Radiographic measures of knee alignment in patients with varus gonarthrosis: effect of weightbearing status and associations with dynamic joint load.
Radiographic measures of lower limb malalignment are used to indicate abnormal loading of the knee and to plan corrective procedures. Weightbearing status during hip-to-ankle radiographs will significantly affect malalignment measures; malalignment in single-limb standing will be most highly correlated to the external knee adduction moment during gait, a proposed dynamic measure of functional knee joint load. Controlled laboratory study. Mechanical axis angle was measured in 40 patients with varus gonarthrosis from hip-to-ankle radiographs taken with patients in single-limb standing, double-limb standing, and supine positions. Kinematic and kinetic data were collected during walking and used to calculate the peak adduction moment about the knee. Repeated-measures analysis of variance and Scheffé post hoc tests indicated that mechanical axis angle measured on single-limb standing radiographs (-8.7 degrees +/- 4.0 degrees) was significantly greater than on double-limb standing radiographs (-7.1 degrees +/- 3.8 degrees), which was significantly greater than on supine radiographs (-5.5 degrees +/- 2.8 degrees). The peak knee adduction moment (2.8 +/- 0.8 percentage body weight x height) was only moderately correlated with mechanical axis angle on single-limb standing (r = -0.46), double-limb standing (r = -0.45), and supine (r = -0.43) radiographs. Patient position significantly affects frontal plane knee alignment. However, the peak knee adduction moment is only moderately correlated to mechanical axis angle, regardless of weightbearing status. These findings are inconsistent with the hypothesis that mechanical axis angle measured in single-limb standing is more representative of dynamic joint load and further highlight the differences between static and dynamic measures. Results also underscore the importance of reporting patient position during radiographs and keeping positions consistent when evaluating patients over time.


[Nursing consultation for chronic patients].
Nursing consultation for chronic patients forms part of the list of primary health care services for the coverage provided and due to the general public's satisfaction. However, the content and the results offered can be improved and the need to reorient this service has been proposed for quite some time. Strategies to succeed in developing a pure nursing contribution vis-a-vis our patients' health, that which we call an independent dimension in nursing, pass through the construction of a nursing vision which many of us lack as a consequence of a structured professional development along the lines of the biomedical model in which the nursing paradigm was transmitted more in the theoretical field than in the practical. By referring to Doka and Riopelle, we analyze the stages through which a patient afflicted by a physical disease passes and the tasks which he and his family should fulfill, in order to find an equivalence between these and some of the nursing diagnoses published by the North American Nursing Diagnosis Association (NANDA). The nursing diagnoses so obtained are compared to those which a panel of experts, belonging on Methodology Commission of the Malaga Sanitary District, by consensus identified as the most prevalent among this population. The degree of coincidences was high, which encourages us to continue along this vein in the nursing consultations for chronic patients.


Poverty, vulnerability, and provision of healthcare in Afghanistan.
This paper presents findings on conditions of healthcare delivery in Afghanistan. There is an ongoing debate about barriers to healthcare in low-income as well as fragile states. In 2002, the Government of Afghanistan established a Basic Package of Health Services (BPHS), contracting primary healthcare delivery to non-state providers. The priority was to give access to the most vulnerable groups: women, children, disabled persons, and the poorest households. In 2005, we conducted a nationwide survey, and using a logistic regression model, investigated provider choice. We also measured associations between perceived availability and usefulness of healthcare providers. Our results indicate that the implementation of the package has partially reached its goal: to target the most vulnerable. The pattern of use of healthcare provider suggests that disabled people, female-headed households, and poorest households visited health centres more often (during the year preceding the survey interview). But these vulnerable groups faced more difficulties while using health centres, hospitals as well as private providers and their out-of-pocket expenditure was higher than other groups. In the model of provider choice, time to travel reduces the likelihood for all Afghans of choosing health centres and hospitals. We situate these findings in the larger context of current debates regarding healthcare delivery for vulnerable populations in fragile state environments. The 'scaling-up process' is faced with several issues that jeopardize the objective of equitable access: cost of care, coverage of remote areas, and competition from profit-orientated providers. To overcome these structural barriers, we suggest reinforcing processes of transparency, accountability and participation.


Epidural analgesia: effects on labor progress and maternal and neonatal outcome.
The intended and unintended effects of epidural labor analgesia are reviewed. Mothers randomized to epidural rather than parenteral opioid analgesia have better pain relief. Fetal oxygenation is not affected by analgesic method; however, neonates whose mothers received intravenous or intramuscular opioids rather than epidural analgesia require more naloxone and have lower Apgar scores. Epidural analgesia does not affect the rates of cesarean delivery, obstetrically indicated instrumented vaginal delivery, neonatal sepsis, or new-onset back pain. Epidural analgesia is associated with longer second labor stages, more frequent oxytocin augmentation, and maternal fever (particularly among women who shiver and women receiving epidural analgesia for > 5 hours) but not with longer first labor stages. Epidural analgesia has no affect but intrapartum opioids decrease lactation success. Epidural use and urinary incontinence are weakly, but probably not causally, associated. Epidural labor analgesia would improve if the mechanisms of these unintended effects could be determined.


Monitoring of paces and gaits using binary PIR Sensors with rehabilitation treadmill.
Recently, rehabilitation treadmills are designed for helping injured persons such as stroke patients and injury athletes in the process of physical therapy. By monitoring the changes of paces and gaits, one can estimate the progress of rehabilitation. At present, most devices that can estimate paces and gaits are wearable and/or expensive. This paper presents an inexpensive, non-intrusive wireless binary sensor system for pace estimation and lower-extreme gait recognition with low data throughput and high energy efficiency. The asymmetric but periodic movement of injured person allows the study of pace and gait. The pace estimation is achieved by using autocorrelation function. The gait information is represented by three features (1) temporal correlation, (2) marginal density (intersection probability), and (3) spatial correlation from binary data steam. Experimental results shows that our system can estimate the pace of walking or running with the accuracy of 97.7%. By using only three features, abnormal gaits can also be recognized.


[Long-term results after operation of Achilles tendon rupture].
From 1973 to 1986 90 patients with rupture of Achilles' tendon were operated on (4 of these had open ruptures). Different surgical approaches were employed during the period under report. The assessment schemas after Arner/Lindholm and after Trillat formed the basis of both clinical follow-up and a questionnaire operation (participants were 81 patients 10 months to 14 years after the operation). 92.6% good and very good results confirmed the authors' concept of surgical treatment around the 4th or 5th day.


[Sinonasal NK/T-cell lymphoma mimicking Wegener's granulomatosis: a case report].
In Western population, sinonasal malignant lymphoma is rare and constitutes 1.5% of all non-Hodgkin lymphoma (NHL) and 2.2% of extranodal lymphomas. Wegener's granulomatosis (WG) is the necrotizing vasculitis of small arteries and veins. WG is characterized by granulomatous vasculitis and involves the upper and lower respiratory tract together with glomerulonephritis. But there are some forms of WG named limited WG that involves the upper respiratory tract only without glomerulonephritis and even seronegative without renal involvement. Herein, we present a typical WG with isolated sinonasal tract involvement with clinical, and radiological findings with the final diagnosis of NK/T-cell angiocentric lymphoma by the repeated biopsies. Since both diseases have same clinical and radiological findings differential diagnosis may be difficult.


Obesity does not alter vascular function and handgrip exercise hemodynamics in middle-aged patients with hypertension.
Lifestyle modification including exercise training is often the first line of defense in the treatment of obesity and hypertension (HTN), however, little is known regarding how these potentially compounding disease states impact vasodilatory and hemodynamic responses at baseline and exercise. Therefore, this study sought to compare the impact of obesity on vascular function and hemodynamics at baseline and during handgrip (HG) exercise among individuals with HTN. Non-obese (13M/7F, 56 ± 16 yr, 25 ± 4 kg/m2) and obese (17M/4F, 50 ± 7 yr, 35 ± 4 kg/m2) middle-aged individuals with HTN forwent antihypertensive medication use for ≥2 wk before assessment of vascular function by brachial artery flow-mediated dilation (FMD) and exercise hemodynamics during progressive HG exercise at 15-30-45% maximal voluntary contraction (MVC). FMD was not different between Non-Obese (4.1 ± 1.7%) and Obese (5.2 ± 1.9%, P = 0.11). Systolic blood pressure (SBP) was elevated by ∼15% during the supine baseline and during HG exercise in the obese group. The blood flow response to HG exercise at 30% and 45% MVC was ∼20% greater (P < 0.05) in the obese group but not different after normalizing for the higher, albeit, nonsignificant differences in workloads (MVC: obese: 24 ± 5 kg, non-obese: 21 ± 5 kg, P = 0.11). Vascular conductance and the brachial artery shear-induced vasodilatory response during HG were not different between groups (P > 0.05). Taken together, despite elevated SBP during HG exercise, obesity does not lead to additional impairments in vascular function and peripheral exercising hemodynamics in patients with HTN. Obesity may not be a contraindication when prescribing exercise for the treatment of HTN among middle-aged adults, however, the elevated SBP should be appropriately monitored.NEW & NOTEWORTHY This study examined vascular function and handgrip exercise hemodynamics in obese and nonobese individuals with hypertension. Obesity, when combined with hypertension, was neither associated with additional vascular function impairments at baseline nor peripheral hemodynamics and vasodilation during exercise compared with nonobese hypertension. Interestingly, systolic blood pressure and pulse pressure were greater in the obese group during supine baseline and exercise. These findings should not be ignored and may be particularly important for rehabilitation strategies.


Influence investigation of a void region on modeling light propagation in a heterogeneous medium.
A void region exists in some biological tissues, and previous studies have shown that inaccurate images would be obtained if it were not processed. A hybrid radiosity-diffusion method (HRDM) that couples the radiosity theory and the diffusion equation has been proposed to deal with the void problem and has been well demonstrated in two-dimensional and three-dimensional (3D) simple models. However, the extent of the impact of the void region on the accuracy of modeling light propagation has not been investigated. In this paper, we first implemented and verified the HRDM in 3D models, including both the regular geometries and a digital mouse model, and then investigated the influences of the void region on modeling light propagation in a heterogeneous medium. Our investigation results show that the influence of the region can be neglected when the size of the void is less than a certain range, and other cases must be taken into account.


The Frizzled family: receptors for multiple signal transduction pathways.
Frizzled genes encode integral membrane proteins that function in multiple signal transduction pathways. They have been identified in diverse animals, from sponges to humans. The family is defined by conserved structural features, including seven hydrophobic domains and a cysteine-rich ligand-binding domain. Frizzled proteins are receptors for secreted Wnt proteins, as well as other ligands, and also play a critical role in the regulation of cell polarity. Frizzled genes are essential for embryonic development, tissue and cell polarity, formation of neural synapses, and the regulation of proliferation, and many other processes in developing and adult organisms; mutations in human frizzled-4 have been linked to familial exudative vitreoretinopathy. It is not yet clear how Frizzleds couple to downstream effectors, and this is a focus of intense study.


Visible-Light-Induced Copper-Catalyzed Decarboxylative Coupling of Redox-Active Esters with N-Heteroarenes.
Herein we report a protocol for visible-light-induced copper-catalyzed decarboxylative coupling reactions between N-heteroarenes and redox-active esters. Various N-hydroxyphthalimide esters reacted with isoquinoline, quinoline, pyridine, pyrimidine, quinazoline, phthalazine, phenanthridine, and pyridazine to give the corresponding products in modest to excellent yields. The reactions proceed under mild conditions and have a broad scope and high functional group tolerance. Mechanistic studies revealed that the catalytic behavior of CuI photocatalyst generated in situ was consistent with that of preformed [Cu(dmp)(xantphos)]BF4.


Laser microdissection in clinical cardiovascular research.
Laser microdissection (LMD) is an accurate and fast method to procure pure populations of cells from complex, heterogeneous tissues under direct microscopic visualization. It can be applied to a wide range of cell preparation, including paraffin-embedded material. The morphology of the captured cells is retained, and DNA, RNA, and proteins can be extracted for molecular analysis. The potential applications of LMD to human cardiovascular research are multiple, including viral/autoimmune myocarditis and arteritis, atherosclerotic lesions, and myocardial and vascular cell proliferation and death. Molecular and genetic analysis of LMD-procured cells in cardiac and vascular tissues may provide a better understanding of several cardiac diseases.


[Long-term follow-up of interstitial laser coagulation in the treatment of benign prostatic hyperplasia].
Besides standard open or transurethreal adenoma resection, less morbid interstitial laser coagulation (ILC) is an alternative therapeutical option that could reduce lower urinary tract symptoms, especially in high-risk patients. Although short-term results indicate effectiveness, reliable long-term statistics are still lacking. Therefore, to assess long-term satisfaction and overall success rate, we re-evaluated patients with a mean follow-up of 7 years after laser treatment. A total of 72 patients had been included in our ILC programme between 1993 and 1995. Mean age was 74 years. About 45 % of the patients had since died of other causes. In all, 23 patients were evaluated by telephone questionnaire, International Prostate Symptom Score (IPSS), Quality of Life (QoL), second surgical interventions or medical therapy. Our patient group was treated with interstitial Nd:YAG laser coagulation (mediLas fibertom). A perineal (34 %), transurethral (23 %) or combined (43 %) approach was chosen, depending on the preoperative volume of the prostate (range 40 - 100 ml; mean 59.3 ml). 68.4 % of the patients were satisfied with their current urological situation. Mean IPSS was 8.8 vs. 18.8 preoperatively mean QoL 1.5 vs. 3.3. 15.8 % had undergone conventional transurethral prostatic resection in the interim; one patient uses a urine catheter. 15.8 % receive medical treatment for lower urinary tract symptoms. Although the results of standard TUR or open surgery imply higher success, the long-term results of ILC demonstrate effectiveness. Further follow-up studies on a larger number of patients are advisable. The low morbidity of ILC makes this procedure an interesting alternative option in the treatment of high risk patients.


An allosteric HTRA1-calpain 2 complex with restricted activation profile.
SignificanceClassic serine proteases are synthesized as inactive precursors that are proteolytically processed, resulting in irreversible activation. We report an alternative and reversible mechanism of activation that is executed by an inactive protease. This mechanism involves a protein complex between the serine protease HTRA1 and the cysteine protease calpain 2. Surprisingly, activation is restricted as it improves the proteolysis of soluble tau protein but not the dissociation and degradation of its amyloid fibrils, a task that free HTRA1 is efficiently performing. These data exemplify a challenge for protein quality control proteases in the clearing of pathogenic fibrils and suggest a potential for unexpected side effects of chemical modulators targeting PDZ or other domains located at a distance to the active site.


Efficacy of D-Wave Monitoring Combined With the Transcranial Motor-Evoked Potentials in High-Risk Spinal Surgery: A Retrospective Multicenter Study of the Monitoring Committee of the Japanese Society for Spine Surgery and Related Research.
Retrospective multicenter cohort study. We aimed to clarify the efficacy of multimodal intraoperative neuromonitoring (IONM), especially in transcranial electrical stimulation of motor-evoked potentials (TES-MEPs) with spinal cord-evoked potentials after transcranial stimulation of the brain (D-wave) in the detection of reversible spinal cord injury in high-risk spinal surgery. We reviewed 1310 patients who underwent TES-MEPs during spinal surgery at 14 spine centers. We compared the monitoring results of TES-MEPs with D-wave vs TES-MEPs without D-wave in high-risk spinal surgery. There were 40 cases that used TES-MEPs with D-wave and 1270 cases that used TES-MEPs without D-wave. Before patients were matched, there were significant differences between groups in terms of sex and spinal disease category. Although there was no significant difference in the rescue rate between TES-MEPs with D-wave (2.0%) and TES-MEPs (2.5%), the false-positivity rate was significantly lower (0%) in the TES-MEPs-with-D-wave group. Using a one-to-one propensity score-matched analysis, 40 pairs of patients from the two groups were selected. Baseline characteristics did not significantly differ between the matched groups. In the score-matched analysis, one case (2.5%) in both groups was a case of rescue (P = 1), five (12.5%) cases in the TES-MEPs group were false positives, and there were no false positives in the TES-MEPs-with-D-wave group (P = .02). TES-MEPs with D-wave in high-risk spine surgeries did not affect rescue case rates. However, it helped reduce the false-positivity rate.


Conversion due to vascular injury during video-assisted thoracic surgery lobectomy: A multicentre retrospective analysis from the Italian video-assisted thoracic surgery group registry.
Vascular injuries are among the most severe causes of unplanned conversion during VATS lobectomies. The study aimed to analyse the incidence of vascular injuries and their risk factors during VATS lobectomy. The Italian VATS lobectomy Registry was used to collect data from 66 Thoracic Surgery Units. From 2013 to October 2016 (out of more than 3,700 patients enrolled) only information from Units with an enrollment >100 VATS lobectomies were retrospectively analysed. Logistic regression analysis was performed on selected variables of the univariate analysis. Ten institutions contributed a total of 1,679 patients. Vascular injuries leading to conversion occurred in 44 (2.6%) patients. Years of experiences were inversely related to the risk of vascular injuries. Univariate analysis showed age, gender, surgical activity, Charlson Index Score and number of resected lymph nodes like significantly associated variables. Multivariate analysis revealed that number of resected lymph nodes, VATS experience ratio (number of VATS lobectomies/total lobectomies performed in the same year at same centre), and surgical activity of the centre were significantly associated with the risk of conversion. Unplanned thoracotomy was correlated with postoperative morbidity. Vascular injuries in VATS lobectomies represented a rare complication which could directly affect the postoperative outcomes. The predictive factors for conversion were multifactorial and depended on characteristics of centres and surgeons' seniority. Minimally invasive VATS lobectomy approaches did not influence the risk of vascular damages.


Observing responses and serial stimuli: searching for the reinforcing properties of the S-.
The control exerted by a stimulus associated with an extinction component (S-) on observing responses was determined as a function of its temporal relation with the onset of the reinforcement component. Lever pressing by rats was reinforced on a mixed random-interval extinction schedule. Each press on a second lever produced stimuli associated with the component of the schedule in effect. In Experiment 1 a response-dependent clock procedure that incorporated different stimuli associated with an extinction component of a variable duration was used. When a single S- was presented throughout the extinction component, the rate of observing remained relatively constant across this component. In the response-dependent clock procedure, observing responses increased from the beginning to the end of the extinction component. This result was replicated in Experiment 2, using a similar clock procedure but keeping the number of stimuli per extinction component constant. We conclude that the S- can function as a conditioned reinforcer, a neutral stimulus or as an aversive stimulus, depending on its temporal location within the extinction component.


Systemic amyloidoses.
The amyloidoses are a group of protein misfolding diseases in which the precursor protein undergoes a conformational change that triggers the formation of amyloid fibrils in different tissues and organs, causing cell death and organ failure. Amyloidoses can be either localized or systemic. In localized amyloidosis, amyloid deposits form at the site of precursor protein synthesis, whereas in systemic amyloidosis, amyloid deposition occurs distant from the site of precursor protein secretion. We review the type of proteins and cells involved and what is known about the complex pathophysiology of these diseases. We focus on light chain amyloidosis to illustrate how biochemical and biophysical studies have led to a deeper understanding of the pathogenesis of this devastating disease. We also review current cellular, tissue, and animal models and discuss the challenges and opportunities for future studies of the systemic amyloidoses.


Kupffer cell function in thyroid hormone-induced liver oxidative stress in the rat.
The influence of thyroid hormone (L-3, 3', 5-triiodothyronine, T3) on Kupffer cell function was studied in the isolated perfused rat liver by colloidal carbon infusion. Rates of carbon uptake were determined from the influent minus effluent concentration difference and the flow rate, and the respective carbon-induced respiratory activity was calculated by integration of the area under the O2 curves during carbon infusion. In the concentration range of 0.2 to 2.0 mg of carbon/ml, livers from euthyroid rats exhibited a sigmoidal-type kinetics of carbon uptake, with a Vmax of 4.8 mg/g liver/min and a concentration of 0.82 mg/ml for half-maximal rate; carbon-induced O2 uptake presented a hyperbolic-type kinetics, with a Vmax of 4.57 mumol of O2/g liver and a K(m) of 0.74 mg of carbon/ml, which significantly correlates with the carbon uptake rates. Light-microscopy showed that carbon was taken up exclusively by non-parenchymal cells, predominantly by Kupffer cells. Thyroid calorigenesis was found in parallel with increased rates of hepatic O2 consumption and thiobarbituric acid reactive substances (TBARS) formation, glutathione (GSH) depletion, and higher sinusoidal lactate dehydrogenase (LDH) efflux compared to control values. In the concentration range of 0.25 to 0.75 mg/ml, carbon infusion did not modify liver LDH efflux in control rats, while it was significantly enhanced in T3-treated animals. In this latter group, higher carbon concentrations (1 and 1.3 mg/ml) led to loss of viability of the liver. At 0.25 to 0.75 mg of carbon/ml, both the rates of carbon uptake and the associated carbon-induced respiratory activities were significantly increased by T3 treatment, effects that were abolished by pretreatment of the rats with gadolinium chloride (GdCl3). In addition, GdCl3 decreased by 50% the changes induced by T3 in hepatic GSH content and TBARS formation. It is concluded that hyperthyroidism enhances Kupffer cell function, correlated with the increased number of liver macrophages observed histologically, which may represent an alternate source of reactive O2 species to that induced in parenchymal cells, thus contributing to the enhanced oxidative stress status developed.


Benzoquinone, a leukemogenic metabolite of benzene, catalytically inhibits the protein tyrosine phosphatase PTPN2 and alters STAT1 signaling.
Protein tyrosine phosphatase, nonreceptor type 2 (PTPN2) is mainly expressed in hematopoietic cells, where it negatively regulates growth factor and cytokine signaling. PTPN2 is an important regulator of hematopoiesis and immune/inflammatory responses, as evidenced by loss-of-function mutations of PTPN2 in leukemia and lymphoma and knockout mice studies. Benzene is an environmental chemical that causes hematological malignancies, and its hematotoxicity arises from its bioactivation in the bone marrow to electrophilic metabolites, notably 1,4-benzoquinone, a major hematotoxic benzene metabolite. Although the molecular bases for benzene-induced leukemia are not well-understood, it has been suggested that benzene metabolites alter topoisomerases II function and thereby significantly contribute to leukemogenesis. However, several studies indicate that benzene and its hematotoxic metabolites may also promote the leukemogenic process by reacting with other targets and pathways. Interestingly, alterations of cell-signaling pathways, such as Janus kinase (JAK)/signal transducer and activator of transcription (STAT), have been proposed to contribute to benzene-induced malignant blood diseases. We show here that 1,4-benzoquinone directly impairs PTPN2 activity. Mechanistic and kinetic experiments with purified human PTPN2 indicated that this impairment results from the irreversible formation (kinact = 645 m-1·s-1) of a covalent 1,4-benzoquinone adduct at the catalytic cysteine residue of the enzyme. Accordingly, cell experiments revealed that 1,4-benzoquinone exposure irreversibly inhibits cellular PTPN2 and concomitantly increases tyrosine phosphorylation of STAT1 and expression of STAT1-regulated genes. Our results provide molecular and cellular evidence that 1,4-benzoquinone covalently modifies key signaling enzymes, implicating it in benzene-induced malignant blood diseases.


Effect of Na2O and ZnO on the microstructure and properties of laser cladding derived CaO-SiO2 ceramic coatings on titanium alloys.
To improve the bioactivity of titanium alloy (Ti-6Al-4V), CaO-SiO2 coatings on titanium alloys were fabricated using laser cladding method. The effect of Na2O and ZnO on the microstructure and properties of the prepared coatings was discussed. The microstructure of the CaO-SiO2 coatings consists of cellular grains and cellular dendrites. The mutual diffusion of elements occurs between the coating and substrate. The base CaO-SiO2 coating is composed of different phases including CaTiO3, α-Ca2(SiO4), SiO2, TiO2 and CaO. The formation of CaTiO3 in the ceramic layer was analyzed through thermodynamics. Na2O has little influence on the microstructure, average hardness and wear resistance. When ZnO is added to the precursor, the microstructure turns to cell dendrite, and ZnO and Zn2SiO4 appear in the corresponding coating. The addition of ZnO reduces the average hardness and wear resistance of the ceramic layer. The in vitro soaking in SBF shows that the laser cladding coating has the ability to form an apatite layer.


Relationships Between a Range of Inflammatory Biomarkers and Subjective Sleep Quality in Chronic Insomnia Patients: A Clinical Study.
To examine whether associations exist between chronic insomnia disorder (CID) and overlooked inflammatory factors (Serum amyloid protein A [SAA]), tumor necrosis factor [TNF]-α, granulocyte-macrophage colony-stimulating factor [GM-CSF], and regulated on activation and normal T cell expressed and presumably secreted [RANTES]). A total of 65 CID patients and 39 sex- and age-matched good sleeper (GS) controls participated in this study. They completed a baseline survey to collect data on demographics, and were elevated sleep and mood by Pittsburgh Sleep Quality Index (PSQI), Athens Insomnia Scale (AIS), 17-item Hamilton Depression Rating Scale (HAMD-17) and 14-item Hamilton Anxiety Rating Scale (HAMA-14), respectively. The blood samples were collected and tested the serum levels of SAA, TNF-α, GM-CSF and RANTES. The CID group had higher serum levels of SAA, TNF-α, and GM-CSF and a lower level of RANTES than the GS group. In the Spearman correlation analysis, SAA and GM-CSF positively correlated with the PSQI and AIS scores. After controlling for sex, HAMD-17 score, and HAMA-14 score, the partial correlation analysis showed that GM-CSF was positively correlated with PSQI score. Further stepwise linear regression analyses showed that GM-CSF was positively associated with the PSQI and AIS scores, while RANTES was negatively associated with them, and SAA was positively associated with just the AIS score. The serum levels of inflammatory mediators (SAA, TNF-α, and GM-CSF) were significantly elevated and the level of RANTES was significantly decreased in CID patients and, to some extent, the changes are related to the severity of insomnia. These findings may help us to improve interventions to prevent the biological consequences of CID by inhibiting inflammation, thereby promoting health.


The influence of supraspinal impulse activity on the intra-axonal transport of transmitter-related substances in rat motor neurons.
The content and intra-axonal transport of acetylcholine (ACh) and the ACh-metabolizing enzymes choline-acetyl-transferase (CAT) and ACh-esterase (AChE) in the rat sciatic nerve were studied after various experimental procedures. The procedures involved: (1) spinal cord transection (SCT) at the thoracic level 1 day to 3 weeks prior to experiments, to abolish nerve activity of the lower motor neurons (in the lumbar intumescence-sciatic nerve) from supraspinal centres; (2) physical training for 2 h daily during 2 weeks in a rodent treadmill, to increase nerve activity from supraspinal levels; and (3) the use of selective neurotoxins to cause degeneration of descending bulbospinal monoaminergic (MA) neurons. The results of these studies demonstrate that supraspinal nerve influence can modify the axonal transport of ACh and cholinergic enzymes in the rat sciatic nerve, and that descending monoamine (MA) pathways may, at least to some extent, participate in this modulation of intraneuronal dynamics in the motor neuron. Since it has been shown by many investigators that factors which have a trophic influence on skeletal muscle cells both in vitro and in vivo are present in motor nerves and transported along the axons in a distal direction, we suggest that the synthesis and axonal transport of such factors may also be under control of supraspinal nerve activity. Therefore, it is possible that metabolic changes and dystrophy of muscles occurring in patients with lesions of the 'upper motor neuron-type' may also, in addition to other factors, be dependent on changes in intra-axonal transport of various substances in the lower motor neuron.


Localization of the 7H6 antigen at tight junctions correlates with the paracellular barrier function of MDCK cells.
An important function of the tight junction is to act as a selective barrier to ions and small molecules, although no molecule responsible for the barrier function has been identified. Here we report evidence that the localization of the 7H6 tight junction-associated antigen identified in our laboratory at tight junctions correlates with the barrier function of MDCK cells. MDCK cells in a confluent monolayer possessed a polarized morphology, having an apical plasma membrane and a basolateral membrane, which is separated from the former by tight junctions. MDCK cells expressed both ZO-1 and 7H6 antigen at tight junctions, which maintain a tight barrier as determined by resistance to lanthanum permeation and high transepithelial electrical resistance (TER, 1500 ohm-cm2). The 7H6 antigen disappeared as tight junctions became permeable to lanthanum with a decrease in TER (below 100 ohm-cm2) due to treatment with metabolic inhibitors (10 microns antimycin A and 10 mM 2-deoxyglucose) for 30 min, while leaving ZO-1 at the cell border. The 7H6 antigen appeared at tight junctions again as TER recovered to a high level (1500 ohm-cm2) within 3 h after withdrawal of metabolic inhibitors. In addition, we found that 7H6 antigen is a phosphorylated protein and that phosphorylation is closely related to the localization of 7H6 antigen in the area of tight junctions.


Local and long-range GABAergic circuits in hippocampal area CA1 and their link to Alzheimer's disease.
GABAergic inhibitory neurons are the principal source of inhibition in the brain. Traditionally, their role in maintaining the balance of excitation-inhibition has been emphasized. Beyond homeostatic functions, recent circuit mapping and functional manipulation studies have revealed a wide range of specific roles that GABAergic circuits play in dynamically tilting excitation-inhibition coupling across spatio-temporal scales. These span from gating of compartment- and input-specific signaling, gain modulation, shaping input-output functions and synaptic plasticity, to generating signal-to-noise contrast, defining temporal windows for integration and rate codes, as well as organizing neural assemblies, and coordinating inter-regional synchrony. GABAergic circuits are thus instrumental in controlling single-neuron computations and behaviorally-linked network activity. The activity dependent modulation of sensory and mnemonic information processing by GABAergic circuits is pivotal for the formation and maintenance of episodic memories in the hippocampus. Here, we present an overview of the local and long-range GABAergic circuits that modulate the dynamics of excitation-inhibition and disinhibition in the main output area of the hippocampus CA1, which is crucial for episodic memory. Specifically, we link recent findings pertaining to GABAergic neuron molecular markers, electrophysiological properties, and synaptic wiring with their function at the circuit level. Lastly, given that area CA1 is particularly impaired during early stages of Alzheimer's disease, we emphasize how these GABAergic circuits may contribute to and be involved in the pathophysiology.


[Tinnitus and stenosis of the cavernous internal carotid artery].
We report a case of isolated unilateral pulsatile tinnitus. Cerebral angiography showed a right intra-cranial internal carotid artery stenosis. Treatment by dilatation and stenting resulted in symptom resolution.


The Gambee intestinal anastomosis in gynecologic surgery.
The Gambee single-layer, through-and-through, catgut suture anastomosis of the gastrointestinal tract has been in use from 1969 to 1974. Sixty-four anastomoses have been performed on 56 patients with gastrointestinal involvement or pelvic malignancy. There were no operative deaths, and no patients required reoperation for correction of intestinal anastomotic leaks or rupture of the suture line. This experience suggests that the Gambee intestinal single-layer anastomosis may be useful in the management of gastrointestinal complications of pelvic surgery and malignancy.


Ultrasonographic measurement of the adrenal gland-to-abdominal aortic ratio as a valuable method of estimating normal adrenal size in rabbits.
A wide range has been reported for the ultrasonographic measurements of the normal adrenal gland in rabbits. Therefore, having sufficient information about the normal measurements of the adrenal gland and their relationship with indicators such as weight, sex and the diameter of the internal abdominal aorta will be of great help in diagnosing diseases of the adrenal gland. In the present study, 21 healthy adult intact rabbits were selected. The abdominal cavity of the animals was examined using ultrasound; adrenal gland parameters such as length, width, height, circumference and area on the right and left sides were measured in both sagittal and transverse planes. Additionally, the diameter of the abdominal aorta in the sagittal plane was imaged. After statistical analysis, the parameters of the adrenal glands on the right and left showed a positive significant correlation with the weight and the diameter of the abdominal aorta, although no significant correlation was found between these parameters and sex. The ratio of adrenal gland parameters to abdominal aortic diameter was calculated and the statistical analysis of the values showed that, except for the ratio of left adrenal area to aortic diameter, the other ratio of adrenal gland parameters to abdominal aortic diameter was not significantly related to weight. Therefore, these ratios can be used as suitable indicators for assessing the change in size of the adrenal gland of rabbits of different sizes. Knowing the relationship between normal adrenal measurements and the indices such as weight, sex and diameter of the abdominal aorta can help clinicians and researchers evaluate the changes in the size of the adrenal gland.


Investigating Links Between Fear of COVID-19, Neuroticism, Social Networks Use Disorder, and Smartphone Use Disorder Tendencies.
The present study investigates links between fear of COVID-19, the personality trait of neuroticism, social networks use disorder, and smartphone use disorder (SNUD and SmUD, respectively) tendencies. In an online survey, N = 932 participants recruited at a Chinese University (237 males and 695 females) completed self-reports on fear of COVID-19, neuroticism (and other personality traits from the Big Five Inventory-44), the Bergen Social Media Addiction Scale (assessing tendencies toward SNUD), and the Smartphone Addiction Scale short version-assessing individual differences in tendencies toward SmUD. Our findings showed that all variables of main interest were positively correlated with each other. A mediation model suggested that SNUD (in parts) mediated the association between fear of COVID-19 and SmUD. Although neuroticism was robustly correlated with all mentioned variables, no moderation effect could be observed on the investigated fear-of-COVID-19-SNUD-link. The findings of this work provide further evidence that the smartphone itself is only a device giving individuals access to software applications, which might be excessively used. Beyond that, the present data indicate neuroticism to be a risk factor with respect to fear of COVID-19, SNUD, and SmUD, although the study is limited by its cross-sectional study design.


Formation of quaternary stereogenic centers by NHC-Cu-catalyzed asymmetric conjugate addition reactions with Grignard reagents on polyconjugated cyclic enones.
The copper-catalyzed conjugate addition of various Grignard reagents to polyconjugated enones (dienone and enynone derivatives) is reported. The catalyst system, composed of copper triflate and an NHC ligand, led to the unusual selective formation of the 1,4-addition products. This reaction allows for the creation of all-carbon chiral quaternary centers with enantiomeric excesses up to 99%. The remaining unsaturation on the 1,4 adducts give access to valuable synthetic transformations.


New High-Power LEDs Open Photochemistry for Near-Infrared-Sensitized Radical and Cationic Photopolymerization.
Cyanines derived from heptamethines were investigated in combination with iodonium salts as initiators of the radical polymerization of tripropylene glycol diacrylate and epoxides derived from bisphenol-A-diglycidylether. A new near-infrared (NIR) LED prototype emitting at 805 nm with an exposure intensity of 1.2 W cm-2 facilitated initiation of both radical and cationic polymerization using sensitizers derived from cyanines. This new light-emitting device has brought new insight into the photochemistry of cyanines with the general structure 1 because a combination of photonic and thermal processes strongly influences reaction pathways. In particular, cationic cyanines comprising a cyclopentene moiety and diphenylamino group in the center initiated the cationic polymerization of epoxides. Selective oxidation of this unit explains why specifically these derivatives may function as initiators for cationic polymerization. In contrast, when the diphenylamino group was replaced by a barbital group at the meso-position cationic polymerization of epoxides was not initiated.


Prognostic value of human papillomavirus 16/18 genotyping in low-grade cervical lesions preceded by mildly abnormal cytology.
Histological low-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 1 (LSIL/CIN1) preceded by normal or mildly abnormal cytology is recommended for conservative follow-up, with no separated management. In this study, we assessed the triage value of human papillomavirus (HPV) 16/18 genotyping in 273 patients with LSIL/CIN1. HPV16/18 genotyping was performed at baseline and follow-up was at 6-monthly intervals for up to 2 years. At each follow-up, women positive for cytology or high-risk HPV (hrHPV) were referred for colposcopy. Enrollment cytology, HPV16/18 genotyping, and questionnaire-obtained factors were linked to the 2-year cumulative progression rate. Univariate and multivariate analyses were performed taking into account time-to-event with Cox proportional hazard regression. The results showed that 190 cases (69.6%) regressed, 37 (13.6%) persisted, and 46 (16.8%) progressed. HPV16/18 positivity (hazard ratio (HR), 2.708; 95% confidence interval (CI), 1.432-5.121; P=0.002) is significantly associated with higher 2-year cumulative progression rate. Sub-analysis by enrollment cytology and age restricted the positive association among patients preceded by mildly abnormal cytology and aged 30 years or older. Immediate treatment is a rational recommendation for the high-risk subgroup, when good compliance is not assured.


Foveal Hypoplasia in Patients with Stickler Syndrome.
To determine the microstructure of the fovea in patients with Stickler syndrome using imaging by spectral-domain optical coherence tomography (SD OCT) and swept-source OCT. Retrospective case series study. A total of 39 eyes of 25 patients with genetically confirmed Stickler syndrome were studied. All of the patients had mutations in the COL2A1 gene and were diagnosed with Stickler syndrome. Cross-sectional OCT images, OCT angiography (OCTA), and en face OCT images were assessed. The ratio of the foveal inner retinal layer (fIRL) thickness to the parafoveal inner retinal layer (pIRL) thickness, the ratio of the foveal outer retinal layer (fORL) thickness to the parafoveal outer retinal layer (pORL) thickness, and the size of the foveal avascular zone (FAZ) were determined. The degree of foveal hypoplasia and the best-corrected visual acuity in patients with Stickler syndrome. A persistence of the inner retinal layers in the fovea with an fIRL/pIRL ratio >0.2 was present in 32 of the 39 eyes (82%). Optical coherence tomography angiography showed that the FAZ was smaller, 0 to 0.19 mm2, than that of normal eyes, in 25 eyes of 17 patients who underwent OCTA. There was no significant correlation between the visual acuities and the fIRL/pIRL ratios. A mild foveal hypoplasia with a persistence of the IRL is characteristic of eyes with Stickler syndrome. The visual acuities were not correlated with the fIRL/pIRL ratios.


Transient Type 3 Renal Tubular Acidosis during Cyclic Vomiting Syndrome.
Type 3 renal tubular acidosis is a pathological condition characterized by the simultaneous occurrence of distal renal tubular acidosis, which causes urinary acidification disorders, and proximal renal tubular acidosis, which causes impaired reabsorption of bicarbonate ions. Type 3 renal tubular acidosis is considered rare. A 5-year-old boy was admitted to our hospital because of frequent vomiting, poor vitality, and fever. He was diagnosed with cyclic vomiting syndrome. Type 3 renal tubular acidosis was also diagnosed because of severe mixed metabolic acidosis with impaired urinary acidification, a low tubular phosphorus reabsorption rate with hypophosphatemia, low-molecular-weight proteinuria, pan-aminoaciduria, and glucosuria. Fluid infusion was performed. On the second day of hospitalization, the vomiting disappeared and the patient was able to eat and drink. He was discharged on the eighth day of hospitalization. The laboratory test abnormalities associated with the renal tubular acidosis gradually improved, and testing at discharge on the eighth day of admission showed no metabolic acidosis, hypophosphatemia, low-molecular-weight proteinuria, or glucosuria. These findings suggested that the type 3 renal tubular acidosis was transient. Severe metabolic acidosis was observed in this patient because of both normal anion gap metabolic acidosis due to type 3 renal tubular acidosis and anion gap metabolic acidosis due to cyclic vomiting syndrome. Although type 3 tubular acidosis is rare, the resultant metabolic acidosis worsens when combined with a disease that causes metabolic acidosis. Type 3 tubular acidosis should be ruled out when severe metabolic acidosis is present.


A systematic review of the factors affecting choice of surgery as a career.
Interest in surgical careers among medical students has declined over the past decade. Multiple explanations have been offered for why top students are deterred or rejected from surgical programs, though no consensus has emerged. We conducted a review of the literature to better characterize what factors affect the pursuit of a surgical career. We searched PubMed and EMBASE and performed additional reference checks. Agency for Healthcare Research and Quality (AHRQ) and Newcastle-Ottawa Education scores were used to evaluate the included data. Our search identified 122 full-text, primary articles. Analysis of this evidence identified 3 core concepts that impact surgical career decision-making: gender, features of surgical education, and student "fit" in the culture of surgery. Real and perceived gender discrimination has deterred female medical students from entering surgical careers. In addition, limited exposure to surgery during medical school and differences between student and surgeon personality traits and values may deter students from entering surgical careers. We suggest that deliberate and visible effort to include women and early-career medical students in surgical settings may enhance their interest in carreers in surgery.


Genetic structure of nest aggregations and drone congregations of the southeast Asian stingless bee Trigona collina.
In stingless bees, sex is determined by a single complementary sex-determining locus. This method of sex determination imposes a severe cost of inbreeding because an egg fertilized by sperm carrying the same sex allele as the egg results in a sterile diploid male. To explore how reproductive strategies may be used to avoid inbreeding in stingless bees, we studied the genetic structure of a population of 27 colonies and three drone congregations of Trigona collina in Chanthaburi, Thailand. The colonies were distributed across six nest aggregations, each aggregation located in the base of a different fig tree. Genetic analysis at eight microsatellite loci showed that colonies within aggregations were not related. Samples taken from three drone congregations showed that the males were drawn from a large number of colonies (estimated to be 132 different colonies in our largest swarm). No drone had a genotype indicating that it could have originated from the colony that it was directly outside. Combined, these results suggest that movements of drones and possibly movements of reproductive swarms among colony aggregations provide two mechanisms of inbreeding avoidance.


Indication for hyperbaric oxygen treatment as a predictor of tympanostomy tube placement.
Hyperbaric oxygen therapy (HBO2) has been utilized for many years for a multitude of disease entities. One commonly encountered side-effect is otic barotrauma. To determine if patients with specific disease processes are at increased risk of requiring tympanostomy tubes during HBO2. Data was obtained from Jan. 2000 to Dec. 2004, retrospectively. The requirement for tympanostomy tubes during a course of HBO2 was established. 325 met inclusion criteria. Fifteen percent of patients overall (95% CI= 11-19%) required tympanostomy tubes. Tubes were required in: 5% necrotizing soft tissue infection (p=0.33); 10% failed/threatened graft (p=0.39); 15% problem wounds; 17% chronic refractory osteomyelitis (CRO) (p=0.64); 22% soft tissue radionecrosis (STRN)/osteoradionecrosis (ORN) (p=0.02); 33% of crush injuries (p=0.10). Twenty-nine percent of nasopharyngeal radiation injury patients (p=0.001) and 10% of the non-nasopharyngeal radiation patients (p=0.36) received tympanostomy tubes. A significant increase in tympanostomy tubes were required in nasopharyngeal radiation injury patients.


Association between polycystic ovary syndrome and the risk of stroke and all-cause mortality: insights from a meta-analysis.
Many epidemiologic literatures have investigated the link between PCOS and long-term stroke risk and all-cause mortality, but the results are surprisingly conflicting. A meta-analysis was performed to examine the link between polycystic ovary syndrome (PCOS) and the risk of stroke, death from any cause, and assessed whether BMI might explain a higher risk of stroke. We searched the PUBMED, EMBASE, and Cochrane Library databases with no restrictions. Nine Cohort studies were identified, involving a total of 237,647 subjects. Compared with those without PCOS, subjects with PCOS were significantly associated with a increased risk of developing stroke (OR = 1.36; 95% CI 1.09-1.70; p = .007). However, no significant association was observed between PCOS and all-cause death (OR = 1.21; 95% CI 0.88-1.66; p = .25). Moreover, after pooling the five studies with risk estimates adjusted for BMI, the association between PCOS and stroke was slightly attenuated, although the odds ratios did not reach statistical significance (OR = 1.24; 95% CI 0.98-1.59). In conclusion, PCOS is associated with significant increased risk for stroke, while there is no consistent evidence to indicate that PCOS influences all-cause death outcomes. Increased BMI is an important contributor to the relationship between PCOS and stroke risk. Further study is needed to clarify which subgroups of subjects with the PCOS are at higher risk for stroke and should focus on developing reliable device for risk stratification.


Refined control of CRISPR-Cas9 gene editing in Clostridium sporogenes: the creation of recombinant strains for therapeutic applications.
Despite considerable clinical success, the potential of cancer immunotherapy is restricted by a lack of tumour-targeting strategies. Treatment requires systemic delivery of cytokines or antibodies at high levels to achieve clinically effective doses at malignant sites. This is exacerbated by poor penetration of tumour tissue by therapeutic antibodies. High-grade immune-related adverse events (irAEs) occur in a significant number of patients (5-15%, cancer- and therapeutic-dependent) that can lead to lifelong issues and can exclude from treatment patients with pre-existing autoimmune diseases. Tumour-homing bacteria, genetically engineered to produce therapeutics, is one of the approaches that seeks to mitigate these drawbacks. The ability of Clostridium sporogenes to form spores that are unable to germinate in the presence of oxygen (typical of healthy tissue) offers a unique advantage over other vectors. However, the limited utility of existing gene editing tools hinders the development of therapeutic strains. To overcome the limitations of previous systems, expression of the Cas9 protein and the gRNA was controlled using tetracycline inducible promoters. Furthermore, the components of the system were divided across two plasmids, improving the efficiency of cloning and conjugation. Genome integrated therapeutic genes were assayed biochemically and in cell-based functional assays. The potency of these strains was further improved through rationally-conceived gene knock-outs. The new system was validated by demonstrating the efficient addition and deletion of large sequences from the genome. This included the creation of recombinant strains expressing two pro-inflammatory cytokines, interleukin-2 (IL-2) and granulocyte macrophage-colony stimulating factor (GM-CSF), and a pro-drug converting enzyme (PCE). A comparative, temporal in vitro analysis of the integrant strains and their plasmid-based equivalents revealed a substantial reduction of cytokine activity in chromosome-based constructs. To compensate for this loss, a 7.6 kb operon of proteolytic genes was deleted from the genome. The resultant knock-out strains showed an 8- to 10-fold increase in cytokine activity compared to parental strains.


Dental and Periodontal Treatment Need after Dental Clearance Is Not Associated with the Outcome of Induction Therapy in Patients with Acute Leukemia: Results of a Retrospective Pilot Study.
This retrospective pilot study aimed to detect whether remaining dental/periodontal treatment need and periodontal inflammation after dental clearance would be associated with the initial therapy outcome of adult patients with acute leukemia undergoing induction chemotherapy. Different parameters were assessed from the patients' records: initial blood parameters, blood parameters during initial chemotherapy, leukemia/therapy related complaints, duration of fever, microbiological findings (blood and urine), as well as patients' survival. Dental treatment need was defined as the presence of at least one carious tooth; periodontal treatment need was determined by the presence of probing depth ≥3.5 mm in at least two sextants. To reflect periodontal inflammation, the periodontal inflamed surface area (PISA) was applied. Thirty-nine patients were included. A dental treatment need of 75% and periodontal treatment need of 76% as well as an average PISA of 153.18 ± 158.09 were found. Only two associations were detected: periodontal treatment need was associated with thrombocyte count after 7 days (p=0.03), and PISA was associated with erythrocyte count three days after induction of therapy (p=0.01). It can be concluded that remaining dental and periodontal treatment need as well as periodontal inflammation after dental clearance is not associated with the outcome of induction therapy in adult patients with acute leukemia.


Efficacy and safety of pulsed radiofrequency as a method of dorsal root ganglia stimulation for treatment of non-neuropathic pain: a systematic review.
We systematically reviewed the evidence on the efficacy and safety of dorsal root ganglion (DRG) targeted pulsed radiofrequency (PRF) versus any comparator for treatment of non-neuropathic pain. We searched MEDLINE, CINAHL, Embase, PsycINFO, clinicaltrials.gov and WHO clinical trial register until January 8, 2019. All study designs were eligible. Two authors independently conducted literature screening. Primary outcomes were pain intensity and serious adverse events (SAEs). Secondary outcomes were any other pain-related outcome and any other safety outcome that was reported. We assessed the risk of bias using the Cochrane tool and Risk of Bias In Non-randomized Studies of Interventions (ROBINS-I). We conducted narrative evidence synthesis and assessed the conclusiveness of included studies regarding efficacy and safety. We included 17 studies with 599 participants, which analyzed various pain syndromes. Two studies were randomized controlled trials; both included participants with low back pain (LBP). Non-randomized studies included patients with the following indications: LBP, postsurgical pain, pain associated with herpes zoster, cervicogenic headache, complex regional pain syndrome type 1, intractable vertebral metastatic pain, chronic scrotal and inguinal pain, occipital radiating pain in rheumatoid arthritis and chronic migraine. In these studies, the PRF was usually initiated after other treatments have failed. Eleven studies had positive conclusive statements (11/17) about efficacy; the remaining had positive inconclusive statements. Only three studies provided conclusiveness of evidence statements regarding safety - two indicated that the evidence was positive conclusive, and one positive inconclusive. The risk of bias was predominantly unclear in randomized and serious in non-randomized studies. Poor quality and few participants characterize evidence about benefits and harms of DRG PRF in patients with non-neuropathic pain. Results from available studies should only be considered preliminary. Not all studies have reported data regarding the safety of the intervention, but those that did, indicate that the intervention is relatively safe. As the procedure is non-destructive and early results are promising, further comparative studies about PRF in non-neuropathic pain syndromes would be welcomed.


Adult burn survivors' views of peer support: a qualitative study.
This qualitative study examined 30 burn survivors' perceptions of the value of peer support in their own psychosocial rehabilitation. Little research is available that investigates the role of peer support in post-burn recovery in terms of perceived benefits and costs. Findings revealed strong positive views regarding the helpfulness of peer support. Burn survivors reported that peer supporters provided a sense of belonging and affiliation and gave hope and confidence. Two-thirds of the sample had served as peer supporters themselves after receiving their injuries, suggesting that mutual aid does involve reaching out to others. At the same time, survivors spoke of possible costs in helping others. Involving peer supporters in the psychological rehabilitation of burn survivors may be an important complement to the medical team.


Arguing by analogy in the fetal tissue debate.
In the debate over fetal tissue use, an analogy is often drawn between removing organs from the body of a person who has been murdered to use for transplantation, and collecting tissue from an aborted fetus to use for the same purpose. The murder victim analogy is taken by its proponents to show that even if abortion is the moral equivalent of murder, there is still no good reason to refrain from using the fetal tissue, since as a society we do not see any problem about using organs from murder victims. However, I argue that the analogy between murder victims and aborted fetuses does not hold -- the two situations are not the same in all morally relevant respects. Thus the murder victim analogy does not provide an argument in favour of fetal tissue transplant. In conclusion, I point to some of the potential pitfalls of using analogies in ethical argument.


Kinship Identities in the Context of UK Maternal Spindle Transfer and Pronuclear Transfer Legislation.
In the discussions leading up to the enactment of the UK Human Fertilisation and Embryology (Mitochondrial Donation) Regulations 2015, it was repeatedly emphasised, by many commentators, that maternal spindle transfer (MST) and pronuclear transfer (PNT) did not give rise to children who could be considered as having three or more parents. This was because it was argued that only the genetic material found in the chromosomes should be considered as the determining factor for the formation of parent-child relationships and the resulting kinship identities. In this present study, however, this assertion will be questioned in the light of different kinds and different understandings of kinship identities. It will also be suggested that any person who is partly responsible for the very existence of a child, through any means, may qualify as a causal parent - a parent whom the resulting child may want to identify. As a result, a positive response should be given to a request from a person born from MST and PNT concerning identifying information for all the individuals responsible for bringing him or her into existence. In the light of this, the article will conclude that it is regrettable that the UK government enacted binding legislation making sure that children, born through MST and PNT, will never be able to contact the egg donors and, in the case of PNT, the sperm donors. This reflects a very limited understanding of who parents really are and may give rise to serious long-term psychological distress in the prospective children.


Impact of common regulatory single-nucleotide variants on gene expression profiles in whole blood.
Genome-wide association studies (GWASs) have uncovered susceptibility loci for a large number of complex traits. Functional interpretation of candidate genes identified by GWAS and confident assignment of the causal variant still remains a major challenge. Expression quantitative trait (eQTL) mapping has facilitated identification of risk loci for quantitative traits and might allow prioritization of GWAS candidate genes. One major challenge of eQTL studies is the need for larger sample numbers and replication. The aim of this study was to evaluate the robustness and reproducibility of whole-blood eQTLs in humans and test their value in the identification of putative functional variants involved in the etiology of complex traits. In the current study, we performed comphrehensive eQTL mapping from whole blood. The discovery sample included 322 Caucasians from a general population sample (KORA F3). We identified 363 cis and 8 trans eQTLs after stringent Bonferroni correction for multiple testing. Of these, 98.6% and 50% of cis and trans eQTLs, respectively, could be replicated in two independent populations (KORA F4 (n=740) and SHIP-TREND (n=653)). Furthermore, we identified evidence of regulatory variation for SNPs previously reported to be associated with disease loci (n=59) or quantitative trait loci (n=20), indicating a possible functional mechanism for these eSNPs. Our data demonstrate that eQTLs in whole blood are highly robust and reproducible across studies and highlight the relevance of whole-blood eQTL mapping in prioritization of GWAS candidate genes in humans.


Influence of Oligonucleotide Grafting Density on Surface-Mediated DNA Transport and Hybridization.
Adsorption of soluble DNA to surfaces decorated with complementary DNA plays an important role in many bionanotechnology applications, and previous studies have reported complex dependencies of the surface density of immobilized DNA on hybridization. While these effects have been speculatively ascribed to steric or electrostatic effects, the influence of surface-mediated molecular transport (i.e., intermittent "hopping diffusion") has not been fully appreciated. Here, single-molecule tracking and Förster resonance energy transfer (FRET) were employed to characterize the mobility and the hybridization efficiency of adsorbed ssDNA oligonucleotides ("target") at solid-liquid interfaces exhibiting surface-immobilized ssDNA ("probe") over a wide range of surface grafting densities. Two distinct regimes were observed, with qualitatively different transport and hybridization behaviors. At dilute grafting density, only 1-3% of target molecules were observed to associate with probes (i.e., to hybridize). Adsorbing target molecules often searched unsuccessfully and "flew", via desorption-mediated diffusion, to secondary locations before hybridizing. In contrast, at high probe grafting density, approximately 20% of target DNA hybridized to immobilized probes, and almost always in the vicinity of initial adsorption. Moreover, following a dehybridization event, target molecules rehybridized at high probe density, but rehybridization was infrequent in the dilute density regime. Interestingly, the intermittent interfacial transport of mobile target molecules was suppressed by the presence of immobilized probe DNA, presumably due to an increased probability of readsorption following each "hop". Together, these findings suggested that many salient effects of grafting density on surface-mediated DNA hybridization can be directly related to the mechanisms of surface-mediated intermittent diffusion.


Is EMA warning on quinolones and fluoroquinolones really assessed? An EudraVigilance database analysis.
On March 11th 2019, European Medicines Agency (EMA) issues a warning after a review of serious, disabling and potentially permanent adverse events (AEs), particularly on musculoskeletal and nervous system, with quinolone (QN) and fluoroquinolone (FQ) antibiotics. Aim of this study was to evaluate the effect of the EMA warning on the rate of AEs after QN and FQ treatments, reported in the EudraVigilance (EV) database. EV database is the system for managing and analyzing information on suspected AEs to medicines which have been authorized or being studied in clinical trials in the European Economic Area (EEA). We retrospectively explored the effect of FQs and QNs on musculoskeletal and nervous system from the EMA warning up to now (21 months) and compared these results with the 21 months before the EMA warning. Main part of AEs in EV database were reported for ciprofloxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin. Ciprofloxacin total AEs before 21 months till 12 months of EMA warning were 2763. 12 months before EMA Warning they were 2935. Twelve months after EMA Warning they were 3419. Between 12 months till 21 months they were 3174. Musculoskeletal disorders were respectively 574 (21% of the total) 21 months before, 558 (19%) 12 months before, 1048 (31%) after 12 months, 540 (17%) after 21 months of EMA Warning. Nervous system disorders were respectively 606 (22% of the total) 21 months before, 517 (18%) 12 months before, 680 (20%) after 12 months, 560 (18%) after 21 months of EMA Warning (respectively OR 1,16 95%CI 1,10 -1,22, P 0,12 ; OR 0,76 95%CI 0,69-0,83, P 0,27 ; OR 1,01 95%CI 0,96-1,06 P 0,05). Our analysis clearly showed no significant differences before and after EMA warning, opening new insights in the role of the EMA warning in clinical practice.


Trematode life cycles: short is sweet?
Complex life cycles are a hallmark of parasitic trematodes. In several trematode taxa, however, the life cycle is truncated: fewer hosts are used than in a typical three-host cycle, with fewer transmission events. Eliminating one host from the life cycle can be achieved in at least three different ways. Some trematodes show even more extreme forms of life cycle abbreviations, using only a mollusc to complete their cycle, with or without sexual reproduction. The occurrence of these phenomena among trematode families are reviewed here and show that life cycle truncation has evolved independently many times in the phylogeny of trematodes. The hypotheses proposed to account for life-cycle truncation, in addition to the factors preventing the adoption of shorter cycles by all trematodes are also discussed. The study of shorter life cycles offers an opportunity to understand the forces shaping the evolution of life cycles in general.


Quality of Life Assessment in Multiple Sclerosis: Different Perception between Patients and Neurologists.
In recent years, neurologists are noticing that evaluation of multiple sclerosis (MS) patients based on combining relapses, disability progression, and magnetic resonance imaging activity may be insufficient to adequately assess suboptimal responses to available therapy. Inclusion of quality of life (QoL) parameters may contribute to breach this gap. To evaluate agreement levels between doctor and patient perception of QoL in MS. A total of 700 MS patients and 300 neurologists were invited to participate in a cross-sectional study by answering an e-mail questionnaire. The survey collected information on demographical data and included the Short Form questionnaire (SF-36). After completing the questionnaire, patients were given a standard written description of each of the subdomains assessed by SF-36 and asked to identify which three were the most important determinants of their overall health-related QoL. A total of 135 neurologists and 380 MS patients responded the survey. Study population mean age was 42.1 ± 10.5 years, with 61% presenting relapsing-remitting MS. SF-36 results were physical function 68.4 ± 30, physical role limitation 56.8 ± 41.7, vitality 47.6 ± 21.4, pain 71.2 ± 26.1, social function 72.6 ± 28.6, emotional role limitation 63.2 ± 39.8, mental health 60 ± 14.1, and general health 55.8 ± 22. Doctors considered physical function (75%) and physical role limitation (70%) as the most important QoL determinants in MS, followed by emotional role limitation (52%). Patients however, assigned significantly different levels of importance to physical function (58%), and physical role limitation (46%) and considered vitality (52%) more important than their physicians (p < 0.001). Important to note, the results of SF-36 questionnaire were highly correlated with the perception gap between patients and neurologists (r = 0.89; p = 0.0004). Concerns on QoL in MS are different for patients and physicians. It is essential to enhance communication in order to better understand actual patient needs.


Risk factors and histopathological features of breast cancer among women with different menopausal status and age at diagnosis.
Although there are studies that investigate different risk factors and clinicopathological features of breast cancer in women at different age groups and menopausal status, there is a need for studies with larger study populations due to controversial findings. We conducted this study to identify demographic parameters in breast cancer patients and histopathological features of the tumors for different age groups and compare them to demonstrate significant differences, if any. 3325 women diagnosed with breast cancer in Hacettepe University Oncology Hospital Outpatient Clinic between January 1994 and March 2014 were included in this study. Postmenopausal women who were older than 65 were found to have higher number of children, higher rates of oral contraceptive use, greater age at menarche, and have higher rates of first full-time pregnancy before the age of 30. On the other hand, higher rates of grade 3 tumors, advanced lymph node stage, lymphovascular invasion, and triple negative breast cancers were more frequently seen in premenopausal women below the age of 35. Since earlier age at the time of diagnosis is associated with bad prognosis, early diagnosis of breast cancer gains importance in younger women. Implementing targeted screening programs of breast cancer for younger women may become a need in the future. Meanwhile, well-education on risks of breast cancer and regular self-examination for early diagnosis need to be emphasized for the prevention of breast cancer and related diseases in young ages.


Endothelin 1 promotes osteoarthritic cartilage degradation via matrix metalloprotease 1 and matrix metalloprotease 13 induction.
Degradation of the collagenous extracellular matrix by metalloproteases (MMPs) plays an important role in the pathogenesis of osteoarthritis (OA). Recently, it was suggested that endothelin 1 (ET-1), a potent vasoconstrictor, may be involved in MMP regulation. This study investigated the role of ET-1 in OA cartilage degradation. We explored ET-1 expression and synthesis in normal and OA cartilage and synovial membrane by reverse transcription-polymerase chain reaction and immunohistochemistry. MMP-1 and MMP-13 gene expression and protein synthesis were investigated using Northern blotting and enzyme-linked immunosorbent assays. Additionally, ET-1-induced collagenase activity, type II collagen metabolites, and tissue inhibitor of metalloproteases 1 (TIMP-1) protein were evaluated. We found expression and synthesis of ET-1, in situ, in both normal and OA cartilage and synovial membrane. We demonstrated that ET-1 induced gene expression and protein synthesis of both MMP-1 and MMP-13. These enzymes were produced in OA chondrocyte cultures, and the production increased in a dose-dependent manner in the presence of ET-1. In OA cartilage, ET-1 also induced type II collagen-derived neoepitopes concomitantly with an increase in collagenase activity and a decrease in TIMP-1 protein. Our results provide strong evidence of the catabolic role of ET-1 in OA cartilage via MMP-1 and MMP-13 up-regulation. As well, ET-1 increased the net MMP/TIMP balance and secondarily increased collagen degradation. Hence, ET-1 becomes an attractive factor to target in the conception of new therapeutic approaches for OA and other diseases in which MMP-13 and MMP-1 actions are crucial in tissue alteration.


Awake fiberoptic intubation in patients with stenosis of the upper airways: Utility of the laryngeal nerve block.
Awake fiberoptic intubation (AFOI) is mandatory to manage difficult airways. Superior laryngeal nerve block (SLNB) could reduce risks and improve patient comfort. The aim of this study is to assess the procedural comfort of SLNB during AFOI in a population of patients undergoing upper airway oncological surgery. Forty patients were randomized into two groups and were treated with continuous infusion of remifentanil, topic anesthesia and intercricoid block. In the study group (=20), SLNB was performed with lidocaine (L-SLNB); in the control group (n=20) SLNB was performed using saline (S-SLNB). AFOI was more comfortable in the L-SLNB group compared to S-SLNB patients [FOICS ≤ 1 in 18 patients (90%) L-SLNB; 2 (10%) S-SLNB (P <0.001)]. Intubation was faster in L-SLNB (47.45 ±15.38 sec) than S-SLNB (80.15 ±37.91 sec) (p <0.001). The SLNB procedure during AFOI is a safe and comfortable procedure in a population of patients undergoing upper airways surgery. Time to intubation was shorter in L-SLNB than in S-SLNB.


The effect of learning curve on the results of percutaneous transforaminal endoscopic lumbar discectomy.
To demonstrate the correlation of postoperative visual analog scale (VAS) of leg pain and adequacy of disc decompression with the learning curve of the surgeon who performed PTELD. The authors retrospectively reviewed 50 matched criteria patients arranged into 5 groups which were categorized by the period of operation from January 2010 to May 2011 successively. Each patient's preoperative and postoperative VAS of leg pain at 1-week, 3-week, and 6-week follow-up were analyzed and demonstrated the correlation with the learning curve. Additionally, the authors also showed the alteration of thecal sac expansion between the preoperative and the postoperative MRI to demonstrate the learning curve during the different operative period. The VAS of leg pain as well as the mean differences of VAS of leg pain in each groups of patient were improved at each postoperative period follow-up and have a statistically significant improvement at 6-week follow-up. When the authors analyzed the mean differences VAS at pre- and post-operative 6-week follow-up among each groups of patients, it demonstrated that the learning curve had the progressive effect on the result of the operation. Also for the adequacy of disc decompression, the improvement of the thecal sac expansion was established when the amount of surgical volume was increased. The amount of surgical volume in focus of PTELD has an influence in the improvement of the VAS of leg pain and the adequacy of disc decompression. However, the patient selection such as types of disc herniation is also play an important role in accomplishment.


NY-ESO-1-specific immunological pressure and escape in a patient with metastatic melanoma.
During cancer progression, malignant cells may evade immunosurveillance. However, evidence for immunological escape in humans is scarce. We report here the clinical course of a melanoma patient whose initial tumor was positive for the antigens NY-ESO-1, MAGE-C1, and Melan-A. Upon immunization with a recombinant vaccinia/fowlpox NY-ESO-1 construct, the patient experienced a mixed clinical response and spreading of the NY-ESO-1 epitopes in the CD4+ T cell compartment. After NY-ESO-1 protein + CpG immunization, the patient's anti-NY-ESO-1 IgG response increased. Over the following years, progressing lesions were resected and found to be NY-ESO-1-negative while being positive for MAGE-C1, Melan-A, and MHC-I. The fatal, inoperable brain metastasis was analyzed after his death and also proved to be NY-ESO-1-negative, while being positive for MAGE-C1 and Melan-A, as well as MHC-I. We propose that cancer control and cancer escape in this patient were governed by NY-ESO-1-specific immunological pressure. Our findings provide evidence for the existence of immunoediting and immunoescape in this cancer patient.


Hormonal studies in Klinefelter's syndrome.
Some aspects of the hormonal abnormalities of Klinefelter's syndrome have been studied in nineteen patients. As a group the plasma production rate, the total and free levels of testosterone, and the metabolic clearance rates of testosterone and oestradiol were low. Plasma oestradiol, LH and FSH levels were elevated and there was increased peripheral conversion of testosterone to oestradiol. The production rates of oestradiol and the binding capacities of the sex steroid binding globulin were normal. There were fluctuations in the blood levels of LH, FSH, testosterone and oestradiol, but these appeared to be less marked than in healthy men. Both LH and FSH levels were suppressed by acute or prolonged testosterone administration and there was no evidence for a differential effect on LH. It is suggested that the threshold for suppression of LH and FSH is increased in hypergonadotrophic states. Although no statistically significant relationships were found between the hormonal and clinical abnormalities of the syndrome it is probable that the hyperoestrogenism and androgen deficiency are linked to the development of the signs of feminization and hypogonadism.


Preparation of Clindamycin Hydrochloride Loaded De-Esterified Low-Methoxyl Mango Peel Pectin Film Used as a Topical Drug Delivery System.
In this study, we aimed to develop a low-mexthoxyl pectin (LMP) from mango peel pectin through a de-esterification method for use as a film forming agent. The prepared de-esterified pectin (DP) was compared to commercial LMP (cLMP) which possessed a 29% degree of esterification (DE). Mango peel pectin was extracted from ripe Nam Dokmai mango peel using the microwave-assisted extraction method. Pectin derived from the mango peel was classified as a high mexthoxyl pectin (79% DE) with 75% of galacturonic acid (GalA) content. A de-esterification experiment was designed by central composite design to plot the surface response curve. Our prepared DP was classified as LMP (DE 29.40%) with 69% GalA. In addition, the Fourier-transform infrared spectrophotometer (FTIR) spectra of the DP were similar to cLMP and the pectin backbone was not changed by the de-esterification process. Strikingly, the cLMP and DP films showed non-significant differences between their physical properties (p > 0.05) with respect to the puncture strength (13.72 N/mm2 and 11.13 N/mm2 for the cLMP and DP films, respectively), percent elongation (2.75% and 2.52% for the cLMP and DP films, respectively), and Young's modulus (67.69 N/mm2 and 61.79 N/mm2 for the cLMP and DP films, respectively). The de-esterified pectin containing clindamycin HCl (DPC) and low-methoxyl pectin containing clindamycin HCl (cLMPC) films demonstrated 93.47% and 98.79% of drug loading content. The mechanical properties of the cLMPC and DPC films were improved possibly due to their crystal structures and a plasticizing effect of clindamycin HCl loaded into the films. The DPC film exhibited a drug release profile similar to that of the cLMPC film. Our anti-bacterial test of the films found that the cLMPC film showed 41.11 and 76.30 mm inhibitory clear zones against Staphylococcus aureus and Cutibacterium acnes, respectively. The DPC film showed 40.78 and 74.04 mm clear zones against S. aureus and C. acnes, respectively. The antibacterial activities of the cLMPC and DPC films were not significantly different from a commercial clindamycin solution. The results of this study suggest that mango peel pectin can be de-esterified and utilized as an LMP and the de-esterified pectin has the potential for use as a film forming agent, similar to cLMP. In addition, the remarkable use of de-esterified mango peel pectin to prepare films, as shown by our study, holds a great promise as an alternative material for anti-bacterial purposes.


Field-Induced Slow Magnetic Relaxation in a Mononuclear Manganese(III)-Porphyrin Complex.
We report on a novel manganese(III)-porphyrin complex with the formula [Mn(III) (TPP)(3,5-Me2 pyNO)2 ]ClO4 ⋅CH3 CN (2; 3,5-Me2 pyNO=3,5-dimethylpyridine N-oxide, H2 TPP=5,10,15,20-tetraphenylporphyrin), in which the Mn(III) ion is six-coordinate with two monodentate 3,5-Me2 pyNO molecules and a tetradentate TPP ligand to build a tetragonally elongated octahedral geometry. The environment in 2 is responsible for the large and negative axial zero-field splitting (D=-3.8 cm(-1) ), low rhombicity (E/|D|=0.04) of the high-spin Mn(III) ion, and, ultimately, for the observation of slow magnetic-relaxation effects (Ea =15.5 cm(-1) at H=1000 G) in this rare example of a manganese-based single-ion magnet (SIM). Structural, magnetic, and electronic characterizations were carried out by means of single-crystal diffraction studies, variable-temperature direct- and alternating-current measurements and high-frequency and -field EPR spectroscopic analysis followed by quantum-chemical calculations. Slow magnetic-relaxation effects were also observed in the already known analogous compound [Mn(III) (TPP)Cl] (1; Ea =10.5 cm(-1) at H=1000 G). The results obtained for 1 and 2 are compared and discussed herein.


Identifying the mechanism of missingness for unspecified diabetic retinopathy disease severity in the electronic health record: an IRIS® Registry analysis.
Observational studies of diabetic retinopathy (DR) using electronic health record data often determine disease severity using International Classification of Disease (ICD) codes. We investigated the mechanism of missingness for DR severity based on ICD coding using the American Academy of Ophthalmology IRIS® Registry. We included all patient encounters in the registry with a DR ICD-9 or ICD-10 code between January 1, 2014 and June 30, 2021. Demographic, clinical, and practice-level characteristics were compared between encounters with specified and unspecified disease severity. Practices were divided into quartiles based on the proportion of clinical encounters with unspecified DR severity. Encounters with unspecified disease severity were associated with significantly older patient age, better visual acuity, and lower utilization of ophthalmic procedures. Higher volume practices and retina specialist practices had lower proportions of clinical encounters with unspecified disease severity. Results strongly suggest that DR disease severity related to ICD coding is missing not at random.


Enamel defects in children with coeliac disease.
This was to investigate the prevalence of enamel developmental defects in a group of children with a history of coeliac disease. A study group of children attending the Dept. Paediatrics (Leeds General Infirmary), born between 1985 and 1986 and subsequently diagnosed and treated for coeliac disease (CD) were recruited. A group of age/sex-matched children attending the Paediatric Dentistry department were used as a control group (Cont). Examinations were carried out for enamel defects and opacities (DDE index), dmf, dmfs, DMF and DMFS (BASCD method), and a full medical and dental history were obtained. Significantly more children in the CD group had a greater number of enamel defects than controls for both primary (p=<0.02) and permanent (p=<0.001) dentitions. Opacities in both primary and permanent teeth were statistically significantly greater in the CD group than controls (p=<0.04 and p=<0.001 respectively). Dental caries in both primary and permanent dentitions was less in the CD group compared with the control group of children. Coeliac disease was associated with an increased prevalence of developmental enamel defects.


Nodal metastasis in cervical cancer occurs in clearly delineated fields of immune suppression in the pelvic lymph catchment area.
In cervical cancer, high frequencies of regulatory T cells (Tregs) and immunosuppressive PD-L1+CD14+ antigen-presenting cells dominate the microenvironment of tumor-positive lymph nodes (LN+). It is unknown whether this is restricted to LN+ or precedes metastasis, emanating from the primary tumor and spreading through tumor-draining lymph nodes (TDLNs). To investigate immunosuppression in the lymphatic basin of cervical tumors, all dissected TDLNs of five cervical cancer patients (in total 9 LN+ and 74 tumor-negative lymph nodes (LN-)) were analyzed for FoxP3+ Tregs, CD8+ T cells, HLA-DR+- and PD-L1+ myeloid cells by immunohistochemistry.Tregs and PD-L1+ cells were found to form an immunosuppressive cordon around metastatic tumor cells. Importantly, whereas high HLA-DR+- and PD-L1+ cell rates were strongly associated with LN+, elevated Treg levels and decreased CD8+ T cell/Treg ratios were found similar in LN+ and adjacent LN-, as compared to LN- at more distant anatomical localizations. These data suggest that delineated fields of Treg-associated immune suppression in anatomically co-localized TDLNs enable metastasis by creating metastatic niches. This may be of importance for decision-making regarding (surgical) intervention in cervical cancer. Future efforts should include the implementation of immunotherapeutic regimens to overcome this immune suppression, establish loco-regional control and halt systemic tumor spread.


Sonography of the medial and lateral tendons and ligaments of the knee: the use of bony landmarks as an easy method for identification.
Our purpose was to describe the use of bony landmarks in the evaluation of the medial and lateral ligaments and tendons of the knee on sonography and to evaluate the value of this approach in healthy volunteers. Anatomic slices obtained in cadaveric specimens were inspected for the presence of bony landmarks on the medial and lateral aspects of the knee. Then sonography was performed on 40 knees of 20 healthy volunteers by two musculoskeletal radiologists who independently rated the visualization of bony landmarks and adjacent ligaments and tendons on a 5-point grading scale. Bony landmarks on the lateral aspect of the knee include Gerdy's tubercle on the tibia and the sulcus for the popliteal tendon on the femur. Landmarks on the medial aspect of the knee include the medial epicondyle on the femur and the sulcus for the semimembranosus tendon on the tibia. Visualization of all landmarks was rated in the good to excellent range, and agreement between observers ranged from 92.5% to 100%. Bony landmarks can be identified in healthy adults on the medial and lateral aspects of the knee and may serve as reference points for identification of most medial and lateral tendons and ligaments.


Resistance of streptococcus pneumoniae to antimicrobials in São Paulo, Brazil: clinical features and serotypes.
To study resistance to antimicrobials, serotypes and clinical features of S. pneumoniae in S. Paulo, Brazil, 50 patients with a positive culture were evaluated: 7 were considered carriers and 43 had pneumococcal infections. Pneumonia and meningitis were the most common infections. Mortality was 34% and underlying diseases were present in 70%. Relative resistance to penicillin occurred in 24% and complete resistance was not detected. Resistance to tetracycline was 32% and to sulfamethoxazole/trimethoprim 32%; one strain had intermediate susceptibility to erythromycin; no resistance was present for chloramphenicol, rifampin or vancomycin. Resistance to at least one of the drugs tested occurred in 62%. Results by the E-test for penicillin were similar to those by the agar dilution method. There were 24 different serotypes and 74% of the strains belonged to the 23-valent vaccine including all the penicillin-resistant strains. In this study S. pneumoniae caused severe infections and presented a high resistance rate to commonly used antimicrobials. Routine surveillance of resistance and the use of vaccination, as well as the restriction of inappropriate use of antimicrobials, are recommended in São Paulo, Brazil.


Lenvatinib for poorly differentiated carcinoma of the anterior mediastinum.
We describe a Case of a 74-year-old Japanese man with poorly differentiated carcinoma of the anterior mediastinum. The patient underwent anterior mediastinal tumor resection through median sternotomy. The tumor, 7.0 × 5.0 cm, had invaded surrounding tissues (pericardium, right lung, right and left brachiocephalic veins, and superior vena cava). Complete resection of the tumor was not performed. One month after the operation, the patient developed multiple pulmonary metastases, right pleural dissemination, and carcinomatous pleurisy. He was treated with lenvatinib, a novel multi-kinase inhibitor, to which the metastasis responded favorably. This case reports for the first time the clinical usefulness of lenvatinib for poorly differentiated carcinoma of the anterior mediastinum. Management of side effects by several methods, including suspending use of medication on weekends (called a weekends-off strategy), is another strong argument to continue lenvatinib administration.


Differential coexpression analysis using microarray data and its application to human cancer.
Microarrays have been used to identify differential expression of individual genes or cluster genes that are coexpressed over various conditions. However, alteration in coexpression relationships has not been studied. Here we introduce a model for finding differential coexpression from microarrays and test its biological validity with respect to cancer. We collected 10 published gene expression datasets from cancers of 13 different tissues and constructed 2 distinct coexpression networks: a tumor network and normal network. Comparison of the two networks showed that cancer affected many coexpression relationships. Functional changes such as alteration in energy metabolism, promotion of cell growth and enhanced immune activity were accompanied with coexpression changes. Coregulation of collagen genes that may control invasion and metastatic spread of tumor cells was also found. Cluster analysis in the tumor network identified groups of highly interconnected genes related to ribosomal protein synthesis, the cell cycle and antigen presentation. Metallothionein expression was also found to be clustered, which may play a role in apoptosis control in tumor cells. Our results show that this model would serve as a novel method for analyzing microarrays beyond the specific implications for cancer.


Ethics and professionalism among community health workers in Tamil Nadu, India: A qualitative study.
Community health workers (CHW) are the backbone of the public health system in developing countries. Little is known about the practice of ethics and professionalism in their work. This study was conducted to explore the experiential wisdom of ethics and professionalism among CHWs in Tamil Nadu. We conducted a qualitative study among 125 CHWs in six districts of Tamil Nadu. We found that the CHWs went beyond the call of their duty to do good to the community. Their conceptualization of autonomy ranged from shared to full paternalistic decision making. The CHWs were sensitive to issues of privacy and confidentiality, but the discussion on these topics were limited. They reflected the societal norms of gender, class, and caste hierarchies in their work. They had to work amidst difficult power struggles and had their own innovative strategies to subvert power. In conclusion, there is a need for framing a code of ethics and professionalism for CHWs and training in ethics and professionalism for them to help them effectively deliberate on ethical issues.


Recovery from traumatic brain injury (TBI) is Nociceptin/Orphanin FQ peptide (NOP) receptor genotype-, sex-, and injury severity-dependent.
Traumatic brain injury (TBI) is a leading cause of death and disability in the United States and survivors often experience mental and physical health consequences that reduce quality of life. We previously reported that blockade of the nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor reduced tissue damage markers produced by blast TBI. The goal of this study was to determine the extent to which N/OFQ and NOP receptor levels change following mild (mTBI) and moderate TBI (modTBI) and whether the absence of the NOP receptor attenuates TBI-induced sequelae. Male and female NOP receptor knockout (KO) or wild-type (WT) rats received craniotomy-only (sham), or craniotomy plus mild (mTBI), or moderate TBI (modTBI) impact to the left cerebral hemisphere. Neurological and vestibulomotor deficits, and nociceptive hyperalgesia and allodynia found in WT male and female rats following mTBI and modTBI were greatly reduced or absent in NOP receptor KO rats. NOP receptor levels increased in brain tissue from injured males but remained unchanged in females. NF-L and GFAP expression were reduced in NOP receptor KO rats compared to WT following TBI. Levels of N/OFQ in injured brain tissue correlated with neurobehavioral outcomes and GFAP in WT males, but not with KO male or WT and KO female rats. This study reveals a significant contribution of the N/OFQ-NOP receptor system to TBI-induced deficits and suggests that the NOP receptor should be regarded as a potential therapeutic target for TBI. Significance Statement This study revealed that NOP receptor KO animals experienced fewer TBI-induced deficits than their WT counterparts in a sex- and injury severity-dependent manner, suggesting that NOP receptor antagonists may be a potential therapy for TBI.


Current clinical management of Legionnaires' disease.
Legionella pneumophila is increasingly recognized as a cause of both sporadic and epidemic community-acquired pneumonia. Clinical manifestations of Legionnaires' disease are not specific and current diagnostic scores are of limited use. Urinary antigen detection is an effective test for rapid diagnosis of infection caused by L. pneumophila serogroup 1. Improved outcomes regarding the time to defervescence, development of complications and length of stay, have been recently observed for patients treated with levofloxacin monotherapy. Current case-fatality rates for hospitalized patients with community-acquired Legionella pneumonia are lower than those traditionally reported for this infection. Effective preventive strategies are needed.


Identification of the metabolites of episesamin in rat bile and human liver microsomes.
Episesamin is an isomer of sesamin, resulting from the refining process of non-roasted sesame seed oil. Episesamin has two methylendioxyphenyl groups on exo and endo faces of the bicyclic skeleton. The side methylendioxyphenyl group was metabolized by cytochrome-P450. Seven metabolites of episesamin were found in rat bile after treatment with glucuronidase/arylsulfatase and were identified using NMR and MS. The seven metabolites were (7α,7'β,8α,8'α)-3,4-dihydroxy-3',4'-methylenedioxy-7,9':7',9-diepoxylignane (EC-1-1), (7α,7'β,8α,8'α)-3,4-methylenedioxy-3',4'-dihydroxy-7,9':7',9-diepoxylignane (EC-1-2) and (7α,7'β,8α,8'α)-3,4:3',4'-bis(dihydroxy)-7,9':7',9-diepoxylignane (EC-2), (7α,7'β,8α,8'α)-3-methoxy-4-hydroxy-3',4'-methylenedioxy-7,9':7',9-diepoxylignane (EC-1m-1), (7α,7'β,8α,8'α)-3,4-methylenedioxy-3'-methoxy-4'-hydroxy-7,9':7',9-diepoxylignane (EC-1m-2), (7α,7'β,8α,8'α)-3-methoxy-4-hydroxy-3',4'-dihydroxy-7,9':7',9-diepoxylignane (EC-2m-1) and (7α,7'β,8α,8'α)-3,4-dihydroxy-3'-methoxy-4'-hydroxy-7,9':7',9-diepoxylignane (EC-2m-2). EC-1-1, EC-1-2 and EC-2 were also identified as metabolites of episesamin in human liver microsomes. These results suggested that similar metabolic pathways of episesamin could be proposed in rats and humans.


Celebrating Soft Matter's 10th anniversary: stimuli-responsive Pickering emulsion polymerized smart fluids.
The Pickering emulsion process is an important and interesting way of forming hybrid soft matter particles stabilized by solid particles as surfactants instead of the extensive use of conventionally available organic surfactant molecules. This Highlight briefly reviews stimuli-responsive polymer/inorganic hybrid materials fabricated by Pickering emulsion polymerization along with the rheological characteristics of their electrorheological and magnetorheological smart fluids under electric and magnetic fields, respectively.