatitis due to hepatitis B virus genotype A. Furthermore, education of homosexual men regarding hepatitis B virus, hepatitis B virus vaccination, and amebiasis is urgently required.


[Chronic recurrent multifocal osteomyelitis].
The aim of this paper is to give a detailed description of the so-called "chronic recurrent multifocal osteomyelitis" (CRMO). The clinical, radiological and histopathological results of an analysis of 29 cases (15 children/adolescents and 14 adults) are presented and correlated to current data from the literature. We could delinate the following points: 1. CRMO is a systemic aseptic inflammation of the bone marrow (Osteitis), it can occur polytopically and association with pustulous dermatologic symptoms is possible. 2. It is not a rare disease 3. Osteomyelitis is probably "reactive" and a plasma-cell sclerotic process with ist own characteristic histologic three-phase course. 4. We could observe 5 specific types of localization which can be documented by X-ray or bone scan. 5. Accompanying arthritis os often present, especially "sympathetic coxitis". 6. The use of drugs in treatment of CRMO (i.e. azithromycin, calcitonin, and bisphosphonates) is discussed. In conclusion we want to point out, that 1. 99mTC bone scan should always be performed when there is suspicion for CRMO to reveal the pattern of affection, 2. the rheumatologist and dermatologist should be contacted, 3. operation is normally not necessary for treatment of the mostly self-limitin disease, and 4. the term "SAPHO syndrome" should be avoided, further differentiation of the diagnosis is necessary.


[Lepto-dipstick: results of its application to the fast diagnosis of human leptospirosis].
Forty one serum specimens from critical patients who were suspected of having human leptospirosis were studied by using simultaneously convencional test Lepto-dipstick and serogroup microagglutination test (MAT) with live antigens. Different reactivity levels were reached in 26 tested samples by Lepto-dipstick. This assay and MAT coincided in 85,4% of results. It was confirmed that Lepto-dipstick detects antibodies to various leptospiral serovars and that the degree of intensity of the band staining corresponded with the level of detected antibodies by MAT. The implementation of Lepto-dipstick in the diagnosis of human leptospirosis allows providing a rapid response to the medical staff in charge of the studied cases. This proved that Lepto-dipstick is a rapid method that is easy-to-read and interpret.


Inhibition of human polymorphonuclear leukocyte function by 2-cyclohexene-1-one. A role for glutathione in cell activation.
2-cyclohexene-1-one and diethyl maleate specifically decrease reduced glutathione (GSH) levels in human polymorphonuclear leukocytes (PMN) by direct conjugation, and by interaction with the glutathione-s-transferase system. Using these two nontoxic reagents we have examined the effect of decreased GSH levels on five parameters of PMN activation: superoxide generation, release of the lysosomal enzymes lysozyme and beta-glucuronidase, and increases in the influx of Na+ and Ca2+. When PMN pretreated with 2-cyclohexene-1-one or diethyl maleate were incubated with formyl-methionyl-leucyl-phenylalanine (FMLP) or the proteolytic fragment of the fifth component membrane of complement, C5a, agents that interact with surface membrane receptors, increases in all five parameters were inhibited in a dose-dependent manner. For O-2 generation and lysosomal enzyme release the ID50 for 2-CHX-1 was 40--90 micrometers corresponding with a 30--50% decrease in intracellular GHS. In contrast stimulation of treated PMN by the divalent cation ionophore A23187 or 5-hydroxyeicosatetraenoic acid was much less sensitive to depressed GSH; the ID50 for 2-cyclohexene-1-one was 1 mM or greater, corresponding with an 80--90% decrease in GSH. The effect of lowered GSH was not the result of decreased binding of FMLP to surface receptors because [3H]-FMLP binding studies demonstrated a two- to three-fold increase in the number of available binding sites. These data indicate that normal GSH levels are necessary for the transduction of the activation signal from the exterior to the interior of the PMN, but once initiated the activation sequence proceeds normally despite markedly lowered intracellular GSH.


Immunological phenotype of lymphomas induced by avian leukosis viruses.
The production of immunoglobulin by six cell lines derived from bursal tumors induced by avian leukosis virus follows two general patterns: (i) three cell lines that have been extensively passaged in culture synthesize and secrete light chains only; (ii) three cell lines that are recently isolated produce and secrete monomeric immunoglobulin M in addition to free light chains. All six cell lines synthesize and secrete both glycosylated and unglycosylated forms of light chain. We conclude that the cell lines established from lymphomas induced by avian leukosis virus represent relatively mature, but possibly abnormal, stages in the development of chicken B-lymphocytes. The immunoglobulin M produced by the cell lines failed to form detectable immune complexes with avian leukosis virus. It therefore appears that the immunoglobulin M is not directed against viral antigens and that autogenous antigenic stimulus cannot account for the sustained growth of the neoplastic B-lymphocytes.


Long Volar Plating for Metadiaphyseal Fractures of Distal Radius: Study Comparing Minimally Invasive Plate Osteosynthesis versus Conventional Approach.
Background Minimally invasive plate osteosynthesis (MIPO) has been used in wrist surgery for several years. The purpose of this retrospective study was to compare clinical and radiologic outcomes of MIPO technique with those of a conventional approach in the treatment of metadiaphyseal distal radius fracture by long volar plating. Materials and Methods Our series consisted of 32 fractures in 31 patients, mean age 63.9 years, including 16 men and 15 women. MIPO technique was used in 15 wrists (group 1) and conventional approach (> 60 mm of skin incision) in 17 wrists (group 2). In group 1, a long volar plate was inserted under pronator quadratus through a 15- to 30-mm distal incision then fixed to the epiphysis of the distal radius. Then, through a 15- to 30-mm proximal incision, the plate was fixed to the diaphysis of the radius, thus reducing the fracture. Results In group 1, mean distal incision size was 23.5 and 16.9 mm for proximal one. Mean total scar size (sum of both distal and proximal incisions) was 40.0 mm in group 1 and 84.1 mm in group 2. Mean tourniquet time was 58.4 minutes in group 1 and 68.9 minutes in group 2. At latest follow-up, no significant difference was noted in both the groups concerning pain, quick-DASH score, grip strength, ROM, and radiologic data. One extensor pollicis longus rupture treated by tendon transfer was done in group 1. Conclusion The MIPO technique for metadiaphyseal fractures of the distal radius by long volar plating has cosmetic and economic advantages compared with the conventional approach. Conversion to conventional approach is possible at any time in case of technical difficulties. Level of Evidence III.


Effects of egg as an early complementary food on growth of 6 to 9-month-old infants: A randomised controlled trial.
To assess the effect of daily egg consumption for six months on linear growth (primary outcome), weight-for-age, weight-for-length, mid-upper arm circumference-for-age, and head circumference-for-age Z-scores, gross motor milestones development, anaemia, and iron status (secondary outcomes) in a low socioeconomic community. Infants aged 6 to 9-months living in peri-urban Jouberton area, in the Matlosana Municipality, South Africa. A randomised controlled trial with a parallel design was implemented. Eligible infants were randomly allocated to the intervention (n = 250) receiving one egg/day and the control group (n = 250) receiving no intervention. The participants were visited weekly to monitor morbidity and gross motor development, with information on adherence collected for the intervention group. Trained assessors took anthropometric measurements, and a blood sample was collected to assess anaemia and iron status. There was blinding of the anthropometric assessors to the groups during measurements and the statistician during the analysis. Baseline prevalence of stunting, underweight, wasting, overweight and anaemia was 23.8%, 9.8%, 1.2%, 13.8%, and 29.2%, respectively, and did not differ between groups. Overall, 230 and 216 participants in the intervention and control groups completed the study, respectively. There was no intervention effect on length-for-age, weight-for-age, weight-for-length Z-scores, gross motor milestone development, anaemia, and iron status. Daily egg intake did not affect linear growth, underweight, wasting, motor milestones development, anaemia, and iron status. Other interventions are necessary to understand the effect of animal-source food intake on children's growth and development. This trial was registered at https://clinicaltrials.gov/ (NCT05168085).


Automatic workflow for the classification of local DNA conformations.
A growing number of crystal and NMR structures reveals a considerable structural polymorphism of DNA architecture going well beyond the usual image of a double helical molecule. DNA is highly variable with dinucleotide steps exhibiting a substantial flexibility in a sequence-dependent manner. An analysis of the conformational space of the DNA backbone and the enhancement of our understanding of the conformational dependencies in DNA are therefore important for full comprehension of DNA structural polymorphism. A detailed classification of local DNA conformations based on the technique of Fourier averaging was published in our previous work. However, this procedure requires a considerable amount of manual work. To overcome this limitation we developed an automatic classification method consisting of the combination of supervised and unsupervised approaches. A proposed workflow is composed of k-NN method followed by a non-hierarchical single-pass clustering algorithm. We applied this workflow to analyze 816 X-ray and 664 NMR DNA structures released till February 2013. We identified and annotated six new conformers, and we assigned four of these conformers to two structurally important DNA families: guanine quadruplexes and Holliday (four-way) junctions. We also compared populations of the assigned conformers in the dataset of X-ray and NMR structures. In the present work we developed a machine learning workflow for the automatic classification of dinucleotide conformations. Dinucleotides with unassigned conformations can be either classified into one of already known 24 classes or they can be flagged as unclassifiable. The proposed machine learning workflow permits identification of new classes among so far unclassifiable data, and we identified and annotated six new conformations in the X-ray structures released since our previous analysis. The results illustrate the utility of machine learning approaches in the classification of local DNA conformations.


Emotion regulation and heterogeneity in attention-deficit/hyperactivity disorder.
How best to capture heterogeneity in attention-deficit/hyperactivity disorder (ADHD) using biomarkers has been elusive. This study evaluated whether emotion reactivity and regulation provide a means to achieve this. Participants were classified into three groups: children with ADHD plus low prosocial behavior (hypothesized to be high in callous/unemotional traits; n = 21); children with ADHD with age-appropriate prosocial behavior (n = 54); and typically developing children (n = 75). Children completed a task with four conditions: negative induction, negative suppression, positive induction, and positive suppression of affect. The task required children to view an emotion-laden film clip, while either facially mimicking (induction) or masking (suppression) the emotion of the main character. Parasympathetic and sympathetic nervous system activity were assessed via respiratory sinus arrhythmia (RSA) and cardiac pre-ejection period (PEP), respectively. Symptoms of anxiety, conduct, and oppositional defiant disorders were treated as covariates. The ADHD-typical-prosocial group displayed atypically elevated parasympathetic reactivity (emotion dysregulation) during positive induction, along with increased sympathetic activity (elevated arousal) across conditions. In contrast, the ADHD-low-prosocial group displayed reduced parasympathetic reactivity and reduced sympathetic activity (low emotional arousal) across baseline and task conditions. Thus, both ADHD groups had altered patterns of autonomic functioning, but in two distinct forms. Although ADHD is heterogeneous clinically, results suggest that ADHD is also heterogeneous with regard to physiological indices of emotion and regulation. Future studies of emotion, regulation, and ADHD should take this into account. Further study of physiological responding in ADHD may yield clinically and etiologically distinct domains or groups.


Design of photocaged puromycin for nascent polypeptide release and spatiotemporal monitoring of translation.
The antibiotic puromycin, which inhibits protein translation, is used in a broad range of biochemical applications. The synthesis, characterization, and biological applications of NVOC-puromycin, a photocaged derivative that is activated by UV illumination, are presented. The caged compound had no effect either on prokaryotic or eukaryotic translation or on the viability of HEK 293 cells. Furthermore, no significant release of ribosome-bound polypeptide chains was detected in vitro. Upon illumination, cytotoxic activity, in vitro translation inhibition, and polypeptide release triggered by the uncaging of NVOC-puromycin were equivalent to those of the commercial compound. The quantum yield of photolysis was determined to be 1.1±0.2% and the NVOC-puromycin was applied to the detection of newly translated proteins with remarkable spatiotemporal resolution by using two-photon laser excitation, puromycin immunohistochemistry, and imaging in rat hippocampal neurons.


Rethinking Disentanglement in Unsupervised Domain Adaptation for Medical Image Segmentation.
Domain adaptation has become an important topic because the trained neural networks from the source domain generally perform poorly in the target domain due to domain shifts, especially for medical image analysis. Previous DA methods mainly focus on disentangling domain features. However, it is based on feature independence, which often can not be guaranteed in reality. In this work, we present a new DA approach called Dimension-based Disentangled Dilated Domain Adaptation (D4A) to disentangle the storage locations between the features to tackle the problem of domain shift for medical image segmentation tasks without the annotations of the target domain. We use Adaptive Instance Normalization (AdaIN) to encourage the content information to be stored in the spatial dimension, and the style information to be stored in the channel dimension. In addition, we apply dilated convolution to preserve anatomical information avoiding the loss of information due to downsampling. We validate the proposed method for cross-modality medical image segmentation tasks on two public datasets, and the comparison experiments and ablation studies demonstrate the effectiveness of our method, which outperforms the state-of-the-art methods.