Neuroimaging abnormalities in patients with Cowden syndrome: Retrospective single-center study.
We retrospectively reviewed the neuroimaging findings of patients with Cowden syndrome and determined their frequency in a single cohort. Electronic medical records were queried from January 1999 to January 2017 to identify patients who fit the clinical criteria for diagnosis of Cowden syndrome with or without a documented PTEN mutation. Patients with brain MRI examinations were then identified. We retrospectively identified 44 patients with Cowden syndrome, 22 of whom had neuroimaging for review. Eleven (50%) had Lhermitte-Duclos disease, 4 (18.1%) had meningiomas, 13 (59.1%) had at least one developmental venous anomaly, 3 had cavernous malformations, 2 had evidence of dural arteriovenous fistula, 7 had increased white matter signal abnormalities relative to age (31.8%), 4 had prominent perivascular spaces, cerebellar tonsillar ectopia was present in 7 of 21 (33.3%), and 1 had cortical malformation. It is important to recognize that in addition to Lhermitte-Duclos disease, other intracranial findings such as multiple venous anomalies, meningiomas, greater than expected white matter signal abnormality, prominent perivascular spaces, and cortical malformations may warrant a thorough evaluation for Cowden syndrome in the appropriate clinical setting. We further recommend that this broader spectrum of intracranial abnormalities be considered for addition to the Cowden syndrome diagnostic criteria at the time of next revision.


Nasal augmentation using Gore-Tex. A 10-year experience.
To determine on an ongoing basis the safety and efficacy of expanded polytetrafluoroethylene (Gore-Tex soft tissue patch and preformed nasal implants) as an implant in rhinoplasty. A retrospective study of 309 consecutive patients who underwent rhinoplasty, including augmentation with Gore-Tex, during a 10-year period. Two major academic medical centers and 2 private office surgical centers. One hundred sixty-two patients (52%) presented for primary rhinoplasty; the remaining 147 (48%) presented for revision surgery. All received Gore-Tex implants to augment the nasal dorsum and/or base. The grafts ranged from 1 to 10 mm in thickness. Follow-up ranged from 5 months to 10 years, 5 months, with an average of 40.4 months. Clinically noted complications and patient satisfaction. Ten (3.2%) of 309 grafts became infected and were removed. One graft was removed and 1 graft was modified and replaced postoperatively because of excessive augmentation. Infection requiring removal occurred in 8 patients (5.4%) undergoing revision rhinoplasty and in 2 patients (1.2%) undergoing primary rhinoplasty. Nasal septal perforation was present preoperatively in 3 of the patients who developed infection requiring removal, and we consider it a contraindication for nasal Gore-Tex implantation. Gore-Tex remains an effective implant material for nasal augmentation in rhinoplasty. The complication rate in primary cases is low. The risk of infection necessitating removal rises significantly in revision cases, where its use may still be desirable but must be weighed more carefully.


[Leg amputation for severe lower limb ischemia caused by type A acute aortic dissection; report of a case].
A 41-year-old man underwent total arch replacement and aorto-bifemoral bypass owing to type A acute aortic dissection complicated by ischemia of both lower extremities. Just after the operation, he developed myonephropathic metabolic syndrome due to severe ischemia of the right leg, and hemodiafiltration was performed. However, the serum potassium was elevated to an uncontrollable level. Ligation of the right femoral artery and the right branch of the bypass graft was performed one hour after the transfer to intensive care unit (ICU), and the serum potassium dropped to a normal level. He underwent amputation of the right lower limb above the knee on the 13th postoperative day, and was discharged after long-term rehabilitation.


Effects of ozone applied by spinal endoscopy in patients with chronic pain related to failed back surgery syndrome: a pilot study.
In the last two decades, ozone has emerged as a treatment for low back pain, applied by means of minimally invasive techniques. The aim of this study is to assess the effect and safety of ozone therapy applied in the epidural space for chronic pain related to failed back surgery syndrome. The investigators studied 13 sequential patients of both sexes, between 18 and 70 years old, with persistent chronic pain (more than six months) in the lumbar region and in the lower limbs related to failed back surgery syndrome (FBSS). Pain was classified as neuropathic and non-neuropathic regarding the topography (lumbar and lower limb), based on the DN4 (Douleur Neuropathique 4) questionnaire. The patients received the ozone gas in the lumbar epidural space via spinal-sacral endoscopy. Clinical evaluation was performed before, immediately after (24 hours), and 1, 3, and 6 months after intervention with visual analog scale and Oswestry Disability Index (ODI). Overall, the patients had 43.7% reduction of lumbar pain, 60.9% reduction in leg pain in six months followed by 44.0% of improvement in ODI. The reduction of pain and in the disability index was markedly greater in patients with non-neuropathic predominant pain, 95.2%, 80.6%, and 75.3% improvement in lumbar, leg pain, and ODI respectively, while neuropathic predominant pain patients experienced only 12.5%, 42.4%, and 20.9% improvement, also respectively. No neurological or infectious complications were observed acutely or during the follow-up. The present data suggests that epidural ozone might be a therapeutic option for persistent low back pain, especially in non-neuropathic predominant pain patients, but double-blind controlled studies are still required to prove its efficacy.


Transcrocetin meglumine salt inhibits spinal glial cell-mediated proinflammatory cytokines and attenuates complete Freund's adjuvant-induced inflammatory pain.
Inflammatory pain is a significant global clinical challenge that involves both unpleasant sensory and emotional experiences. The treatment of pain is imminent, and we are committed to seeking new analgesics for pain relief. Transcrocetin meglumine salt (TCMS), a saffron metabolite derived from the crocin apocarotenoids, has exhibited the ability to cross the blood-brain barrier and exert neuroprotective effects. In this study, we aimed to investigate whether TCMS could ameliorate complete Freund's adjuvant (CFA)-induced inflammatory pain in mice and elucidate its underlying mechanisms. Here, we established an inflammatory pain model in mice by injecting CFA into the left hind paw. Three days later, we administered intraperitoneal injections of TCMS (10mg/kg) or saline to the animals. We examined mechanical allodynia, thermal hypersensitivity, and anxiety behavior. Furthermore, the activation of glial cells and proinflammatory cytokines in the spinal cord were detected. Our results showed that TCMS significantly reversed the mechanical allodynia and thermal hypersensitivity in the CFA-injected mice. Furthermore, TCMS administration effectively inhibited the activation of microglia and astrocytes in the spinal cord induced by CFA. Additionally, TCMS suppressed the production and release of spinal proinflammatory cytokines, including TNF-α, IL-1β, and IL-6, in CFA-injected mice. Taken together, our findings demonstrate that TCMS holds promise as an innovative analgesic due to its ability to ameliorate inflammatory reactions.


The Effect of Lactic Acid Bacteria-fermented Soybean Milk Products on Carrageenan-induced Tail Thrombosis in Rats.
Thrombosis is characterized by congenital and acquired procatarxis. Lactic acid bacteria-fermented soybean milk products (FS-LAB) inhibit hepatic lipid accumulation and prevent atherosclerotic plaque formation. However, the therapeutic efficacy of FS-LAB against thrombosis has yet to be investigated. In this study, FS-LAB were administered subcutaneously into the tails of rats, with the subsequent intravenous administration of κ-carrageenan 12 hr after the initial injection. In general, administration of κ-carrageenan induces thrombosis. The length of the infarcted tail regions was significantly shorter in the rats administered a single-fold or double-fold concentration of the FS-LAB solution compared with the region in control rats. Therefore, FS-LAB exhibited significant antithrombotic effects. Our study is the first to characterize the properties of FS-LAB and, by testing their efficacy on an in vivo rat model of thrombosis, demonstrate the potency of their antithrombotic effect.


Approaches to design non-covalent inhibitors for human granzyme B (hGrB).
A structure-based design campaign for non-covalent small molecule inhibitors of human granzyme B was carried out by means of a virtual screening strategy employing three constraints and probe site-mapping with FTMAP to identify ligand "hot spots". In addition, new scaffolds of diverse structures were subsequently explored with ROCS shape-based superposition methods, following by Glide SP docking, induced fit docking and analysis of QikProp molecular properties. Novel classes of moderately active small molecule blockers (≥25 μM IC50 values) from commercially available libraries were identified, and three novel scaffolds have been synthesized by multi-step procedures. Furthermore, we provide an example of a comprehensive structure-based drug discovery approach to non-covalent inhibitors that relies on the X-ray structure of a covalently bound ligand and suggest that the design path may be compromised by alternative and unknown binding poses.


Synthesis and crystal structure of As-synthesized and calcined pure silica zeolite ITQ-12.
The small-pore pure silica zeolite ITQ-12 has been synthesized with fumed silica as the silica source in the presence of 1,3,4-trimethylimidazolium hydroxide and hydrofluoric acid under hydrothermal conditions at 448 K. Rietveld refinement using synchrotron X-ray diffraction data of the calcined ITQ-12 product taken at 298 K confirms the proposed topology, framework type code ITW, which can be described by a monoclinic unit cell [Si(24)O(48)] having Cm symmetry. Unit cell parameters are a = 10.3360(4), b = 15.0177(6), and c = 8.8639(4) A, beta = 105.356(3) degrees, and cell volume V = 1326.76(9) A(3). For as-synthesized ITQ-12, the occluded fluoride anion is located inside the double four-membered ring, while the flat 1,3,4-trimethylimidazolium cation lies on the equatorial plane of the slit-shaped [4(4)5(4)6(4)8(4)] cage, with its longest dimension in the [010] direction. The monoclinic unit cell |(C(6)N(2)H(11))(+)(2)F(-)(2)|[Si(24)O(48)], having Cm symmetry, has parameters a = 10.4478(3), b = 14.9854(4), and c = 8.8366(3) A, beta = 105.935(2) degrees, and cell volume V = 1330.34(7) A(3) at 298 K. Cooperative structure-directing effects during the crystallization of ITQ-12 are discussed in terms of the structure of the as-made material.


Quantitative Modeling and Automated Analysis of Meiotic Recombination.
Many morphological features, in both physical and biological systems, exhibit spatial patterns that are specifically characterized by a tendency to occur with even spacing (in one, two, or three dimensions). The positions of crossover (CO) recombination events along meiotic chromosomes provide an interesting biological example of such an effect. In general, mechanisms that explain such patterns may (a) be mechanically based, (b) occur by a reaction-diffusion mechanism in which macroscopic mechanical effects are irrelevant, or (c) involve a combination of both types of effects. We have proposed that meiotic CO patterns arise by a mechanical mechanism, have developed mathematical expressions for such a process based on a particular physical system with analogous properties (the so-called beam-film model), and have shown that the beam-film model can very accurately explain experimental CO patterns as a function of the values of specific defined parameters. Importantly, the mathematical expressions of the beam-film model can apply quite generally to any mechanism, whether it involves mechanical components or not, as long as its logic and component features correspond to those of the beam-film system. Furthermore, via its various parameters, the beam-film model discretizes the patterning process into specific components. Thus, the model can be used to explore the theoretically predicted effects of various types of changes in the patterning process. Such predictions can expand detailed understanding of the bases for various biological effects. We present here a new MATLAB program that implements the mathematical expressions of the beam-film model with increased robustness and accessibility as compared to programs presented previously. As in previous versions, the presented program permits both (1) simulation of predicted CO positions along chromosomes of a test population and (2) easy analysis of CO positions, both for experimental data sets and for data sets resulting from simulations. The goal of the current presentation is to make these approaches more readily accessible to a wider audience of researchers. Also, the program is easily modified, and we encourage interested users to make changes to suit their specific needs. A link to the program is available on the Kleckner laboratory website: http://projects.iq.harvard.edu/kleckner_lab .


Cytoplasmic dynein-mediated assembly of pericentrin and gamma tubulin onto centrosomes.
Centrosome assembly is important for mitotic spindle formation and if defective may contribute to genomic instability in cancer. Here we show that in somatic cells centrosome assembly of two proteins involved in microtubule nucleation, pericentrin and gamma tubulin, is inhibited in the absence of microtubules. A more potent inhibitory effect on centrosome assembly of these proteins is observed after specific disruption of the microtubule motor cytoplasmic dynein by microinjection of dynein antibodies or by overexpression of the dynamitin subunit of the dynein binding complex dynactin. Consistent with these observations is the ability of pericentrin to cosediment with taxol-stabilized microtubules in a dynein- and dynactin-dependent manner. Centrosomes in cells with reduced levels of pericentrin and gamma tubulin have a diminished capacity to nucleate microtubules. In living cells expressing a green fluorescent protein-pericentrin fusion protein, green fluorescent protein particles containing endogenous pericentrin and gamma tubulin move along microtubules at speeds of dynein and dock at centrosomes. In Xenopus extracts where gamma tubulin assembly onto centrioles can occur without microtubules, we find that assembly is enhanced in the presence of microtubules and inhibited by dynein antibodies. From these studies we conclude that pericentrin and gamma tubulin are novel dynein cargoes that can be transported to centrosomes on microtubules and whose assembly contributes to microtubule nucleation.


Applications of molecular MRI and optical imaging in cancer.
Some of the most exciting advances in molecular-functional imaging of cancer are occurring at the interface between chemistry and imaging. Several of these advances have occurred through the development of novel imaging probes that report on molecular pathways, the tumor micro-environment and the response of tumors to treatment; as well as through novel image-guided platforms such as nanoparticles and nanovesicles that deliver therapeutic agents against specific targets and pathways. Cancer cells have a remarkable ability to evade destruction despite the armamentarium of drugs currently available. While these drugs can destroy cancer cells, normal tissue toxicity is a major limiting factor, a problem further compounded by poor drug delivery. One major challenge for chemistry continues to be to eliminate cancer cells without damaging normal tissues. Here we have selected examples of MRI and optical imaging, to demonstrate how integrating imaging with novel probes can facilitate the successful treatment of this multifaceted disease.


Acetaminophen does not affect cardiac and brain responses to social rejection but seems to attenuate behavioral adaptation in a social judgment task.
The present study examined the effect of Acetaminophen on the painful experience of social rejection by examining brain, cardiac and behavioral measures reflecting different aspects of social feedback processing. Healthy students (N = 72), after ingesting either Acetaminophen or a placebo, performed a social judgment paradigm (SJP), in which they could be expectedly or unexpectedly rejected or accepted. During the task, cardiac and brain responses to different types of feedback were measured, as well as expectancies relating to the given feedback. Enhanced cardiac deceleration was found after unexpected social rejection as compared to all other conditions. Larger mean P3 amplitude was found after expected positive and negative feedback stimuli as compared to unexpected stimuli. While cardiac deceleration and P3 were not affected by Acetaminophen, behavioral responses were. While in the control group the percentage of acceptance predictions decreased over the experiment (learning from negative feedback), the Acetaminophen group did not adjust their positive prediction bias over time. The unexpected effect of Acetaminophen on prediction behavior suggests that Acetaminophen might indeed play a role in social pain perception. The normally observed social pain-based learning effect seems to disappear when participants ingest Acetaminophen, which can be interpreted as a reduced pain perception after Acetaminophen.


A multi-perspective cost-effectiveness analysis comparing rivaroxaban with enoxaparin sodium for thromboprophylaxis after total hip and knee replacement in the German healthcare setting.
Patients undergoing major orthopaedic surgery (MOS), such as total hip (THR) or total knee replacement (TKR), are at high risk of developing venous thromboembolism (VTE). For thromboembolism prophylaxis, the oral anticoagulant rivaroxaban has recently been included in the German diagnosis related group (DRG) system. However, the cost-effectiveness of rivaroxaban is still unclear from both the German statutory health insurance (SHI) and the German hospital perspective. To assess the cost-effectiveness of rivaroxaban from the German statutory health insurance (SHI) perspective and to analyse financial incentives from the German hospital perspective. Based on data from the RECORD trials and German cost data, a decision tree was built. The model was run for two settings (THR and TKR) and two perspectives (SHI and hospital) per setting. Prophylaxis with rivaroxaban reduces VTE events (0.02 events per person treated after TKR; 0.007 after THR) compared with enoxaparin. From the SHI perspective, prophylaxis with rivaroxaban after TKR is cost saving (€27.3 saving per patient treated). However, the cost-effectiveness after THR (€17.8 cost per person) remains unclear because of stochastic uncertainty. From the hospital perspective, for given DRGs, the hospital profit will decrease through the use of rivaroxaban by €20.6 (TKR) and €31.8 (THR) per case respectively. Based on our findings, including rivaroxaban for reimbursement in the German DRG system seems reasonable. Yet, adequate incentives for German hospitals to use rivaroxaban are still lacking.


A study of the effects of exercise on the urinary metabolome using normalisation to individual metabolic output.
Aerobic exercise, in spite of its multi-organ benefit and potent effect on the metabolome, has yet to be investigated comprehensively via an untargeted metabolomics technology. We conducted an exploratory untargeted liquid chromatography mass spectrometry study to investigate the effects of a one-h aerobic exercise session in the urine of three physically active males. Individual urine samples were collected over a 37-h protocol (two pre-exercise and eight post-exercise). Raw data were subjected to a variety of normalization techniques, with the most effective measure dividing each metabolite by the sum response of that metabolite for each individual across the 37-h protocol expressed as a percentage. This allowed the metabolite responses to be plotted on a normalised scale. Our results highlight significant metabolites located in the following systems: purine pathway, tryptophan metabolism, carnitine metabolism, cortisol metabolism, androgen metabolism, amino acid oxidation, as well as metabolites from the gastrointestinal microbiome. Many of the significant changes observed in our pilot investigation mirror previous research studies, of various methodological designs, published within the last 15 years, although they have never been reported at the same time in a single study.


Data Custodians and the Decision-making Process: Releasing Data for Research.
The empirical research presented in this article was prompted by concerns expressed by researchers about the decision-making processes of government data custodians. Data custodians are responsible for the collection, use and disclosure of vast collections of personal information, including the release of data from these collections for research. Researchers were concerned that the decision-making processes were time-consuming, complex and not transparent. The authors sought the views of data custodians in response, exploring the issues from the other side of the data divide. The majority of the 13 data custodians interviewed for this project were located in government sector agencies and their decision-making process was thus highly regulated and constrained by principles of administrative law. They did, however, have many thoughtful suggestions for change to improve the experience for all the stakeholders involved in the process of seeking and granting access to government-held data collections for research.


Large Language Model-based Chatbot as a Source of Advice on First Aid in Heart Attack.
The ability of the cutting-edge large language model-powered chatbots to generate human-like answers to user questions hypothetically could be utilized for providing real-time advice on first aid for witnesses of cardiovascular emergencies. This study aimed to evaluate quality of the chatbot responses to inquiries on help in heart attack. The study simulated interrogation of the new Bing chatbot (Microsoft Corporation, USA) with the "heart attack what to do" prompt coming from 3 countries, the Gambia, India and the USA. The chatbot responses (20 per country) were evaluated for congruence with the International First Aid, Resuscitation, and Education Guidelines 2020 using a checklist. For all user inquiries, the chatbot provided answers containing some guidance on first aid. However, the responses commonly left out some potentially life-saving instructions, for instance to encourage the person to stop physical activity, to take antianginal medication, or to start cardiopulmonary resuscitation for unresponsive abnormally breathing person. Mean percentage of the responses having full congruence with the checklist criteria varied from 7.3 for India to 16.8 for the USA. A quarter of responses for the Gambia and the USA, and 45.0% for India contained superfluous guidelines-inconsistent directives. The chatbot advice on help in heart attack has omissions, inaccuracies and misleading instructions, and therefore the chatbot cannot be recommended as a credible source of information on first aid. Active research and organizational efforts are needed to mitigate the risk of uncontrolled misinformation and establish measures for guaranteeing trustworthiness of the chatbot-mediated counseling.


Use of octogenarian livers safely expands the donor pool.
The increasing number of recipients on the waiting list for orthotopic liver transplantation (OLT) and the scarcity of donors contribute to recipient pretransplantation mortality. One important measure to increase the donor liver pool would be to accept the previously discarded donors who are more than 80 years old. From November 1996 to May 1998, four liver grafts from octogenarian donors (89, 87, 82, and 85 years old, respectively) were used for OLT. Pretransplantation donor and recipient characteristics and the evolution of recipients after OLT were analyzed. The donors did not present cardiac arrest or hypotension, and only low doses of vasopressors were required in three of them. Intensive care unit stay of the donors was from 12 to 24 hr. Cold ischemia time was from 4 hr to 8 hr 40 min. Mild microsteatosis was present in three donors and associated macrosteatosis of < 10% in one of these. Macroscopic appearance and consistency were normal in all four grafts. Posttransplantation evolution and follow-up were uneventful. Three recipients were alive and well at 24, 16, and 7 months; the second of these died at 16 months of recurrent viral C cirrhosis after a first OLT. The liver donor pool can be increased if liver grafts are accepted without an age limit but in good condition (hemodynamic stability, short intensive care unit stay, good liver function, soft consistency, cold ischemia time <9 hr, and no severe steatosis). Octogenarian donors should be individually assessed in the absence of these ideal conditions.


Ginkgo biloba extract postconditioning reduces myocardial ischemia reperfusion injury.
We examined the protective effects of Ginkgo biloba extract (EGb761) postconditioning on myocardial ischemia reperfusion injury in rabbits. Four groups of 8 white rabbits were allocated to: pseudo surgery group: the left coronary was lined without blocking for 160 min after thoracotomy; ischemia and reperfusion group (IR): the left anterior descending coronary artery was blocked for 40 min and reperfused for 120 min; ischemic postconditioning group: the left anterior descending artery was ligated for 40 min, reopened for 30 s and ligated for 30 s, repeated three times, and then reperfused for 120 min; EGb761 postconditioning group (E): 100 mg/kg EGb761 was injected into a vein while the left coronary artery was opened for 1 min. The reperfusion took 120 min. Internal carotid arterial blood in each group was collected for cTnI measurement at five times: 20 min before occlusion of the left coronary artery, 20 min after left coronary artery occlusion, 40 min after left coronary artery occlusion, 1 h after myocardial reperfusion, and 2 h after myocardial reperfusion. Superoxide dismutase (SOD), malondialdehyde (MDA) in the centrifuged blood and myocardial infarction area were measured at the end of reperfusion. We found that the serum cTnI concentrations in the E group during reperfusion decreased significantly compared with those in the IR group. The infarction area was significantly lower in the E group than that in the IR group. The SOD activity in the E group was increased compared with that in the IR group; the MDA content decreased significantly in the E group compared with that in the IR group. We conclude that G. biloba extract postconditioning had myocardial protection effects by reducing the generation of oxygen-free radicals and increasing the antioxidant capacity of the myocardial cells.


Tuberculum sellae meningiomas: surgical technique, visual outcome, and prognostic factors in 51 cases.
Complete tumor resection with preservation or improvement of visual function is the goal of tuberculum sellae meningioma (TSM) treatment. The authors retrospectively reviewed 51 patients treated surgically for TSM between 2003 and 2010, with special attention to surgical technique, visual outcomes, and prognostic factors for treatment outcome. All patients were operated via the lateral subfrontal approach. The cohort mean age and Karnofsky performance status (KPS) on admission was 57.1 ± 13.6 and 84.3 ± 11.7, respectively. The most common presenting sign was visual impairment. The mean tumor size was 29.4 ± 10.7 mm. In 45 of the patients (88.2%), gross total resection was achieved. Improvement and/or preservation of visual acuity and visual field were achieved in 95.9% and 85.3%, respectively. Visual functions on admission were found to be the strongest predictors for postoperative improvement in visual outcome, followed by better KPS on admission, smaller tumor size, and young age. Postoperative neurological complications included cerebrospinal fluid (CSF) leak, meningitis, and postoperative seizures. TSM can be safely operated on through the lateral subfrontal approach. A high percentage of complete tumor resection and excellent visual outcomes are achieved using this technique. Surgical treatment in the early stage of the disease may result in a better visual outcome.


IV Sotalol Use in Pediatric and Congenital Heart Patients: A Multicenter Registry Study.
Background There is limited information regarding the clinical use and effectiveness of IV sotalol in pediatric patients and patients with congenital heart disease, including those with severe myocardial dysfunction. A multicenter registry study was designed to evaluate the safety, efficacy, and dosing of IV sotalol. Methods and Results A total of 85 patients (age 1 day-36 years) received IV sotalol, of whom 45 (53%) had additional congenital cardiac diagnoses and 4 (5%) were greater than 18 years of age. In 79 patients (93%), IV sotalol was used to treat supraventricular tachycardia and 4 (5%) received it to treat ventricular arrhythmias. Severely decreased cardiac function by echocardiography was seen before IV sotalol in 7 (9%). The average dose was 1 mg/kg (range 0.5-1.8 mg/kg/dose) over a median of 60 minutes (range 30-300 minutes). Successful arrhythmia termination occurred in 31 patients (49%, 95% CI [37%-62%]) with improvement in rhythm control defined as rate reduction permitting overdrive pacing in an additional 18 patients (30%, 95% CI [19%-41%]). Eleven patients (16%) had significant QTc prolongation to >465 milliseconds after the infusion, with 3 (4%) to >500 milliseconds. There were 2 patients (2%) for whom the infusion was terminated early. Conclusions IV sotalol was safe and effective for termination or improvement of tachyarrhythmias in 79% of pediatric patients and patients with congenital heart disease, including those with severely depressed cardiac function. The most common dose, for both acute and maintenance dosing, was 1 mg/kg over ~60 minutes with rare serious complications.


[Bogorad syndrome or crocodile tears after Ramsay-Hunt].
Crocodile tears or Bogorad Syndrome describes a complication or sequel after facial palsy with incomplete recovery characterized by an excessive hyperlacrimation during the food ingestion. We report the case of a 50 years old female with that pathology associated to facial syncinesias secondary to suffer a right Ramsay-Hunt syndrome. Its pathogenesis and different treatment modalities are analysed.


Effects of lipopolysaccharide on the blood-brain barrier permeability in prolonged nitric oxide blockade-induced hypertensive rats.
The authors investigated the effects of lipopolysaccharide (LPS) on the blood-brain barrier (BBB) integrity and the activity of astrocytes during the Nw-nitro-L-arginine methyl ester (L-NAME) hypertension followed by angiotensin (ANG) II in rats. They measured the changes in the BBB permeability using the Evans blue (EB) dye and concomitantly in the levels of TNF-a, IL-1b, and IL-6 in serum and nitric oxide in plasma. The authors performed two tight junction-specific proteins, zonula occludens-1 and occludin, and glial fibrillary acidic protein, by using immunohisto-chemical method. The serum levels of TNF-a, IL-1 IL-6, and the plasma level of nitric oxide significantly increased in LPS-treated rats (p<.01). The EB dye extravasation increased in cerebellum (p<.001) and diencephalon (p<.05) of L-NAME plus ANG II-treated animals. However, LPS reduced the increased EB dye extravasation in the brain regions of L-NAME-induced hypertensive rats treated with ANG II (p<.001). In L-NAME, there was a considerable loss of staining in both zonula occludens-1 and occludin. Staining for zonula occludens-1 and occludin was highly intensive in animals treated with LPS. Glial fibrillary acidic protein staining was seen in a few astrocytes in brains of L-NAME-treated animals. However, this staining showed an increased intensity in the brain sections of animals treated with LPS. This study indicates that, in L-NAME hypertensive rats, ANG II leads to an increase in the extravasation of EB dye to brain as a result of decreased activity of tight junction proteins and astrocytes, and LPS could significantly attenuate the EB dye transport to the brain through the increased activity of tight junction proteins and astrocytes.


[Effect of intrathecal pumping tramadol on the immune function in rats with formalin pain].
To evaluate the effect of intrathecal pumping tramadol on cell-mediated immunity in rats with formalin inflammatory pain. Thirty-two Sprague-Dawley adult male rats weighting 250 approximately 300 g were randomly divided into 4 groups (n=8 in each group):Saline group (NS) and 3 tramadol groups (T1,T2,and T3). The rats were anesthetized with intraperitoneal chloral hydrate (300 approximately 350)mg/kg. Microspinal catheter was inserted into the subarachnoid space at the lumber region according to modified Yaksh techniques. In the tramadol groups,after 5 days tramadol was continuously infused through the spinal catheter at 50 (T1),25 (T2), and 12.5 microg/h (T3) for 7 days. In the NS group normal saline was continuously infused instead of tramadol. On Day 7 formalin (5%, 50 microL) was injected into the plantar surface of the left hindpaw. The number of flinches, lickings and total time of licking was recorded for 60 min.Pain intensity scoring(PIS)(0 approximately 3;0= no pain, 3=severe pain) was used to assess the antinociceptive effect of intrathecal tramadol. The rats were killed after the evaluation of pain intensity. Body weight and spleen weight were measured and spleen index (spleen weight/body weight) was calculated. T-lymphocyte function was evaluated based on Concanavalin-A(ConA) induced splenocyte proliferation. A modified lactic acid dehydrogenase(LDH) release assay was done to assess the NK cell activity. Phenotypic expressions of cell surface markers of T lymphocyte subsets (CD3+, CD3+ CD4+, CD3+ CD8+, and CD4+/ CD8+) and NK cell(CD161+) in the spleen were analyzed by flow cytometry. The PIS scores were significantly lower in the T1,T2,and T3 groups than those in the NS group. The spleen index and splenocyte proliferation induced by ConA were significantly suppressed in the T1 group,and the phenotypes of T lymphocyte subsets were significantly changed,but no significant difference was found in the T2 and T3 groups compared with the NS group. There were no differences in NK cell activity in the 3 tramadol groups from the control group. Intrathecal pumping tramadol has significantly antinociceptive effect. Intrathecal pumping higher dosage tramadol (50microg/h) suppresses T lymphocyte proliferation and alteres T lymphocyte subset phenotype but does not affect NK cell activity. General analgesic dosage tramadol (25 and 12.5 microg/h) has no effect on the immune function.


Hepatic fat and glucose tolerance in women with recent gestational diabetes.
Women with a history of gestational diabetes mellitus (GDM) have an elevated risk of ultimately developing pre-diabetes and diabetes later in life. They also have an increased prevalence of fatty liver, but recent studies have reported conflicting findings on whether hepatic fat affects their risk of pre-diabetes/diabetes. Thus, we sought to evaluate the associations of liver fat with glucose homeostasis and determinants thereof in women with and without recent gestational dysglycemia. Two hundred and fifty-seven women underwent an antepartum oral glucose tolerance test (OGTT), which diagnosed 97 with GDM, 40 with gestational impaired glucose tolerance (GIGT), and 120 with normal glucose tolerance (NGT). At a mean of 4.8 years post partum, they underwent an OGTT (which revealed that 52 had progressed to pre-diabetes/diabetes) and hepatic ultrasound, on which liver fat was graded as none (n=164), mild (n=66), or moderate (n=27). Liver fat was more prevalent in women with previous GDM than in those with GIGT or NGT (p=0.009) and in women with current pre-diabetes/diabetes than in those without (p=0.0003). As the severity of liver fat increased, there was a progressive worsening of insulin sensitivity and beta-cell function, coupled with rising fasting and 2-hour glucose (all p<0.0001). On multiple linear regression analyses, moderate liver fat was independently associated with lower insulin sensitivity (p=0.0002) and higher 2-hour glucose (p=0.009). Moreover, moderate liver fat emerged as an independent predictor of pre-diabetes/diabetes (OR=3.66, 95% CI 1.1 to 12.5). The higher prevalence of liver fat in women with previous GDM is associated with their increased risk of pre-diabetes/diabetes.


Miller Fisher Syndrome Triggered by Infections: A Review of the Literature and a Case Report.
We reported a case of Miller Fisher syndrome following a breakthrough varicella zoster virus infection in an otherwise healthy 6-year-old male. The objective of this review was to summarize the infectious etiologic agents known to trigger Miller Fisher syndrome. Review of the literature on infections associated with Miller Fisher syndrome. We identified 762 studies after duplicates were removed. Titles, abstracts, and full texts were screened. Finally, 37 studies were included in qualitative synthesis after citations and reference list were checked. The age range of cases reported was 0-78 years, and male sex was predominant in studies where these parameters were reported. The most common causative agent was Campylobacter jejuni followed by Haemophilus influenzae. Our review highlights the importance of recognizing the infections triggering Miller Fisher syndrome. We also present a unique case of Miller Fisher syndrome associated with breakthrough varicella zoster virus infection. Preventive policies may consider population immunization for certain causative agents.


Marital and Parent-Child Relationships during Treatment for Adolescent Depression: Child-Driven and Bidirectional Effects.
Adolescent depression can be a stressor for parents and families. This study evaluated how treating adolescent depression affects marital and parent-child relationships. We examined whether marital adjustment and parent-child conflict improved over the course of active treatment of depressed adolescents (36-week visit) and long-term follow-up (one year after discontinuation of treatment) in a sample of 322 clinically depressed youth participating in the Treatment for Adolescents with Depression Study (TADS). We also explored the bidirectional influences of adolescent depression and family relationships. Results indicated that marital adjustment was stable during active treatment but declined during long-term follow up. A structural equation model (SEM) examining the bidirectional relation between adolescent depression and marital adjustment indicated that higher adolescent depression at the conclusion of maintenance treatment (24-week visit) predicted a deterioration of marital adjustment at the end of active treatment (36-week visit). Parent-child conflict was unchanged during treatment and follow up. SEM analyses examining the bidirectional relationship between youth depression and parent-child conflict revealed that reduced depressive symptoms at the end of the active treatment period predicted improvement in parent-child conflict at subsequent time points. These findings suggest that youth depression and its treatment may influence long-term family functioning.


Therapeutic hepatocyte transplant for inherited metabolic disorders: functional considerations, recent outcomes and future prospects.
The applications, outcomes and future strategies of hepatocyte transplantation (HTx) as a corrective intervention for inherited metabolic disease (IMD) are described. An overview of HTx in IMDs, as well as preclinical evaluations in rodent and other mammalian models, is summarized. Current treatments for IMDs are highlighted, along with short- and long-term outcomes and the potential for HTx to supplement or supplant these treatments. Finally, the advantages and disadvantages of HTx are presented, highlighted by long-term challenges with interorgan engraftment and expansion of transplanted cells, in addition to the future prospects of stem cell transplants. At present, the utility of HTx is represented by the potential to bridge patients with life-threatening liver disease to organ transplantation, especially as an adjuvant intervention where severe organ shortages continue to pose challenges.


Peripheral biomarkers and illness activity in bipolar disorder.
Recent evidence suggests that peripheral markers related to oxidative stress, inflammation and neurotrophins may be altered during mood episodes in bipolar disorder. These can be seen as proxies of peripheral toxicity or markers of illness activity. Here we report an en bloc assessment of a set of previously described biomarkers in different mood states (n = 60) as well as in healthy subjects (n = 80). To make the point that these are ominous changes, we obtained the same measures from a group of septic patients (n = 15) as a "positive" control group. In this sample, we measured serum levels of brain derived neurotrophic factor, neurotrophin 3, tumor necrosis factor α, interleukin 6, interleukin 10, total reactive antioxidant potential, thiobarbituric acid reactive substances and protein carbonyl content. Several of the markers discriminated between the bipolar and control groups, especially when patients were in acute episodes. In some cases, toxicity was as high in bipolar disorder as that seen in patients with sepsis. We believe these findings highlight the potential of using biomarkers to assess illness activity in bipolar disorder.


ASSOCIATION OF NESFATIN-1 AND INSULIN RESISTANCE IN OBESE ADOLESCENTS OF IRAQ POPULATION.
Nesfatin-1 reduces body weight and the intake of food, it is also tangled in setting insulin release. This study aims at comparing the levels of serum of Nesfatin-1 with the insulin resistance in obese adolescent of iraqi population with other nations around the world predicating development of diabetes mellitus later. 90 participants were needed for this cross-sectional study, including 30 control participants (17 men and 13 women) and 60 obese adolescents (36 men and 24 women). Serum glucose, insulin, and glycated hemoglobin in starved participants were estimated, using an ELISA kit, the serum level of Nesfatin-1 was measured, and insulin resistance was calculated. Obese adolescents aged 12 to 18 and the control group, who were between 13 and 18 years old. The level of nesfatin-1 was significantly lower in the group of obese adolescents than in the controls. The ranges of Nesfatin-1 were (1.22±0.39 n/ml vs 2.54±0.64 n/m P = 0.001). In the control and obese groups respectively. In comparison to the results of the non-obese adolescent group, the obese group has significantly lower insulin sensitivity. Serum Nesfatin-1 is negatively associated with insulin sensitivity, lipid profile, and body mass index. In general, our study revealed that there is no effect of food culture and eating intake on the role of Nesfatin -1 inducing obesity.


Low efficacy of vaccination against serogroup B meningococci in patients with atypical hemolytic uremic syndrome.
The C5 complement inhibitor eculizumab is first-line treatment in atypical hemolytic uremic syndrome (aHUS) going along with a highly increased risk of meningococcal infections. Serogroup B meningococci (MenB) are the most frequently encountered cause for meningococcal infections in Europe. Efficacy of the protein-based MenB-vaccine Bexsero in aHUS has not been determined and testing is only possible in patients off-treatment with eculizumab as a human complement source is required. Patients with aHUS were vaccinated with two doses of the protein-based MenB-vaccine Bexsero. Serum bactericidal antibody (SBA) titers against factor H binding protein (fHbp) of MenB were determined in 14 patients with aHUS off-treatment with eculizumab. Only 50% of patients showed protective human serum bactericidal antibody (hSBA) titers (≥1:4) against MenB following two vaccinations. Bactericidal antibody titers were relatively low (≤1:8) in three of seven patients with protective titers. While 71% of patients were on immunosuppressive treatment for either thrombotic microangiopathy or renal transplantation at either first or second vaccination, all four patients not receiving any immunosuppressive treatment showed protective bactericidal antibody response. Time between second vaccination and titer measurement was not significantly different between patients with protective titers compared with those with non-protective titers, while time between first and second vaccination was significantly longer in patients with protective titers going along with a tendency for reduction in immunosuppressive treatment. Efficacy of vaccination against MenB is insufficient in patients with aHUS. Response to vaccination seems to be hampered by immunosuppression. Therefore, implementation of adequate antibiotic prophylaxis seems pivotal.


Immunostaining of Biocytin-filled and Processed Sections for Neurochemical Markers.
Electrophysiological recordings of cells using the patch clamp technique have allowed for the identification of different neuronal types based on firing patterns. The inclusion of biocytin/neurobiotin in the recording electrode permits post-hoc recovery of morphological details, which are necessary to determine the dendritic arborization and the regions targeted by the axons of the recorded neurons. However, given the presence of morphologically similar neurons with distinct neurochemical identities and functions, immunohistochemical staining for cell-type-specific proteins is essential to definitively identify neurons. To maintain network connectivity, brain sections for physiological recordings are prepared at a thickness of 300 µm or greater. However, this thickness often hinders immunohistological postprocessing due to issues with antibody penetration, necessitating the resectioning of the tissue. Resectioning of slices is a challenging art, often resulting in the loss of tissue and morphology of the cells from which electrophysiological data was obtained, rendering the data unusable. Since recovery of morphology would limit data loss and guide in the selection of neuronal markers, we have adopted a strategy of recovering cell morphology first, followed by secondary immunostaining. We introduce a practical approach to biocytin filling during physiological recordings and subsequent serial immunostaining for the recovery of morphology, followed by the restaining of sections to determine the neurochemical identity. We report that sections that were filled with biocytin, fixed with paraformaldehyde (PFA), stained, and coverslipped can be removed and restained with a second primary antibody days later. This restaining involves the removal of the coverslip, the washing of sections in a buffer solution, and the incubation of primary and secondary antibodies to reveal the neurochemical identity. The method is advantageous for eliminating data loss due to an inability to recover morphology and for narrowing down the neurochemical markers to be tested based on morphology.


Arabidopsis lyrata small RNAs: transient MIRNA and small interfering RNA loci within the Arabidopsis genus.
Twenty-one-nucleotide microRNAs (miRNAs) and 24-nucleotide Pol IV-dependent small interfering RNAs (p4-siRNAs) are the most abundant types of small RNAs in angiosperms. Some miRNAs are well conserved among different plant lineages, whereas others are less conserved, and it is not clear whether less-conserved miRNAs have the same functionality as the well conserved ones. p4-siRNAs are broadly produced in the Arabidopsis genome, sometimes from active hot spot loci, but it is unknown whether individual p4-siRNA hot spots are retained as hot spots between plant species. In this study, we compare small RNAs in two closely related species (Arabidopsis thaliana and Arabidopsis lyrata) and find that less-conserved miRNAs have high rates of divergence in MIRNA hairpin structures, mature miRNA sequences, and target-complementary sites in the other species. The fidelity of miRNA biogenesis from many less-conserved MIRNA hairpins frequently deteriorates in the sister species relative to the species of first discovery. We also observe that p4-siRNA occupied loci have a slight tendency to be retained as p4-siRNA loci between species, but the most active A. lyrata p4-siRNA hot spots are generally not syntenic to the most active p4-siRNA hot spots of A. thaliana. Altogether, our findings indicate that many MIRNAs and most p4-siRNA hot spots are rapidly changing and evolutionarily transient within the Arabidopsis genus.


Ictal-Interictal Continuum: When to Worry About the Continuous Electroencephalography Pattern.
Continuous electroencephalography (cEEG) monitoring is an invaluable tool in the evaluation of encephalopathy and coma in critically ill patients. Marked increases in cEEG monitoring, coinciding with several societal guideline statements in the last decade, have allowed earlier detection and treatment of clearly harmful patterns, including nonconvulsive seizures (NCSz) and nonconvulsive status epilepticus (NCSE). However, it has also unmasked a range of EEG patterns of less clear clinical significance, with some more "malignant" than others given their potential association with increased neuronal stress and secondary brain injury. These patterns lay on a spectrum often referred to as the ictal-interictal continuum (IIC). To date, no definitive guidelines exist for the management of these potentially harmful EEG patterns, thus presenting a clinical dilemma for critical care physicians. Here, we review the various IIC patterns, their associated features, seizure risk, and outcomes and also propose a clinical approach to management based on the available data and expert opinion.


Case: Spontaneous regression of post-radical prostatectomy prostate-specific antigen elevation without adjuvant therapy in a patient with lymph node metastasis.
Prostate cancer remains the most frequently diagnosed cancer among men. The combination of clinical stage, serum prostate-specific antigen (PSA), and Gleason score (biopsy) assists in predictive assessment of pathological stage and prognosis. Furthermore, pathological criteria, including Gleason score, surgical margin status, extracapsular extension, seminal vesicle invasion, and lymph node involvement, provide prognostication in patients undergoing radical prostatectomy (RP). In this paper, we present a case of a patient with high-risk prostate cancer with persistent PSA elevation post-RP who experiences a complete regression of PSA without any adjuvant therapy. To the authors' knowledge, such a finding has not been described in the literature previously.


Somatostatinoma of the minor papilla treated by local excision in a patient with neurofibromatosis type 1.
Somatostatinoma arising from the minor papilla in a patient with neurofibromatosis type 1 (NF1) is a known but very rare condition, which may cause non-specific symptoms and can present because of its mass effect. A fifty-year-old female presenting with ongoing non-specific abdominal pain for a few months duration was found to have a mass involving the minor papilla. She had a history of NF1 but was otherwise well. Magnetic resonance imaging showed a dilated pancreatic duct and the finding of pancreatic divisum. The lesion was (18)fluorine-fluoro-2-deoxyglucose positron emission tomography/computed tomography and (68)gallium (Ga) DOTATATE negative. Endoscopic ultrasound revealed a 1.7 cm lesion confined to the minor ampulla. Endoscopic retrograde pancreatography attempts with biopsy and endoscopic ultrasound fine needle aspiration biopsy were inconclusive and resulted in mild pancreatitis on two occasions. Open local excision of the minor papilla was undertaken without complications. Histology confirmed a completely excised grade 1 neuroendocrine tumor with intense diffuse somatostatin staining. Somatostatinoma of the minor papilla is a rare tumor that most commonly occurs in the setting of NF1 and may be amenable to local excision.


Veins with saccular dilatations in gastric mucosa of the rat.
It is well known that blood from the gastric mucosa of the rat is drained by collecting veins (venules). The aim of this study was to describe hitherto unrecognized saccular dilatations connected with these vessels. Rats received atropine or papaverine l h before ligation of the portal vein, Stomachs fixed in formaldehyde were prepared in toto after clearing in methyl salicylate or processed by standard histological technique. A single stomach contained about 1000 connecting veins localized exclusively in the oxyntic mucosa. After administration of relaxing agents and portal vein ligation the collecting veins were enlarged and in 80 percent of them one to three sacculi filled with blood could be seen. Histological observations shown that collecting veins empty into veins running between lamina muscularis and lamina propria mucosae. Sacculi were partially separated from the lumen of the collecting vein by a tissue band. In view of the relaxing effect evoked by atropine the veins and their sacculi appear to be under vagal control. Conceivably, their alternate expansion and collapse could facilitate movement of glandular content to the surface of the stomach and/or movement of interstitial fluid between cells.


Twin specific risk factors in primary school achievements.
The main aim of this study was to examine twin specific risk factors that influence educational achievement in primary school. We included prenatal factors that are not unique to twins, except for zygosity, but show a higher prevalence in twins than in singletons. In addition, educational achievement was compared between twins and their nontwin siblings in a within-family design. Data were obtained from parents and teachers of approximately 10,000 twins and their nontwin siblings registered with the Netherlands Twin Register. Teachers rated the proficiency of the children on arithmetic, language, reading, and physical education, and reported a national educational achievement test score (CITO). Structural equation modeling showed that gestational age, birth weight, and sex were significant predictors of educational achievement, even after correction for socioeconomic status. Mode of delivery and zygosity did not have an effect, while parental age only influenced arithmetic. Mode of conception, incubator time, and birth complications negatively affected achievement in physical education. The comparison of educational achievement of twins and singletons showed significantly lower ratings on arithmetic, reading, and language in twins, compared to their older siblings, but not compared to their younger siblings. Low gestational age and low birth weight were the most important risk factors for lower educational achievement of twins in primary school. It seems that the differences observed between twins and their nontwin siblings in educational achievement can largely be explained by birth order within the family.


Accurate and sensitive single-cell-level detection of copy number variations by micro-channel multiple displacement amplification (μcMDA).
Whole genome amplification (WGA) has laid the foundation for investigating complex genomic alteration with single-cell or even single-molecule resolution. Coupled with sequencing-based copy number variation (CNV) analysis, it promotes understanding of the nature of commonly existing genetic heterogeneity by constructing the sequencing profiles for every single cell. However, prevailing methods only provide insights into limited aspects due to their intrinsic technical challenges. Their output data, as a result, fails to render comprehensive information (which is) concerned. Here, we describe the CNV detection analysis based on micro-channel multiple displacement amplification (μcMDA), a protocol able to provide optimized amplification uniformity while inheriting the advantages of MDA chemistry. We demonstrate the analysis of both the normal diploid YH-1 cell line and the aneuploid K562 cancer cell line. In the detection of simulated CNVs ranging from 300 kb to 2 Mb, μcMDA can respectively increase the detection rates of copy number loss and gain by 28.8% and 40.2% on average, using only 0.2× sequencing data. When detecting the inherent CNVs in tumor cells, the resolution of CNV recognition can be improved to 250 kb. Starting from either superabundant template copies or minute single-cell-level input, this easily accessible approach is capable of providing quantitatively reliable coverage as well as more robust GC-content regression for CNV detection.


Cardiac rehabilitation referral and attendance: not one and the same.
Despite empirical evidence that cardiac rehabilitation programs can play a significant role in enhancing recovery following a primary cardiac event and in enacting secondary prevention measures, attendance rates remain remarkably low. Referral and attendance at cardiac rehabilitation programs are not one and the same. Recognizing this, issues related to the referral of eligible patients to cardiac rehabilitation and factors that affect patients' decisions regarding attendance must be identified and addressed. This article presents an overview of the potential benefits of cardiac rehabilitation programs, describes salient issues related to referral and attendance, and identifies directions for future research.


Cigarette smoke effects on innate immune mechanisms in the nasal mucosa. Potential effects on the microbiome.
It is well established that exposure to cigarette smoke (CS), through active smoking and through exposure to secondhand smoke, has immunosuppressive effects, yet how this might affect the microbiome is not known. In this manuscript we focus on the effects of CS on innate host defense response, with particular emphasis on the role of epithelial cells and mucosal immune responses in the nose and the potential effects on the microbiome. The studies described here briefly summarize the effects of CS on specific innate immune cells, such as neutrophils, macrophages/monocytes, natural killer cells, and dendritic cells. A detailed description of how CS affects epithelial cells and why we consider this to be a central defect in the overall immunosuppressive effects of CS in the lung is provided. We summarize data on the role of the "epimmunome" in the context of CS exposure, including the effects on soluble mediator production, such as cytokines, chemokines, and antimicrobial defense mediators. Separate emphasis is put on the expression of ligands on epithelial cells, which directly interact with receptors on immune cells, and the effects of CS on these interactions. We introduce the nose and nasal mucosa as a model to study the effects of CS exposure on host defense responses and changes in the microbiome in humans in vivo. Understanding the dynamics of a healthy microbiome and how CS affects this balance is important to uncovering the mechanisms of CS-induced disease.


Case Report: Acute Onset Fear of Falling and Treatment With "Cognitive Physical Therapy".
Fear of falling (FoF) is prevalent in older adults, especially those with previous falls, and typically starts insidiously. We present a 78-year-old woman with an abrupt onset FoF and no history of falls, balance problems, vertigo, oscillopsia, psychiatric or psychological issues to account for this. These cognitive changes led to a behavioural alteration of her gait that became slow and wide-based, with her gaze fixed on the floor. She began a tailored program of "Cognitive Physical Therapy (CPT)" combining cognitive behavioural therapy (CBT) and physical rehabilitation. 1 month later her 6 m walk time and steps were reduced by a 25 and 35%, respectively, and the stride length increased by 34%, with further improvement 2 months later. We postulate that the abrupt onset of symptoms triggered a central shift toward postural hypervigilance and anxiety, suppression of anticipatory (feed forward) postural adjustments (APA) leading to FoF. CPT improved objective gait parameters related to FoF and reduced postural anxiety suggesting that early diagnosis and prompt treatment may avoid chronic symptoms and social isolation.


Elevated risk of tobacco dependence among offspring of mothers who smoked during pregnancy: a 30-year prospective study.
The authors' goal was to investigate whether maternal smoking during pregnancy is associated with an increased risk of nicotine dependence among adult offspring. Prospective data from two samples of offspring in the National Collaborative Perinatal Project, a long-term prospective investigation from pregnancy through adulthood, were combined (N=1,248). Maternal smoking during pregnancy was assessed during each prenatal visit. Offspring smoking behavior and lifetime risk of nicotine dependence were obtained by structured interview with the Diagnostic Interview Schedule; the mean age of the offspring at the time of interview was 29 years. Offspring whose mothers reported smoking a pack or more of cigarettes during their pregnancy were significantly more likely to meet DSM criteria for lifetime tobacco dependence than offspring of mothers who reported that they never smoked during pregnancy. The odds of progressing from smoking to nicotine dependence were almost twice as great for offspring whose mothers smoked heavily during pregnancy. These significant differences remained after adjustments for participants' gender and age and maternal socioeconomic status and age at pregnancy. Results were comparable for men and women. The findings were specific for tobacco dependence; odds of marijuana dependence were not significantly elevated among the offspring of tobacco smokers. Offspring of mothers who smoked a pack or more of cigarettes during pregnancy are at elevated risk of developing nicotine dependence but not marijuana dependence as adults. Maternal smoking during pregnancy is a risk factor for subsequent nicotine dependence among offspring.


Microscopic characteristics of genital end bulbs in the penis of bulls.
Light microscopic sections of Epon-embedded bull penis were examined for nerve endings. Tissue was taken from the dorsal midline of the glans penis and from the free portion of the penis in 6 mature bulls. Genital end bulbs were identified in both regions of the penis and were located from 1 to 500 micron beneath the epithelium, with most end bulbs concentrated next to the epithelium in the glans penis. Occasionally, end bulbs were found within nerve trunks. Other encapsulated endings were not seen. Ultrastructural correlation of the light and electron microscopic appearance of spherical end bulbs and elongated end bulbs indicated that their structure was identical. Two to 6 neurites filled with mitochondria were surrounded by several layers of thin cytoplasmic lamellae. The lamellae were characterized by pinocytotic vesicles, microtubules, and a scant basal lamina. A capsule of differing thickness enclosed the end bulbs. Fewer capsular layers surrounded more superficially located end bulbs. Near the epithelium, there were gaps in the capsule. Nonmyelinated fibers were seen within end bulbs and between end bulbs and the epithelium.


Molecular analyses of Fusarium isolates recovered from a cluster of invasive mold infections in a Brazilian hospital.
Invasive fusariosis (IF) is a rare but often fatal fungal infection in immunosuppressed patients. In 2007, cases of IF above the expected epidemiologic baseline were detected in the hematology ward of a hospital in Rio de Janeiro, Brazil. Possible sources of infection were investigated by performing environmental sampling and patient isolate collection, followed by molecular typing. Isolates from dermatology patients with superficial fusariosis were included in the study for comparison to molecular types found in the community. Environmental sampling focused on water-related sources in and around the hematology ward. Initially, we characterized 166 clinical and environmental isolates using the Fusarium translation elongation factor 1α (EF-1α) genetic locus. Isolates included 68 collected from water-related sources in the hospital environment, 55 from 18 hematology patients, and 43 from the skin/nails of 40 outpatients seen at the hospital dermatology clinic. Multi-locus sequence typing was performed on Fusarium solani species complex (FSSC) species 1 and 2 isolates to investigate their relatedness further. Most of the hematology samples were FSSC species 2, with species type FSSC 2-d the most commonly isolated from these patients. Most of the outpatient dermatology samples were also FSSC 2, with type 2-d again predominating. In contrast, environmental isolates from water sources were mostly Fusarium oxysporum species complex (FOSC) and those from air samples mostly Fusarium incarnatum-equiseti species complex (FIESC). A third of the environmental samples were FSSC, with species types FSSC 1-a and FSSC 1-b predominating. Fusarium isolate species types from hematology patient infections were highly similar to those recovered from dermatology patients in the community. Four species types (FSSC 1-a, 1-b, 2-d and 2-f) were shared between hematology patients and the environment. Limitations in environmental sampling do not allow for nosocomial sources of infection to be ruled out. Future studies will focus on environmental factors that may have influenced the prevalence of FSSC fusariosis in this hematology ward.


Induction of thyroid neoplasm following plant medicine marine algae (sargassum): a rare case and review of the literature.
In this study induction of neoplasm in thyroid gland of one postoperative patient with breast cancer was conducted by marine algae (also seaweed, sargassum), which is presented here. A 41-year-old women was diagnosed as her right breast cancer complicated with lymph node metastasis in her right axilla on February, 1999. In June 19, 1999 she was given the combination chemotherapy of vincristine, cyclophosphamide, 5-Fluorouracil and cinobufacini drugs due to two lymph nodes on her right superclavicular following radical mastectomy. During chemotherapy she was also taken the adjuvant treatment of traditional medicine. Traditional medicine consisted of seaweed plant drugs (containing iodine 362,400 ug/kg). As to intermittent maintance treatment the total dosage of seaweed herb was at least exceeded 500 gram. Induction of thyroid tumor (thumb size) was found in June, 2001. A thyroidectomy due to thyroma was successfully performed. Histologically there revealed thyroid tissue without the evidence of metastasis of breast cancer. She had a 5-year survivor. The data indicated oncogenic function of some traditional herbs, and further experience of traditional medicine in treating thyroid disease especially in thyroid cancer.


Practitioner review: psychological sequelae of head injury in children and adolescents.
Many children suffer an injury to the head at some time, but relatively few of these cause major problems. However, in a few cases the sequelae can be far reaching. This review considers how to evaluate the significance of a head injury. Factors to consider are (1) injury variables: cause, severity and type of injury; (2) child variables: premorbid functioning, age, and developmental level of the child both at injury and at assessment; and (3) the cognitive, behavioural, and emotional problems that may arise. Parental beliefs and knowledge about the injury as well as the overall effect of an injury on the family as a whole are also considered.


Biochemical markers of bone metabolism in children with Helicobacter pylori infection.
We investigated the biochemical markers of bone metabolism in children with Helicobacter pylori infection. Biochemical markers of bone metabolism and serum levels of vitamin B12, ferritin and estradiol were measured in 41 H. pylori-positive (+) children (23 girls, 18 boys; aged 11.8+/-3 years). Serum levels of intact parathyroid hormone, ss-collagen I carboxy terminal telopeptide, total alkaline phosphatase (ALP), bone-specific ALP, N-terminal cross-links of human procollagen type I, N-mid-osteocalcin, calcium, phosphate, ferritin, and estradiol did not differ significantly between H. pylori(+) and H. pylori negative (-) children. Vitamin B12 levels were significantly decreased in H. pylori(+) compared to H. pylori(-) children. H. pylori infection was not accompanied by significant changes in markers of bone metabolism in children, although vitamin B12 levels were decreased. Further studies are required to clarify whether H. pylori infection causes time-dependent changes in bone turnover markers during the long course of this inflammatory disease.


Type D Personality Predicts Poor Medication Adherence in Chinese Patients with Type 2 Diabetes Mellitus: A Six-Month Follow-Up Study.
Type D personality and medication nonadherence have been shown to be associated with poor health outcomes. Type D personality is associated with poor medication adherence in patients with coronary artery disease, myocardial infarction, and heart failure. However, the relationship between type D personality and medication adherence in patients with Type 2 Diabetes Mellitus (T2DM) remains unknown. This study aims to examine whether type D personality was associated with medication adherence in patients with T2DM. A follow-up study was conducted in general hospital of the People's Liberation Army in Beijing. 412 T2DM patients (205 females), who were recruited by circular systematic random sampling, provided demographic and baseline data about medical information and completed measures of Type D personality. Then, 330 patients went on to complete a self-report measure of medication adherence at the sixth month after baseline data collection. Chi-square test, t tests, and hierarchical multiple regression analyses were conducted, as needed. Patients with type D personality were significantly more likely to have poor medication adherence (p<0.001). Type D personality predicts poor medication adherence before and after controlling for covariates when it was analyzed as a categorical variable. However, the dimensional construct of type D personality was not associated with medication adherence when analyzed as a continuous variable. Although, as a dimensional construct, type D personality may not reflect the components of the personality associated with poor medication adherence in patients with T2DM, screening for type D personality may help to identify those who are at higher risk of poor medication adherence. Interventions, aiming to improve medication adherence, should be launched for these high-risk patients.


HIV-1 diagnosis using dried blood spots from patients in Kinshasa, DRC: a tool to detect misdiagnosis and achieve World Health Organization 2030 targets.
Currently, only 54% of the population of the Democratic Republic of the Congo (DRC) know their HIV status. The aim of this study was to detect HIV misdiagnosis from rapid diagnostic tests (RDT) and to evaluate serological immunoassays using dried blood spots (DBS) from patients in Kinshasa, DRC. Between 2016 and 2018, 365 DBS samples were collected from 363 individuals and shipped to Spain. The samples were from people with a new HIV positive (n = 123) or indeterminate (n = 23) result, known HIV-positive patients (n = 157), and a negative control group (n = 62). HIV serology was performed using Elecsys HIV combi PT (Roche), VIDAS HIV Duo Quick (BioMérieux), and Geenius (Bio-Rad). In addition, HIV RNA detection was performed in all samples using the COBAS AmpliPrep/COBAS Taqman HIV-1 Test 2.0 (Roche). Overall, 272 samples were found to be positive and 93 to be negative for HIV serology. The sensitivity was 100% for both Elecsys and VIDAS techniques, but specificity was slightly higher for the VIDAS test: 100% (96.1-100%) vs 98.9% (94.1-99.9%). Of the 23 indeterminate cases using RDT, only three cases were true-positives with a detectable viral load. Eleven samples out of the 280 classified as positive by RDT corresponded to nine patients who had received a false diagnosis of HIV through RDT (3.9%); six of them had been on antiretroviral therapy for at least 2 years. Elecsys HIV combi PT and VIDAS HIV Duo Quick immunoassays showed high sensitivity and specificity when using DBS. RDT-based serological diagnosis can lead to HIV misdiagnosis with personal and social consequences in sub-Saharan Africa.


Economics of end-of-life care in the intensive care unit.
End-of life care is in need of improvement, yet little is known about the effectiveness or cost of various end-of-life therapies. Economic analyses are used to help make decisions between two or more therapies when resources are constrained. In this chapter, we review the various types of economic analyses, the costs of dying, and how healthcare reform has impacted these costs. Finally, we discuss the unique issues associated with cost-effectiveness studies of palliative therapy, with emphasis on the problem of calculating a cost-effectiveness ratio when there is no good measurement for valuing the quality of death. It is likely that methods for conducting a cost-effectiveness analyses for end-of-life care will need to evolve or alternative strategies such as cost-benefit analysis or distributive justice will be needed to inform resource allocation decisions. As the national debate about healthcare costs, access, and quality continues, we will increasingly turn to economic analyses to help make resource allocation decisions. Cost-effectiveness analysis will continue to be the most popular form of economic analysis because it combines the results (effectiveness of treatment) with the costs of achieving the results. We must be aware of the limitations of cost-effectiveness analyses and the need for value judgments when using cost-effectiveness analyses to inform healthcare decisions.


Brain-penetrating nanoparticles improve paclitaxel efficacy in malignant glioma following local administration.
Poor drug distribution and short drug half-life within tumors strongly limit efficacy of chemotherapies in most cancers, including primary brain tumors. Local or targeted drug delivery via controlled-release polymers is a promising strategy to treat infiltrative brain tumors, which cannot be completely removed surgically. However, drug penetration is limited with conventional local therapies since small-molecule drugs often enter the first cell they encounter and travel only short distances from the site of administration. Nanoparticles that avoid adhesive interactions with the tumor extracellular matrix may improve drug distribution and sustain drug release when applied to the tumor area. We have previously shown model polystyrene nanoparticles up to 114 nm in diameter were able to rapidly diffuse in normal brain tissue, but only if coated with an exceptionally dense layer of poly(ethylene glycol) (PEG) to reduce adhesive interactions. Here, we demonstrate that paclitaxel (PTX)-loaded, poly(lactic-co-glycolic acid) (PLGA)-co-PEG block copolymer nanoparticles with an average diameter of 70 nm were able to diffuse 100-fold faster than similarly sized PTX-loaded PLGA particles (without PEG coatings). Densely PEGylated PTX-loaded nanoparticles significantly delayed tumor growth following local administration to established brain tumors, as compared to PTX-loaded PLGA nanoparticles or unencapsulated PTX. Delayed tumor growth combined with enhanced distribution of drug-loaded PLGA-PEG nanoparticles to the tumor infiltrative front demonstrates that particle penetration within the brain tumor parenchyma improves therapeutic efficacy. The use of drug-loaded brain-penetrating nanoparticles is a promising approach to achieve sustained and more uniform drug delivery to treat aggressive gliomas and potentially other brain disorders.


Human interferons protect plants from virus infection.
Unfractionated human leukocyte interferon, as well as highly purified subspecies of this interferon, and a purified recombinant of human leukocyte interferon produced in bacteria are active in suppressing multiplicability of tobacco mosaic virus in tobacco leaf discs. Human fibroblast interferon exhibits diverse levels of antiviral activity against tobacco mosaic virus but becomes as active as human leukocyte interferon upon incubation with glycosidases. The effect of interferon is reversible; normal multiplication of tobacco mosaic virus resumes upon removal of interferon.


Coxsackievirus expression of the murine secretory protein interleukin-4 induces increased synthesis of immunoglobulin G1 in mice.
We cloned the sequence encoding murine interleukin-4 (mIL-4), including the secretory signal, into the genome of CVB3/0, an artificially attenuated strain of coxsackievirus B3, at the junction of the capsid protein 1D and the viral protease 2Apro. Two strains of chimeric CVB3 were constructed using, in one case, identical sequences to encode 2Apro cleavage sites (CVB3/0-mIL4/47) on either side of the inserted coding sequence and, in the other case, nonidentical sequences that varied at the nucleotide level without changing the amino acid sequences (CVB3-PL2-mIL4/46). Transfection of HeLa cells yielded progeny viruses that replicated with rates similar to that of the parental CVB3/0 strain, although yields of mIL-4-expressing strains were approximately 10-fold lower than those of the parental virus. Western blot analysis of viral proteins isolated from HeLa cells inoculated with either strain of chimeric virus demonstrated that the chimeric viruses synthesized capsid protein 1D at approximately twofold-higher levels than the parental virus. mIL-4 protein was detected by enzyme-linked immunosorbent assay (ELISA) in HeLa cells inoculated with either strain of chimeric virus. Lysates of HeLa cells inoculated with either chimeric virus induced the proliferation of the mIL-4-requiring murine MC-9 cell line, demonstrating biological activity of the CVB3-expressed mIL-4. Reverse transcription (RT)-PCR analysis of viral RNA derived from sequential passaging of CVB3/0-mIL4/47 in HeLa cells demonstrated deletion of the mIL-4 coding sequence occurring by the fourth passage, while similar analysis of CVB3-PL2-mIL4/46 RNA demonstrated detection of the mIL-4 coding sequence in the virus population through 10 generations in HeLa cells. mIL-4 protein levels determined by ELISA were consistent with the stability and loss data determined by RT-PCR analysis of the passaged viral genomes. Studies of insert stability of CVB3-PL2-mIL4/46 during replication in mice showed the presence of the viral mIL-4 insert in pancreas, heart, and liver at 14 days postinfection. Comparison of the murine antibody responses to CVB3-PL2-mIL4/46 and the parental CVB3/0 strain demonstrated an increased level of CVB3-binding serum immunoglobulin G1 in mice inoculated with CVB3-PL2-mIL4/46.


The clinical implications of thrombocytopenia in adults with severe falciparum malaria: a retrospective analysis.
Thrombocytopenia is a common finding in adults with severe falciparum malaria, but its clinical and prognostic utility is incompletely defined. Clinical and laboratory data from 647 adults with severe falciparum malaria were analysed retrospectively to determine the relationship between a patient's platelet count on admission to hospital and their subsequent clinical course. On admission, 614 patients (94.9%) were thrombocytopenic (platelet count <150 × 10(9)/L) and 328 (50.7%) had a platelet count <50 × 10(9)/L. The admission platelet count was inversely correlated with parasite biomass (estimated from plasma PfHRP2 concentrations, rs = -0.28, P = 0.003), the degree of microvascular sequestration (measured with orthogonal polarizing spectral imaging, rs = -0.31, P = 0.001) and disease severity (the number of World Health Organization severity criteria satisfied by the patient, rs = -0.21, P <0.001). Platelet counts were lower on admission in the patients who died (median: 30 (interquartile range 22 to 52) × 10(9)/L versus 50 (34 to 78) × 10(9)/L in survivors; P <0.001), but did not predict outcome independently from other established laboratory and clinical prognostic indices. The 39 patients (6%) with profound thrombocytopenia (platelet count <20 × 10(9)/L) were more likely to die (odds ratio: 5.00, 95% confidence interval: 2.56 to 9.75) than patients with higher platelet counts, but these high-risk patients could be identified more rapidly with simple bedside clinical assessment. The admission platelet count did not reliably identify the 50 patients (7.7%) with major bleeding during the study. Thrombocytopenia is a marker of disease severity in adults with falciparum malaria, but has limited utility in prognostication, triage and management.


Analysis of Malassezia microbiota in healthy superficial human skin and in psoriatic lesions by multiplex real-time PCR.
Yeasts from the genus Malassezia are members of the normal biota of human skin, and may play a role in dermatopathology. Our previous study of the fungal microbiota from healthy subjects and from patients with psoriasis using clone library analysis revealed the presence of five Malassezia species and four uncharacterized phylotypes. We now compared the Malassezia microbiota from six healthy body locations and two psoriatic lesions, and evaluated its stability over time using multiplex real-time PCR. Samples from each body location were obtained monthly, for 4 months. Dual-labeled probes were designed to recognize four Malassezia sp. and two uncharacterized groups, and a genus-specific probe was also developed. A good correspondence was obtained between real-time PCR data and clone library analyses. Malassezia restricta was the most abundant species in the majority of samples, and high amounts of Malassezia globosa were also detected. The uncharacterized phylotype 1 was usually detected in lower proportions, nevertheless it was present in most samples. The microbiota was host-specific and relatively stable over time. In accordance with our previous observations, no significant dichotomy between samples from healthy skin and from psoriatic lesions was found; the samples clustered according to the subject, rather than health status.


Major abdominal bleeding in chronic pancreatitis.
This case report concerns a patient with chronic pancreatitis which led to extensive retroperitoneal haemorrhage from a rupture of the abdominal aorta. The rarity of this complication is emphasized, but other reported instances of bleeding in association with chronic pancreatitis are commented upon.


Glucocorticoid resistance.
Changes in glucocorticoid (GC) receptor sensitivity can be categorized in three different types. First, generalized GC resistance syndrome is a hereditary disease. Patients present with signs and symptoms of increased androgen and/or mineralocorticoid action, combined with biochemical hypercortisolism, but lack of cushingoid features. Second, at a tissue level, transient changes in GC sensitivity are present during disease. Transient changes in GC sensitivity of leukocytes during infectious diseases like sepsis have been found, but also acquired forms or GC resistance occur, in particular in some types of neoplasms, major depression, AIDS, and several autoimmune diseases. Third, at the level of the general population, the diversity in GC sensitivity has a wide interindividual variation which in part can be explained by genetic variation of the GC receptor gene. Several single nucleotide polymorphisms of the gene have been associated with changes in GC sensitivity and its clinical phenotype. In this chapter, four genetic variants are described of which two (rs6198 and rs6189/6190) are associated with a relative GC resistance and two (rs1695 and rs41423247) are associated with a relative GC hypersensitivity.


Landscape changes and livelihood outcomes in rural tea farming communities: A case study in Fuding City, Fujian Province, Southeast China.
Landscape changes driven by cash crop plantations have been prevalent in tropical and subtropical regions worldwide in recent decades. Investigating the landscape changes and concluding livelihood outcomes are fundamental to figure out the solutions for rural sustainability. This paper examined the landscape changes which was caused by land use changes in tea plantations as well as investigated the resultant livelihood impacts, based on a case study in Fuding City, Southeast China. A questionnaire survey of 114 rural households in four sampled villages was conducted. Results demonstrated that expansion and intensification of tea plantations were two major proximate causes of landscape changes in recent decade. Our survey indicated that some existing intensively-managed tea plantations had derived from intensification and expansion of tea plantations, respectively. We identified four underlying driving forces of landscape changes, including economic benefit, governmental policies, wildlife destruction on grain crops, and rural return migration. Our study confirmed that landscape changes have significant positive effects on farmers' livelihoods, including increasing employment and incomes, raising living standards, enhancing livelihood assets and livelihood sustainability. Especially, the aged rural populations could have a relatively decent living standard. Meanwhile, the excessive expansion of tea plantations may impair livelihood resilience. Lastly, three policy suggestions based on different time scales have been put forward to promote rural households' livelihood sustainability and resilience.


Only one of the charged amino acids located in membrane-spanning regions is important for the function of the Saccharomyces cerevisiae uracil permease.
The transport of uracil into the yeast Saccharomyces cerevisiae is mediated by uracil permease, a specific co-transporter encoded by the FUR4 gene. Uracil permease is a multispan membrane protein that is delivered to the plasma membrane via the secretory pathway. Experimental results led to the proposal of a two-dimensional model of the protein's topology. According to this model, the membrane domain of Fur4p contains three charged amino acid residues (Glu-243, Lys-272 and Glu-539) that are conserved in the members of the FUR family of yeast transporters. We have previously shown that a mis-sense mutation leading to the replacement of Lys-272 by Glu severely impairs the function of uracil permease. In the present paper, the role of the three charged residues present in the membrane-spanning regions of Fur4p was further investigated by using site-directed mutagenesis. The variant permeases were correctly targeted to the plasma membrane and their stabilities were similar to that of the wild-type permease. The effect of the mutations was studied by measuring the uptake constants for uracil on whole cells and equilibrium binding parameters on plasma membrane-enriched fractions. We found no evidence for ionic interaction between either of the glutamic residues in transmembrane segments 3 and 9 and the lysine residue in transmembrane segment 4. Of the three charged residues, only Lys-272 was important for the transport activity of the transporter. Its replacement by Ala, Glu or even Arg strongly impaired both the binding and the translocation of uracil.


EFFECT OF INHALED OXYGEN CONCENTRATION ON PULMONARY GAS EXCHANGE DURING OFF-PUMP CORONARY BYPASS GRAFTING.
Aim of study - supra-physiologic level of PaO2, securing oxygen reserves and preventing perioperative hypoxia, may offset the reduced oxygen delivery during cardiac surgery. However, high FiO2 will speed up gas absorption in low V/Q regions, promote atelectasis formation and increase pulmonary shunt fraction. PaO2/FiO2, P(a-Et)CO2 and PEtCO2/PaCO2 are the variables linked to CO2 and O2 exchange impairment. The aim of our study was to assess pulmonary gas exchange performance while ventilating patients with different FiO2 during OPCABG. The seventy patients were randomly equally distributed in two groups: H (High) and L (Low). The patients in the group H were ventilated with FiO2 0.8 and the patients in the group L _ with FiO2 0.5. PaO2/FiO2 ratio, P(a-Et)CO2 gradient and PEtCO2/PaCO2 ratio were checked at the start and the end points of operations. PaO2/FiO2 decreased, P(a-Et)CO2 increased and PaCO2/PEtCO2 decreased at the end of operations compared with the start values in both groups. PaO2/FiO2, P(a-Et)CO2 and PaCO2/PEtCO2 ware different between H and L groups. The difference became statistically significant at the end of operations. (PaO2/FiO2 326±65 vs 290±63 p=0.020; P(a-Et)CO2 5.7±2.3 mmHg vs 7.5±2.4 mmHg p=0.003; PaCO2/PEtCO2 0.84±0.05 vs 0.80±0.06 p=0.001). The groups were comparable according to the outcomes such as hemodynamic and laboratory data, duration of postoperative mechanical ventilation and ICU length of stay. FiO2 0.8 was associated with more derangements of pulmonary gas exchange compared with FiO2 0.5. Although FiO2 did not have an impact on the outcomes we studied, using FiO2 0.5 seems to be safer in patients undergoing OPCABG.


Osmotically regulated taurine content in rat renal inner medulla.
During antidiuresis renal medullary cells were previously found to accumulate large amounts of organic osmolytes, namely sorbitol, myo-inositol, glycerophosphorylcholine (GPC), and betaine. Large quantities of amino acids are also present in the renal medulla, but it has been questionable whether the levels of medullary amino acids are osmotically regulated. Therefore we directly measured 26 different amino acids, as well as sorbitol, myo-inositol, GPC, and betaine alone the corticomedullary axis of rats that were either salt loaded, after infusion of hypertonic NaCl solution, or were hydrated, after infusion of hypotonic NaCl solution. The amounts of sorbitol, myo-inositol, GPC, and betaine are greater in the inner medullas of salt-loaded rats compared with hydrated rats. In addition, the amount of taurine is much greater in the inner medullas of salt-loaded rats. Aspartic acid also increases in salt-loaded rats but to a lesser extent. There are substantial gradients of taurine, aspartic acid, and some of 24 other measured amino acids along the corticomedullary axis. However, taurine and aspartic acid are the only measured amino acids that increase significantly during salt loading.


Curcumin mitigates gentamicin induced-renal and cardiac toxicity via modulation of Keap1/Nrf2, NF-κB/iNOS and Bcl-2/BAX pathways.
Gentamicin (GEN) is an aminoglycoside antibiotic used to treat gram-negative bacterial infections. Our study aimed to explore curcumin's (CMN) protective role against GEN-induced renal and cardiac toxicity. Rats were randomly classified into 4 equal groups; Control (cont), GEN (100 mg/kg b.wt, i.p.) for seven days, CMN (200 mg/kg b.wt, orally) for 21 days, and CMN + GEN groups. GEN caused renal and cardiac dysfunctions; increased urea, creatinine, uric acid, cystatin C, CK-MB, LDH, and troponin I serum levels. MDA level was elevated significantly while activities of SOD, CAT, and GSH level were reduced significantly in renal and cardiac tissues. GEN-intoxicated rats showed up-regulation of NF-κB, IL-1β, Keap1, HMOX1, and BAX with down-regulation of Nrf2, and Bcl-2 mRNA expression in renal and cardiac tissues. Also, GEN-induced up-regulation of renal mRNA expression of KIM-1, NGAL, and intermediate filament proteins [desmin, nestin, and vimentin] as well cardiac gene expression of cMyBP-C and H-FABP. GEN-induced toxicity was significantly attenuated by CMN co-treatment as CMN improved renal and cardiac biomarkers, reduced oxidative stress and inflammatory response, and reversed alterations in mRNA expression of all tested renal and cardiac genes. These outcomes indicated that CMN could protect renal and cardiac tissues against GEN-induced oxidative stress, inflammation, and apoptosis.


Mitochondrial cytopathies.
Mitochondria are found in all nucleated human cells and perform a variety of essential functions, including the generation of cellular energy. Most of mitochondrial proteins are encoded by the nuclear DNA (nDNA) whereas a very small fraction is encoded by the mitochondrial DNA (mtDNA). Mutations in mtDNA or mitochondria-related nDNA genes can result in mitochondrial dysfunction which leads to a wide range of cellular perturbations including aberrant calcium homeostasis, excessive reactive oxygen species production, dysregulated apoptosis, and insufficient energy generation to meet the needs of various organs, particularly those with high energy demand. Impaired mitochondrial function in various tissues and organs results in the multi-organ manifestations of mitochondrial diseases including epilepsy, intellectual disability, skeletal and cardiac myopathies, hepatopathies, endocrinopathies, and nephropathies. Defects in nDNA genes can be inherited in an autosomal or X-linked manners, whereas, mtDNA is maternally inherited. Mitochondrial diseases can result from mutations of nDNA genes encoding subunits of the electron transport chain complexes or their assembly factors, proteins associated with the mitochondrial import or networking, mitochondrial translation factors, or proteins involved in mtDNA maintenance. MtDNA defects can be either point mutations or rearrangements. The diagnosis of mitochondrial disorders can be challenging in many cases and is based on clinical recognition, biochemical screening, histopathological studies, functional studies, and molecular genetic testing. Currently, there are no satisfactory therapies available for mitochondrial disorders that significantly alter the course of the disease. Therapeutic options include symptomatic treatment, cofactor supplementation, and exercise.


[Illustration and results of antineoplastic chronopharmacology in pulmonary tumors].
Reference is made to a series of cases of lung tumour treated with antiblastic drugs over long periods. This method gives the best results in terms of survival and tolerance. Encouraging results were also obtained with coadjuvant chronobiological corticoid management.


Improving Nutrition by Increasing Supplemental Nutrition Assistance Program Benefits.
The diets of Americans fall far short of recommended dietary guidelines, and those who live in low-income households have even poorer diets than higher-income households. Many low-income Americans rely on the Supplemental Nutrition Assistance Program (SNAP). The program's dual goals are to improve food security and nutrition. Among the possible strategies to address dietary shortfalls among low-income Americans is to increase the SNAP benefit. This article uses data from the random assignment evaluation of the Summer Electronic Benefit Transfer for Children demonstration to add new insights on the impact of SNAP on diet quality for households receiving SNAP who also received SNAP-like benefits through Summer Electronic Benefit Transfer for Children. Households received $60 each month per eligible school-aged child. The objective of the evaluation was to see if Summer Electronic Benefit Transfer for Children improved children's food security and nutrition. The evaluation surveyed these households to collect information about food expenditures, food security, and children's diets. For households receiving SNAP in sites that used the SNAP Electronic Benefit Transfer delivery system, the analysis showed increases in food expenditures and decreases in levels of food insecurity. The analysis also indicates improvements in dietary quality among school-aged children, but the impacts were modest.


Coordination of Slow Waves With Sleep Spindles Predicts Sleep-Dependent Memory Consolidation in Schizophrenia.
Schizophrenia patients have correlated deficits in sleep spindle density and sleep-dependent memory consolidation. In addition to spindle density, memory consolidation is thought to rely on the precise temporal coordination of spindles with slow waves (SWs). We investigated whether this coordination is intact in schizophrenia and its relation to motor procedural memory consolidation. Twenty-one chronic medicated schizophrenia patients and 17 demographically matched healthy controls underwent two nights of polysomnography, with training on the finger tapping motor sequence task (MST) on the second night and testing the following morning. We detected SWs (0.5-4 Hz) and spindles during non-rapid eye movement (NREM) sleep. We measured SW-spindle phase-amplitude coupling and its relation with overnight improvement in MST performance. Patients did not differ from controls in the timing of SW-spindle coupling. In both the groups, spindles peaked during the SW upstate. For patients alone, the later in the SW upstate that spindles peaked and the more reliable this phase relationship, the greater the overnight MST improvement. Regression models that included both spindle density and SW-spindle coordination predicted overnight improvement significantly better than either parameter alone, suggesting that both contribute to memory consolidation. Schizophrenia patients show intact spindle-SW temporal coordination, and these timing relationships, together with spindle density, predict sleep-dependent memory consolidation. These relations were seen only in patients suggesting that their memory is more dependent on optimal spindle-SW timing, possibly due to reduced spindle density. Interventions to improve memory may need to increase spindle density while preserving or enhancing the coordination of NREM oscillations.