Coordination polymers and hydrogen-bonded assemblies of 2,2'-[2,5-bis(carboxymethoxy)-1,4-phenylene]diacetic acid with ammonium, lanthanum and zinc cations.
We report the synthesis of the 2,2'-[2,5-bis(carboxymethoxy)-1,4-phenylene]diacetic acid (TALH(4)) ligand and the structures of its adducts with ammonium, namely diammonium 2,2'-[2,5-bis(carboxymethyl)-1,4-phenylenedioxy]diacetate, 2NH(4)(+).C(14)H(12)O(10)(2-), (I), lanthanum, namely poly[[aquabis[mu(4)-2,2'-(2-carboxylatomethyl-5-carboxymethyl-1,4-phenylenedioxy)diacetato]dilanthanum(III)] monohydrate], {[La(2)(C(14)H(11)O(10))(2)(H(2)O)].H(2)O}(n), (II), and zinc cations, namely poly[[{mu(4)-2,2'-[2,5-bis(carboxymethyl)-1,4-phenylenedioxy]diacetato}zinc(II)] trihydrate], {[Zn(C(14)H(12)O(10))].3H(2)O}(n), (III), and poly[[diaqua(mu(2)-4,4'-bipyridyl){mu(4)-2,2'-[2,5-bis(carboxymethyl)-1,4-phenylenedioxy]diacetato}dizinc(II)] dihydrate], {[Zn(2)(C(14)H(10)O(10))(C(10)H(8)N(2))(H(2)O)(2)].2H(2)O}(n), (IV), the formation of all four being associated with deprotonation of TALH(4). Adduct (I) is a diammonium salt of TALH(2)(2-), with the ions located on centres of crystallographic inversion. Its crystal structure reveals a three-dimensional hydrogen-bonded assembly of the component species. Reaction of TALH(4) with lanthanum trinitrate hexahydrate yielded a two-dimensional double-layer coordination polymer, (II), in which the La(III) cations are nine-coordinate. With zinc dinitrate hexahydrate, TALH(4) forms 1:1 two-dimensional coordination polymers, in which every Zn(II) cation is linked to four neighbouring TALH(2)(2-) anions and each unit of the organic ligand is coordinated to four different tetrahedral Zn(II) cation connectors. The crystal structure of this compound accommodates molecules of disordered water at the interface between adjacent polymeric layers to give (III), and it has been determined with low precision. Another polymer assembly, (IV), was obtained when zinc dinitrate hexahydrate was reacted with TALH(4) in the presence of an additional 4,4'-bipyridyl ligand. In the crystal structure of (IV), the bipyridyl and TAL(4-) entities are located on two different inversion centres. The ternary coordination polymers form layered arrays with corrugated surfaces, with the Zn(II) cation connectors revealing a tetrahedral coordination environment. The two-dimensional polymers in (II)-(IV) are interconnected with each other by hydrogen bonds involving the metal-coordinated and noncoordinated molecules of water. TALH(4) is doubly deprotonated, TALH(2)(2-), in (I) and (III), triply deprotonated, viz. TALH(3-), in (II), and quadruply deprotonated, viz. TAL(4-), in (IV). This report provides the first structural characterization of TALH(4) (in deprotonated form) and its various supramolecular adducts. It also confirms the potential utility of this tetraacid ligand in the formulation of coordination polymers with metal cations.


Phalangeal morphology of Shanghuang fossil primates.
Here, we describe hundreds of isolated phalanges attributed to middle Eocene fossil primates from the Shanghuang fissure-fillings from southern Jiangsu Province, China. Extending knowledge based on previous descriptions of postcranial material from Shanghuang, this sample of primate finger and toe bones includes proximal phalanges, middle phalanges, and over three hundred nail-bearing distal phalanges. Most of the isolated proximal and middle phalanges fall within the range of small-bodied individuals, suggesting an allocation to the smaller haplorhine primates identified at Shanghuang, including eosimiids. In contrast to the proximal and middle phalanges from Shanghuang, there are a variety of shapes, sizes, and possible taxonomic allocations for the distal phalanges. Two distal phalangeal morphologies are numerically predominant at Shanghuang. The sample of larger bodied specimens is best allocated to the medium-sized adapiform Adapoides while the smaller ones are allocated to eosimiids on the basis of the commonality of dental and tarsal remains of these taxa at Shanghuang. The digit morphology of Adapoides is similar morphologically to that of notharctines and cercamoniines, while eosimiid digit morphology is unlike living anthropoids. Other primate distal phalangeal morphologies at Shanghuang include grooming "claws" as well as specimens attributable to tarsiids, tarsiiforms, the genus Macrotarsius, and a variety of adapiforms. One group of distal phalanges at Shanghuang is morphologically indistinguishable from those of living anthropoids. All of the phalanges suggest long fingers and toes for the fossil primates of Shanghaung, and their digit morphology implies arboreality with well-developed digital flexion and strong, grasping hands and feet.


Exhaled breath analysis for the diagnosis and assessment of endoluminal gastrointestinal diseases.
Investigation of gastrointestinal diseases is often invasive to the patient and costly. Exhaled breath analysis of volatile organic compounds (VOCs) may provide a noninvasive diagnostic tool to allow the assessment and stratification of risk. The aim of this review was to evaluate the current role of VOC breath analysis in the diagnosis and assessment of endoluminal gastrointestinal disease. Medline, Embase, Cochrane, trial registries, conference proceedings, and reference lists were searched for relevant diagnostic studies. Gastrointestinal diseases studied included inflammatory bowel disease (IBD), celiac disease, and colorectal and gastroesophageal cancer. Eleven studies comprising 934 patients were included. IBD was associated with an increase in breath alkanes compared with controls, and the degree of increase was correlated with disease activity in some studies. Colorectal cancer could be distinguished from controls on the basis of VOC profiling; however, the metabolites analyzed varied between studies preventing the generation of a reproducible diagnostic model. In isolated cohort studies, significant differences in the VOC profiles from exhaled breath of patients with gastroesophageal cancer were observed, suggesting that this may have a future role as a noninvasive diagnostic test. Assessment of the cumulative level of surrogate validity for disease-specific breath analysis suggested that the best evidence is for esophagogastric cancer followed by colorectal cancer and IBD. Exhaled breath analysis of VOCs does provide a potential noninvasive tool to determine risk of gastrointestinal disease. Future areas for research include: standardizing breath tests and improving mechanistic understanding of the VOCs associated with specific gastrointestinal disease states in large multicenter population studies.


Correction: Natural polyenic macrolactams and polycyclic derivatives generated by transannular pericyclic reactions: optimized biogenesis challenging chemical synthesis.
Correction for 'Natural polyenic macrolactams and polycyclic derivatives generated by transannular pericyclic reactions: optimized biogenesis challenging chemical synthesis' by Rosana Alvarez et al., Nat. Prod. Rep., 2021, DOI: 10.1039/d0np00050g.


[Clinical effects of vacuum sealing drainage in the treatment of alkali burn wounds].
Objective: To preliminarily observe the clinical effects of vacuum sealing drainage (VSD) in the treatment of alkali burn wounds. Methods: From June 2016 to March 2020, 60 male patients with alkali burns who met the inclusion criteria and hospitalized in the Affiliated Hospital of Jiangnan University were recruited in this prospectively randomized control study. According to the random number table, silver sulfadiazine group and VSD group were both allocated with 30 patients, aged (36±8) and (35±10) years respectively; with total burn area of (7.2±2.0) % and (8.5±3.0) % total body surface area respectively. After admission, patients in silver sulfadiazine group were treated with conventional silver sulfadiazine dressing change once a day after debridement; patients in VSD group were given continuous VSD treatment after debridement, with the negative pressure setting at -10.67 kPa, and the negative pressure materials were replaced every 6 to 8 days. On treatment day 1, 4, and 7, the exudate from the wounds of patients in silver sulfadiazine group and the wound drainage fluid of patients in VSD group were collected, the pH value was measured by a portable pH meter, and the volume of exudate/drainage fluid was measured. After 7, 14, and 21 days of treatment, the wound healing rates of patients were calculated in the two groups. Before treatment and 7 days after treatment, venous blood was collected from the patients in the two groups to detect the serum level of tumor necrosis factor α (TNF-α) and interleukin 8 (IL-8). Within treatment day 14, Visual Analogue Scale was used to assess the pain score of patients in the two groups during each time of dressing change. The medical costs and discharge satisfaction scores of patients in the two groups were recorded. Data were statistically analyzed with analysis of variance for repeated measurement, t test, and Bonferroni correction. Results: (1) On treatment day 1, 4, and 7, the pH values of the drainage fluid of patients in VSD group were 9.75±0.59, 9.01±0.46, and 8.13±0.28, respectively, which were significantly higher than 9.35±0.62, 8.18±0.18, and 7.58±0.09 of exudate of patients in silver sulfadiazine group (t=2.03, 6.80, 7.56, P<0.05 or P<0.01). On treatment day 1 and 4, the volumes of drainage fluid of patients in VSD group were (553±83) and (239±65) mL respectively, which were significantly higher than (440±77) and (175±49) mL of exudate of patients in silver sulfadiazine group (t=3.44, 2.24, P<0.05). On treatment day 7, the volume of drainage fluid of patients in VSD group was (21±8) mL, which was significantly lower than (149±44) mL of exudate of patients in silver sulfadiazine group (t=-12.61, P<0.01). (2) After 7, 14, and 21 days of treatment, the wound healing rates of patients in VSD group were (39±6) %, (74±10) %, and (92±3) %, respectively, which were significantly higher than (25±3) %, (59±6) %, and (77±6) % in silver sulfadiazine group (t=7.07, 5.59, 7.09, P<0.01). (3) Before treatment, the serum levels of TNF-α and IL-8 of patients in the two groups were similar. After 7 days of treatment, the serum levels of TNF-α and IL-8 of patients in VSD group were significantly lower than those in silver sulfadiazine group (t=-8.75, -8.04, P<0.01). (4) The pain score during dressing change and medical cost of patients in VSD group were significantly lower than those in silver sulfadiazine group (t=-4.28, -7.56, P<0.01), while the discharge satisfaction score of patients in VSD group was significantly higher than that in silver sulfadiazine group (t=10.91, P<0.05). Conclusions: The application of VSD technology in clinical alkali burn wounds can effectively promote the removal of residual lye, alleviate the further damage of lye to skin tissue, shorten the wound healing time, effectively remove inflammatory mediators, reduce the pain of dressing change, decrease the total cost of treatment, and enhance satisfaction of patient.


Analysis of Acrolein Exposure Induced Pulmonary Response in Seven Inbred Mouse Strains and Human Primary Bronchial Epithelial Cells Cultured at Air-Liquid Interface.
Acrolein is a major component of environmental pollutants, cigarette smoke, and is also formed by heating cooking oil. We evaluated the interstrain variability of response to subchronic inhalation exposure to acrolein among inbred mouse strains for inflammation, oxidative stress, and tissue injury responses. Furthermore, we studied the response to acrolein vapor in the lung mucosa model using human primary bronchial epithelial cells (PBEC) cultured at an air-liquid interface (ALI) to evaluate the findings of mouse studies. Female 129S1/SvlmJ, A/J, BALB/cByJ, C3H/HeJ, C57BL/6J, DBA/2J, and FVB/NJ mice were exposed to 1 part per million (ppm) acrolein or filtered air for 11 weeks. Total cell counts and protein concentrations were measured in bronchoalveolar lavage (BAL) fluid to assess airway inflammation and membrane integrity. PBEC-ALI models were exposed to acrolein vapor (0.1 and 0.2 ppm) for 30 minutes. Gene expression of proinflammatory, oxidative stress, and tissue injury-repair markers was assessed (cut off: ≥2 folds; p < 0.05) in the lung models. Total BAL cell numbers and protein concentrations remained unchanged following acrolein exposure in all mouse strains. BALB/cByJ, C57BL/6J, and 129S1/SvlmJ strains were the most affected with an increased expression of proinflammatory, oxidative stress, and/or tissue injury markers. DBA/2J, C3H/HeJ, A/J, and FVB/NJ were affected to a lesser extent. Both matrix metalloproteinase 9 (Mmp9) and tissue inhibitor of metalloproteinase 1 (Timp1) were upregulated in the strains DBA/2J, C3H/HeJ, and FVB/NJ indicating altered protease/antiprotease balance. Upregulation of lung interleukin- (IL-) 17b transcript in the susceptible strains led us to investigate the IL-17 pathway genes in the PBEC-ALI model. Acrolein exposure resulted in an increased expression of IL-17A, C, and D; IL-1B; IL-22; and RAR-related orphan receptor A in the PBEC-ALI model. The interstrain differences in response to subchronic acrolein exposure in mouse suggest a genetic predisposition. Altered expression of IL-17 pathway genes following acrolein exposure in the PBEC-ALI models indicates that it has a central role in chemical irritant toxicity. The findings also indicate that genetically determined differences in IL-17 signaling pathway genes in the different mouse strains may explain their susceptibility to different chemical irritants.


Induction of Anoikis in Human Colorectal Cancer Cells by Fucoxanthinol.
Fucoxanthin (Fx), one of the major xanthophylls in brown algae, is known to be effective for colorectal cancer (CRC) chemoprevention through inhibiting cell growth, cell cycle and caspase activation. Recently, we observed fucoxanthinol (FuOH), an anti-cancer active metabolite of Fx, treatment of human CRC cells resulted in plenty of living floating cells several hours after exposure, and induced apoptosis. In the present study, we investigated whether FuOH induced anchorage-dependent apoptosis, that is "anoikis", along with integrin signal suppression in human CRC cells. We found that cells exposed to 2.5 μM FuOH clearly showed anti-proliferative and apoptotic effects to DLD-1 cells, human CRC cells. FuOH treatment of DLD-1 cells led to an increase in anoikis-like changes represented by Calcein AM negative/ethidium homodimer-1 positive cell and living floating cells. Moreover, FuOH decreased FAK activation, and altered integrin β1 expression and distribution after 6 h treatment. After 24 h, the cells decreased PPARγ expression and Akt activation and increased integrin β1 expression. Our findings suggested that FuOH can induce anoikis in CRC cells through suppression of integrin signals in human CRC cells.


Janus Fibrous Mats Based Suspended Type Evaporator for Salt Resistant Solar Desalination and Salt Recovery.
Solar desalination has been recognized as an emerging strategy for solving the pressing global freshwater crisis. However, salt crystallization at the photothermal interface frequently causes evaporator failure. In addition, arbitrary discharge of concentrated brine produced during desalination results in potential ecological impacts as well as wastage of valuable minerals. In the present work, a suspended-type evaporator (STEs) constructed using Janus fibrous mats is reported. The fibrous structure wicks brine to the evaporation layer and the salt gets confined in the evaporation layer until crystallization for zero liquid discharge due to the suspended design. Enhanced evaporation is observed because STEs have an additional low-resistance vapor escape path directly from the evaporation layer to the atmosphere compared to traditional floating Janus evaporators. Moreover, owing to the drastically different wettability on both sides, the evaporator allows salt crystallization only on the hydrophilic bottom layer, thus eliminating salt accumulation at the hydrophobic photothermal interface. With this unique structural design, the proposed evaporator not only maintains a high evaporation rate of 1.94 kg m-2 h-1 , but also demonstrates zero liquid discharged salt resistance and ideal recovery of the mineral in brine.


Recurrent delayed immune-related pneumonitis after immune-checkpoint inhibitor therapy for advanced osteosarcoma.
Introduction: The case of a patient who developed recurrent delayed immune-related pneumonitis (checkpoint inhibitor pneumonitis [CIP]) after immune checkpoint inhibitor (ICI) therapy for advanced osteosarcoma treatment is presented. Case summary: A 25-year-old female patient with metastatic osteosarcoma was treated with atezolizumab. Grade 2 pneumonitis developed three times in the first two years. Treatment was discontinued after recovery from the last episode of pneumonitis, which was complicated with secondary spontaneous pneumothorax. 2 years after discontinuation of immunotherapy, the patient again developed CIP. Pneumonitis symptoms were regressed with oral steroid therapy during follow-up and a stable disease response continued. Conclusion: Immunotherapy can cause recurrent CIP at any time during the treatment period or after discontinuation of treatment.


The role of brain-derived neurotrophic factor in comorbid depression: possible linkage with steroid hormones, cytokines, and nutrition.
Increasing evidence demonstrates a connection between growth factor function (including brain-derived neurotrophic factor, BDNF), glucocorticoid levels (one of the steroid hormones), and the pathophysiology of depressive disorders. Because both BDNF and glucocorticoids regulate synaptic function in the central nervous system, their functional interaction is of major concern. Interestingly, alterations in levels of estrogen, another steroid hormone, may play a role in depressive-like behavior in postpartum females with fluctuations of BDNF-related molecules in the brain. BDNF and cytokines, which are protein regulators of inflammation, stimulate multiple intracellular signaling cascades involved in neuropsychiatric illness. Pro-inflammatory cytokines may increase vulnerability to depressive symptoms, such as the increased risk observed in patients with cancer and/or autoimmune diseases. In this review, we discuss the possible relationship between inflammation and depression, in addition to the cross-talk among cytokines, BDNF, and steroids. Further, since nutritional status has been shown to affect critical pathways involved in depression through both BDNF function and the monoamine system, we also review current evidence surrounding diet and supplementation (e.g., flavonoids) on BDNF-mediated brain functions.


Behavioral approach in ADHD: testing a motivational dysfunction hypothesis.
Etiological models of attention-deficit hyperactivity disorder (ADHD) increasingly support the role of a motivational dysfunction pathway, particularly for hyperactive-impulsive symptoms. Overactive behavioral approach tendencies are implicated among these motivational accounts. However, other externalizing disorder symptoms, such as the psychopathy dimension, are also associated with behavioral approach and frequently co-occur with ADHD. The current study tested the hypothesis that behavioral approach is differentially associated with hyperactive-impulsive ADHD and psychopathy symptoms. A sample of young adults ( n = 220) completed self-report measures assessing behavioral approach and inhibition, ADHD symptoms, and psychopathy symptoms. Structural equation analyses supported the hypothesis that behavioral approach predicts hyperactive-impulsive ADHD symptoms while considering symptom overlap with psychopathy symptoms. These findings support motivational accounts that behavioral approach tendencies are predictive of ADHD symptoms and address concerns about externalizing comorbidity. Implications for ADHD etiology are discussed.


Implantation of Covered Stent for Coarctation of the Aorta and Secondary Hypertension in Adolescents-Case Report.
Coarctation of the aorta represents a narrowing of the thoracic aorta. Hypertensive patients with blood pressure differences ≥20 millimetres of mercury have an indication for surgical or interventional treatment. Implantation of a covered stent became the preferred therapy for the management of this pathology in adolescents/adults. We report the case of a 14-year-old male sportsman, who presented in the emergency room with headache, dizziness, and tinnitus. The clinical exam revealed blood pressure differences between the upper and lower limbs of up to 50 mmHg. Based on the clinical and paraclinical data, we established the diagnosis of coarctation of the aorta and severe secondary arterial hypertension. The case was discussed by a multidisciplinary team and accepted for covered stent implantation. The 24 h blood pressure Holter monitoring after the procedure indicated the persistence of stage I arterial hypertension. Coarctation of the aorta is a congenital cardiovascular anomaly with high morbidity and mortality rates. Arterial hypertension, heart failure, and aortic dissection are complications of this pathology, some of them being sometimes direct consequences of secondary hypertension. Periodic cardiology follow up after the procedure is mandatory to assess the hemodynamic response, to identify potential complications, and to stratify the cardiovascular risk.


Modeling the vertical motion of a soft contact lens.
The motion of a soft contact lens in the up-down or vertical (inferior-superior) and in-out (anterior-posterior) directions drives mixing in the post lens tear film. Thus, it is important to obtain an accurate assessment of lens motion. The commonly used experimental technique to measure the vertical motion, video microscopy, only gauges motion during the interblink period. Since most of the eyelid force, which drives the motion, is exerted during the blink, it is reasonable to assume that the majority of the lens motion in the up-down direction takes place during the blink and is, therefore, hidden from view. Thus, experimentally measured values of vertical lens travel are currently underpredicted. In this paper, we use a simple mechanical force balance on the lens to predict its motion in the vertical direction. The forces included in our model are due to the upper and the lower eyelids, gravity, elasticity, and viscous stresses. We input the lens physical parameters, the various tear film thicknesses, and the upper eyelid velocity. Then we integrate a macroscopic force balance to obtain the lens vertical position as a function of time. The proposed model predicts that the downward lens motion during a blink is about 2--3 times the downward motion during the interblink (centration). The up-down motion observable during the interblink period is only a small fraction of the total lens vertical travel.


Weighted mean difference statistics for paired data in the presence of missing values.
Missing data is a common issue in many biomedical studies. Under a paired design, some subjects may have missing values in either one or both of the conditions due to loss of follow-up, insufficient biological samples, etc. Such partially paired data complicate statistical comparison of the distribution of the variable of interest between the two conditions. In this article, we propose a general class of test statistics based on the difference in weighted sample means without imposing any distributional or model assumption. An optimal weight is derived from this class of tests. Simulation studies show that our proposed test with the optimal weight performs well and outperforms existing methods in practical situations. Two cancer biomarker studies are provided for illustration.


[A hybrid method including optimization and force-EMG relationship for predicting muscle force].
A hybrid method based on optimization and force-EMG relationships for predicting muscle force was presented and applied to the flexion movement of upper limb. The results were compared with those from classical optimization and from the method based on force-EMG relationships. The classical optimization can not predict the force of antagonistic muscles. The method based on force-EMG relationships can not satisfy the mechanical equilibrium. The hybrid method overcomes the two disadvantages, but the forces predicted by it fluctuate excessively. Now the hybrid method is just appropriate for use in predicting isometric and isokinetic movements.


Structural and functional characterization of myotoxin I, a Lys49 phospholipase A(2) homologue from Bothrops moojeni (Caissaca) snake venom.
Myotoxin-I (MjTX-I) was purified to homogeneity from the venom of Bothrops moojeni by ion-exchange chromatography on CM-Sepharose. Its molecular weight, estimated by SDS-PAGE, was 13,400 (reduced) or 26, 000 (unreduced). The extinction coefficient (E(1.0 mg/ml)(1.0 cm)) of MjTX-I was 1.145 at lambda = 278 nm, pH 7.0, and its isoelectric point was 8.2 at ionic strength mu = 0.1. When lyophilized and stored at 4 degrees C, dimeric, trimeric, and pentameric forms of the protein were identified by SDS-PAGE. This "heterogeneous" sample could be separated into three fractions by gel filtration on Sephadex G-50. The fractions were analyzed by isoelectric focusing, immunoelectrophoresis, and amino acid composition, which indicated that heterogeneity was the result of different levels of self-association. Protein sequencing indicated that MjTX-I is a Lys49 myotoxin and consists of 121 amino acids (M(r) = 13,669), containing a high proportion of basic and hydrophobic residues. It shares a high degree of sequence identity with other Lys49 PLA(2)-like myotoxins, but shows a significantly lower identity with catalytically active Asp49 PLA(2)s. The three-dimensional structure of MjTX-I was modeled based on the crystal structures of three highly homologous Lys49 PLA(2)-like myotoxins. This model showed that the amino acid substitutions are conservative, and mainly limited to three structural regions: the N-terminal helix, the beta-wing region, and the C-terminal extended random coil. MjTX-I displays local myotoxic and edema-inducing activities in mice, and is lethal by intraperitoneal injection, with an LD(50) value of 8.5 +/- 0.8 mg/kg. In addition, it is cytotoxic to myoblasts/myotubes in culture, and disrupts negatively charged liposomes. In comparison with the freshly prepared dimeric sample, the more aggregated forms showed significantly reduced myotoxic activity. However, the edema-inducing activity of MjTX-I was independent of molecular association. Phospholipase A(2) activity on egg yolk, as well as anticoagulant activity, were undetectable both in the native and in the more associated forms. His, Tyr, and Trp residues of the toxin were chemically modified by specific reagents. Although the myotoxic and lethal activities of the modified toxins were reduced by these treatments, neither its edema-inducing or liposome-disrupting activities were significantly altered. Rabbit antibodies to native MjTX-I cross-reacted with the chemically modified forms, and both the native and modified MjTX-I preparations were recognized by antibodies against the C-terminal region 115-129 of myotoxin II from B. asper, a highly Lys49 PLA(2)-homologue with high sequencial similarity.


The effects of obesity and obesity-related conditions on colorectal cancer prognosis.
Colorectal cancer is the second-leading cause of cancer death in the United States among men and women combined. Refinements in screening, staging, and treatment strategies have improved survival from this disease, with over 65% of patients diagnosed with colorectal cancer surviving over 5 years after diagnosis. In the prognosis of colorectal cancer, clinicopathological factors are important. However, modifiable prognostic factors are emerging as significant contributors to cancer outcomes, including obesity and obesity-related inflammation and metabolic conditions. This report reviews the literature on obesity and obesity-related inflammation and metabolic disturbances and colorectal cancer outcomes (recurrence, disease-free survival, and/or mortality). A PubMed search was conducted of all English-language papers published between August 2003 and 2009 and cited in MEDLINE. Primary research papers were reviewed for colorectal cancer outcomes related to obesity, inflammation, or metabolic conditions. An association between body size and colorectal cancer recurrence and possibly survival was found; however, reports have been inconsistent. These inconsistent findings may be due to the complex interaction between adiposity, physical inactivity, and dietary intake. Circulating prognostic markers such as C-reactive protein, insulin-like growth factor, and insulin, alone or in combination, have been associated with prognosis in observational studies and should be evaluated in randomized trials and considered for incorporation into surveillance. The literature suggests that obesity and obesity-related inflammation and metabolic conditions contribute to the prognosis of colorectal cancer; however, comprehensive large scale trials are needed. Interventions to reduce weight and control inflammation and metabolic conditions, such as diabetes, need to be evaluated and rapidly translated to behavior guidelines for patients.


The opioid receptor antagonist, naloxone, enhances ocular motor compensation in guinea pig following peripheral vestibular deafferentation.
The opioid receptor antagonist, naloxone, has been demonstrated to enhance recovery from spinal cord injury and fluid percussion brain injury. The present study investigated, for the first time, the effects of naloxone on behavioral recovery following unilateral peripheral vestibular deafferentation (unilateral labyrinthectomy, UL) in guinea pig. An ip injection of 5 mg/kg naloxone 30 min pre-UL and 5 h post-UL was found to significantly reduce the frequency of spontaneous nystagmus relative to the vehicle control group (P < 0.005). However, a lower dose (2.5 mg/kg) had no effect. At either dose, the effects on the postural symptoms, yaw head tilt and roll head tilt, were small by comparison and in most cases nonsignificant. These results suggest that naloxone can reduce the ocular motor effects of UL in a dose-dependent fashion.


COVID-19: Update on Its Ocular Involvements, and Complications From Its Treatments and Vaccinations.
The coronavirus disease 2019 (COVID-19) came under the attention of the international medical community when China first notified the World Health Organization of a pneumonia outbreak of then-unknown etiology in Wuhan in December 2019. Since then, COVID-19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has appalled the world by spreading at a pandemic speed. Although ophthalmologists do not directly engage in the clinical care of COVID-19 patients, the ophthalmology community has become aware of the close ties between its practice and the pandemic. Not only are ophthalmologists at heightened risk of SARS-CoV-2 exposure due to their physical proximity with patients in routine ophthalmic examinations, but SARS-CoV-2 possesses ocular tropism resulting in ocular complications beyond the respiratory tract after viral exposure. Furthermore, patients could potentially suffer from adverse ocular effects in the therapeutic process. This review summarized the latest literature to cover the ophthalmic manifestations, effects of treatments, and vaccinations on the eye to aid the frontline clinicians in providing effective ophthalmic care to COVID-19 patients as the pandemic continues to evolve.


Growth factor-induced expression of macrophage migration inhibitory factor in osteoblasts: relevance to the plasminogen activator system.
Macrophage migration inhibitory factor (MIF) is a cytokine that mediates inflammatory processes in a variety of tissues. In this study, we examined the expression of MIF mRNA in the mouse osteoblastic cell line MC3T3-E1, whose proliferation is promoted by various growth factors. In the subconfluent state, transforming growth factor-beta, basic fibroblast growth factor, insulin-like growth factor-II, and fetal calf serum markedly upregulated MIF mRNA expression. The upregulation of MIF mRNA was less extensive when the cells were stimulated by the same growth factors in the overconfluent state. We also investigated the expression of MIF mRNA through a whole cell cycle from G0 phase when the osteoblastic cells were synchronized by serum starvation. The MIF mRNA expression, which gradually increased from the G0 and reached its maximum at the S phase, was nonperiodic. Moreover, human recombinant MIF upregulated the expression of urokinase plasminogen activator inhibitor-1 (PAI-1) precursor mRNA in human osteoblastic Saos-2 cells. Plasminogen activator (PA) is known to play an important role in bone metabolism, for example, in activation of procollagenase or growth factors indirectly via the formation of plasmin, and in mitogenic activity for osteoblastic cells. Our results suggest that MIF modulates the proliferation of osteoblasts and, moreover, bone tissue remodeling through the PA and plasmin system.


Spontaneous and radiation-induced renal tumors in the Eker rat model of dominantly inherited cancer.
Hereditary renal carcinoma (RC) in the rat, originally reported by R. Eker in 1954, is an example of a Mendelian dominant predisposition to a specific cancer in an experimental animal. At the histologic level, RCs develop through multiple stages from early preneoplastic lesions (e.g., atypical tubules) to adenomas in virtually all heterozygotes by the age of 1 year. The homozygous mutant condition is lethal at approximately 10 days of fetal life. Ionizing radiation induces additional tumors in a linear dose-response relationship, suggesting that in heterozygotes two events (one inherited, one somatic) are necessary to produce tumors, and that the predisposing gene is a tumor suppressor gene. No genetic linkage has yet been found between the Eker mutation and rat DNA sequences homologous to those in human chromosome 3p, the presumed site of the putative tumor suppressor gene responsible for human RC. Nonrandom loss of rat chromosome 5 in RC-derived cell lines is sometimes associated with homozygous deletion of the interferon gene loci at rat chromosome bands 5q31-q33. Since this locus is not linked with the predisposing inherited gene in the Eker rat, it probably represents a second tumor suppressor gene involved in tumor progression.


Hyperactivation and proliferation of lymphocytes from the spleens of flaky skin (fsn) mutant mice.
Mice homozygous for the flaky skin (fsn) single gene mutation have a severe hyperproliferative disease resulting in a complex phenotype, which includes widespread inflammation and autoimmunity. This study sought to characterize lymphocyte function of flaky skin mutant mice. Flaky skin lymphocytes show enhanced proliferation with in vitro mitogen stimulated spleen cells, as well as enriched splenic B- and T-cells. The production of IL-4 by fsn/fsn T-lymphocytes is increased dramatically compared with normal controls. Flaky skin lymphocytes exhibited increased responsiveness to IL-2, IL-4 and IL-7 in the absence of pre-activation, enhanced IgE production in response to ovalbumin immunization, and constitutive STAT6 activation. These data indicate that the cytokines IL-2, IL-4 and IL-7 likely contribute to the lymphocyte activation in fsn/fsn mutant mice. This lymphocyte hyperactivation may result in the development of systemic autoimmunity in fsn/fsn mutant mice.


Antisperm protein targets in azoospermia men.
The number of couples that meet the definition of infertility at reproductive ages is increasing worldwide. One of the most known conditions of infertility in males is azoospermia, defined as complete absence of spermatozoa in the semen. Azoospermia manifests in two forms, namely obstructive and non-obstructive azoospermia. Although the presence of antisperm antibody (ASA) has been reported in 88% of the patients with obstructive azoospermia (OA), interestingly, there is no data regarding ASA targets in OA individuals. The present study aimed to identify sperm antibody targets in a group of OA men. The present study was carried out on 27 OA infertile men and 27 healthy fertile age-matched males as cases and controls, respectively. The sperm proteome was separated using two-dimensional gel electrophoresis technique, transferred onto the polyvinylidene fluoride membrane, and blotted with the sera of a group of OA men. Then, it was compared with the membranes blotted with the sera of a group of healthy fertile men. Matrix-assisted laser desorption/ionization time-of-flight/time-of-flight (MALDI TOF/TOF) mass spectrometry was used to identify the different blotted spots and finally the results of the mass analysis were confirmed using reverse transcriptase polymerase chain reaction method. The results indicated that OA patients might produce antibody against two sperm proteins, Tektin-2 and triose phosphate isomerase. Moreover, the expressions of the two targeted proteins were confirmed at RNA level. The findings of the present study revealed two functionally important sperm proteins as antibody targets in azoospermic men.


The establishment, composition and severity of infection of gastro-intestinal parasites and their impact on productivity of Tswana kids in southern Botswana.
The presence of gastro-intestinal parasites in Tswana kids (n = 7) aged 1-3 weeks was studied for a period of 6 months at the Botswana College of Agriculture. The aims of this study were to find the time when they first contracted internal parasite infections, as well as to determine the severity of the infections and also its relation to production indicators (body mass and packed cell volume) of the kids as they grew older. The results indicate that they contracted coccidial and roundworm infections at approximately one month of age or immediately thereafter. The most prevalent internal parasite was coccidia, which occurred throughout the study period followed by roundworms and the least was the tapeworm, Moniezia expansa. Generally, the infection levels of all internal parasites were lower than the critical mean log (faecal oocyst/egg count + 1) of 3.3 inferred to cause reduced production in small stock. The correlation coefficients were all positive; 0.4-0.9 for individual internal parasites and production indicators, indicating that these internal parasites did not have any adverse effects on production. It was concluded that there was no need to treat kids of this age group for internal parasites.


The neurobiology of blindsight.
Some patients can respond to visual stimuli presented within their clinically absolute visual field defects that have been caused by partial destruction of striate cortex. This puzzling phenomenon of looking, pointing, detecting and discriminating without seeing has been called blindsight, and has fascinated philosophers and neuroscientists alike as a spotlight on the nature of unconscious or covert awareness, and the means it provides of studying the visual information carried by pathways other than the major route through the striate cortex.


Serious Illness Conversations With Doctors: Patients Using Information Obtained From Sources Other Than Their Doctors.
The purpose of this study was to examine how people with serious illnesses communicate information they have acquired about their illness from the Internet and social or mass media to their doctors. Twenty-two in-depth interviews of patients with serious or life-threatening illnesses were conducted and analyzed. Street's ecological perspective of communication was used to understand the processes that influence when and how patients bring information that they obtained from external sources to their doctors. The reactions patients received from their doctors affected their future communication with them. Results indicate doctors who have a dominant communication style often discourage patients from bringing outside information to them, and in some cases this results in patients changing doctors. On the other hand, doctors who are more attentive make patients feel more comfortable about bringing outside information to them, and this leads to more meaningful and beneficial conversations.


Balloon Sinuplasty: balloon-catheter dilation of paranasal sinus ostia for chronic rhinosinusitis.
More than 100 million patients worldwide suffer from chronic rhinosinusitis, and a considerable amount of money has been spent on research and treatments by healthcare providers. In the northern hemisphere, damp, temperate climates, along with higher concentrations of pollen, are associated with a higher prevalence of chronic rhinosinusitis. Owing to its persistent nature, the disease can become a significant cause of morbidity. If untreated, it can reduce quality of life and productivity. When medical treatment is not effective, surgery may offer an excellent outcome. Although functional endoscopic surgery has proven to be effective, many cases could be managed medically. Recent research has suggested that optimal medical treatment is as effective as surgery in patients with chronic rhinosinusitis at the end of 1 year. Balloon Sinuplasty (Acclarent, Inc., CA, USA) is a new technique in the management of sinusitis and is a hotly debated topic. It is a delicate, minimally invasive tool, and early research demonstrates promising outcomes in terms of safety and effectiveness. This novel technique has been approved by the US FDA. Recently, NICE raised no concerns regarding its safety and efficacy but will continue to review this procedure.


The effect of short term treatment with probiotic VSL#3 on various clinical and biochemical parameters in patients with liver cirrhosis.
The evidence is mounting that alterations of innate immunity and gut microbiota contribute to chronic liver disease and its complications. Modulation of intestinal microbiota is an emerging therapeutic strategy in hepatology. Probiotics through modulation of intestinal milieu have the potential to affect the course of liver disease. The data concerning the influence of probiotics on various plasma molecules and compounds involved in the pathogenesis of hyperdynamic circulatory state in liver cirrhosis is still not confluent and require further evaluation. In our study twenty patients with compensated and decompensated liver cirrhosis and ten healthy controls received probiotic VSL#3 daily for 28 days. Plasma levels of interleukin 6 (IL-6), vascular endothelial growth factor (VEGF), plasminogen activator inhibitor (PAI), macrophage inflammatory protein 3/α (MIP-3 α/CCL20), monocyte chemotactic protein-1α (MCP-1/CCL2), human myeloperoxidase (MPO), nitric oxide (NO), prostaglandins, thromboxane (TXB2) and big-endothelin were measured at baseline, day 14 and 28 of probiotic administration. The incidence of hepatic encephalopathy was assessed with critical flicker frequency. Changes in clinical, biochemical and microbiological parameters were evaluated. The stage of liver cirrhosis correlated with an increase in plasma levels of pro-inflammatory cytokines (IL-6) and chemotactic chemokines involved in immune cell trafficking (MIP-3α/CCL20). Probiotic administration in patients with liver cirrhosis led to modulation of plasma levels of several molecules and compounds measured (MIP-3α/CCL20, NO, big-endothelin, TXB2 and MPO). The grade of encephalopathy during the course of probiotic supplementation remained unaffected in both groups of patients. VSL#3 treatment was well tolerated and safe in patients with liver disease. In patients with compensated and decompensated liver cirrhosis, VSL#3 manipulates selected plasma molecules and compounds involved in hyperdynamic circulatory dysfunction. Short term VSL#3 administration affects several clinical and biochemical parameters commonly altered in liver cirrhosis.


Autonomous replication of plasmids bearing monkey DNA origin-enriched sequences.
Twelve clones of origin-enriched sequences (ORS) isolated from early replicating monkey (CV-1) DNA were examined for transient episomal replication in transfected CV-1, COS-7, and HeLa cells. Plasmid DNA was isolated at time intervals after transfection and screened by the Dpn I resistance assay or by the bromodeoxyuridine substitution assay to differentiate between input and replicated DNA. We have identified four monkey ORS (ORS3, -8, -9, and -12) that can support plasmid replication in mammalian cells. This replication is carried out in a controlled and semiconservative manner characteristic of mammalian replicons. ORS replication was most efficient in HeLa cells. Electron microscopy showed ORS8 and ORS12 plasmids of the correct size with replication bubbles. Using a unique restriction site in ORS12, we have mapped the replication bubble within the monkey DNA sequence.


Disruptive effects of prefeeding and haloperidol administration on multiple measures of food-maintained behavior in rats.
Four rats responded under a choice reaction-time procedure. At the beginning of each trial, the rats were required to hold down a center lever for a variable duration, release it following a high- or low-pitched tone, and press either a left or right lever, conditionally on the tone. Correct choices were reinforced with a probability of .95 or .05 under blinking or static houselights, respectively. After performance stabilized, disruptive effects of free access to food pellets prior to sessions (prefeeding) and intraperitoneal injection of haloperidol were examined on multiple behavioral measures (i.e., the number of trials completed, percent of correct responses, and reaction time). Resistance to prefeeding depended on the probability of food delivery for the number of trials completed and reaction time. Resistance to haloperidol, on the other hand, was not systematically affected by the probability of food delivery for all dependent measures.


Occupational stress and work-related upper extremity disorders: concepts and models.
While research has suggested that interventions targeted at occupational stress (job stress) factors may improve clinical and work outcomes related to work-related musculoskeletal disorders, the emerging hypotheses relating occupational stress to work-related upper extremity disorders (WRUEDs) are not particularly well known among occupational health providers and researchers. Generic job stress and health models and multivariable models of WRUEDs were described and evaluated. Models on occupational stress and health/WRUEDs offer unique perspectives on the role of occupational stressors on WRUEDs. However, the limited support for the structure and proposed mechanisms of these models suggest that investigations examining and validating proposed biobehavioral pathways are still needed. Difficulties in conceptualizing occupational stress have, in the past, hindered its systematic incorporation into occupational health research and prevention/intervention strategies. The present paper provides a common basis for researchers and practitioners with diverse backgrounds to understand job stress and its relation to WRUEDs in order to enhance future efforts. Given the present limitations in the field and the need for comprehensive approaches to WRUEDs, there is great potential for occupational health researchers and clinicians to advance knowledge in this area.


Concentrations of sucrose and nitrogenous compounds in the apoplast of developing soybean seed coats and embryos.
The apoplast of developing soybean (Glycine max cv Hodgson) embryos and seed coats was analyzed for sucrose, amino acids, ureides, nitrate, and ammonia. The apoplast concentration of amino acids and nitrate peaked during the most rapid stage of seed filling and declined sharply as the seed attained its maximum dry weight. Amino acids and nitrate accounted for 80 to 95% of the total nitrogen, with allantoin and allantoic acid either absent or present in only very small amounts. Aspartate, asparagine, glutamate, glutamine, serine, alanine, and gamma-aminobutyric acid were the major amino acids, accounting for over 70% of the total amino acids present. There was a nearly quantitative conversion of glutamine to glutamate between the seed coat and embryo, most likely resulting from the activity of glutamate synthase found to be present in the seed coat tissue. This processing of glutamine suggests a partly symplastic route for solutes moving from the site of phloem unloading in the seed coat to the embryo.


[Analysis of the prophylactic effect of nucleosides against reactivation of HBV in HBsAg-positive patients with non-hepatic tumors after chemotherapy].
To investigate the efficacy of nucleosides as a prophylactic agent against reactivation of hepatitis B virus (HBV) in HBsAg-positive patients with non-hepatic tumors after chemotherapy. Fifty-eight patients with non-hepatic tumors were divided into prevention group and control group. The patients of prevention group received nucleosides as a prophylactic agent before chemotherapy and were compared with the control ones about the clinical manifestation of HBV reactivation. Then, the patients of the control group were divided into three groups according to antiviral drugs, use or not and time of the use. The patients having HBV reactivation but never received nucleosides were included in the group A, the patients receiving nucleosides after having HBV reactivation were divided into the group B, and the patients receiving nucleosides before HBV reactivation were divided into the group C. The progression, prognosis and curative effect among the three groups were compared. The rate of HBV reactivation, incidence of severe hepatitis, mortality rate of the control group (61.1%, 27.8%, 16.7%) were significantly higher than those of the prevention group (13.6%, 0, 0), and liver dysfunction was more serious than that in the prevention group. In the control group, all the 5 patients of group A died of liver failure. Of the 13 patients in the group B, 4 cases suffered from severe hepatitis and 1 of them died of the disease. Of the 18 patients in the group C, 4 cases suffered from HBV reactivation, but the clinical manifestation was milder than that of the group B. Nucleosides can be used as a prophylactic measure to prevent HBV reactivation. If chemotherapy had begun, the use of nucleosides may reduce the risk of HBV reactivation. Even if patients had suffered from HBV reactivation, the use of nucleosides may still help the recovery of liver function and improve prognosis.


The Cdc42 GTPase-associated proteins Gic1 and Gic2 are required for polarized cell growth in Saccharomyces cerevisiae.
BEM2 of Saccharomyces cerevisiae encodes a Rho-type GTPase-activating protein that is required for proper bud site selection at 26 degrees C and for bud emergence at elevated temperatures. We show here that the temperature-sensitive growth phenotype of bem2 mutant cells can be suppressed by increased dosage of the GIC1 gene. The Gic1 protein, together with its structural homolog Gic2, are required for cell size and shape control, bud site selection, bud emergence, actin cytoskeletal organization, mitotic spindle orientation/positioning, and mating projection formation in response to mating pheromone. Each protein contains a CRIB (Cdc42/Rac-interactive binding) motif and each interacts in the two-hybrid assay with the GTP-bound form of the Rho-type Cdc42 GTPase, a key regulator of polarized growth in yeast. The CRIB motif of Gic1 and the effector domain of Cdc42 are required for this association. Genetic experiments indicate that Gic1 and Gic2 play positive roles in the Cdc42 signal transduction pathway, probably as effectors of Cdc42. Subcellular localization studies with a functional green fluorescent protein-Gic1 fusion protein indicate that this protein is concentrated at the incipient bud site of unbudded cells, at the bud tip and mother-bud neck of budded cells, and at cortical sites on large-budded cells that may delimit future bud sites in the two progeny cells. The ability of Gic1 to associate with Cdc42 is important for its function but is apparently not essential for its subcellular localization.


Thoughts on the criteria to determine the origin of volcanic unrest as magmatic or non-magmatic.
As our ability to detect volcanic unrest improves, we are increasingly confronted with the question of whether the unrest has a magmatic origin (magma on the move) or a non-magmatic origin from a change in the hydrothermal system (fluids that are not magma on the move) or tectonic processes. The cause of unrest has critical implications for the potential eruptive hazard (e.g. used in constructing Bayesian Event Trees), but is frequently the subject of debate, even at well-studied systems. Here, we propose a set of multi-disciplinary observations and numerical models that could be used to evaluate conceptual models about the cause of unrest. These include measurements of gas fluxes and compositions and the isotopic signature of some components (e.g. H2, He, C, SO2, H2 O, CH4 and CO2), the spatial and temporal characteristics of ground deformation, thermal output, seismicity, changes in gravity, and whether there is topographic uplift or subsidence spanning hundreds to thousands of years. In several volcanic systems, both magmatic and non-magmatic unrest is occurring at the same time. While none of these observations or models is diagnostic on its own, we illustrate several examples where they have been used together to make a plausible conceptual model of one or more episodes of unrest and whether eruptions did or did not follow the unrest. This article is part of the Theo Murphy meeting issue 'Magma reservoir architecture and dynamics'.


System for dispensing and continuously measuring the flow of solid particles into a hot high pressure gas flow.
A system for dispensing and continuously measuring the flow of solid particles into a hot high-pressure gas flow for times up to 1 h is described. A differential pressure across an orifice is used to force the particle flow. A strain gauge load cell is used to continuously sense the weight of the container from which the particles are being dispensed. Calibration results are included for flows of 100-microm-diam glass spheres through several orifices at rates from 1 to 15 g/s.


Virtual profiling: a new way to analyse phenotypes.
Simulation models can be used to perform virtual profiling in order to analyse eco-physiological processes controlling plant phenotype. To illustrate this, an eco-physiological model has been used to compare and contrast the status of a virtual fruit system under two situations of carbon supply. The model simulates fruit growth, accumulation of sugar, citric acid and water, transpiration, respiration and ethylene emission, and was successfully tested on peach (Prunus persica L. Batsch) for two leaf-to-fruit ratios (6 and 18 leaves per fruit). The development stage and the variation in leaf number had large effects of the fruit model variables dealing with growth, metabolism and fruit quality. A sensitivity analysis showed that changing a single parameter value, which could correspond to a genotypic change induced by a mutation, either strongly affects most of the processes, or affects a specific process or none. Correlation analysis showed that, in a complex system such as fruit, the intensity of many physiological processes and quality traits co-varies. It also showed unexpected co-variations resulting from emergent properties of the system. This virtual profiling approach opens a new route to explore the impact of mutations, or naturally occurring genetic variations, under differing environmental conditions.


Dual-Location Dual-Acid/Glutathione-Degradable Cationic Micelleplexes through Hydrophobic Modification for Enhanced Gene Silencing.
Gene therapy holds great promise for the treatment of acquired genetic disorders such as cancer with reduced side effects compared to chemotherapy. For gene therapy to be successful, it is crucial to develop efficient and nontoxic gene carriers to overcome the poor in vivo stability and low cellular uptake of nucleic acid-based therapeutic agents. Here, we report a new and versatile approach exploring a combination of hydrophobic modifications and dual-stimuli-responsive degradation (SRD) for controlled gene delivery with amphiphilic block copolymer-based nanocarriers. The block copolymer, synthesized by atom transfer radical polymerization, is designed with an acid-labile acetal linkage at the block junction and a pendant disulfide group in the hydrophobic block. The incorporation of labile linkages enables both disulfide-core-cross-linking and dual-location dual-acid/reduction-responsive degradation (DL-DSRD). Furthermore, the disulfide linkages integrated as hydrophobic moieties facilitate the nucleic acids to condense into nanometer-sized micelleplexes through electrostatic interactions of pendant dimethylamino groups with the anionic phosphate groups of the nucleic acids. Our preliminary results demonstrate that the DL-DSRD approach through hydrophobic modification is a robust platform in the development of gene delivery systems with enhanced colloidal stability, reduced cytotoxicity, and improved gene transfection efficiency.


Functional analyses of Pseudomonas putida benzoate transporters expressed in the yeast Saccharomyces cerevisiae.
Pseudomonas putida benF, benK, benE1, and benE2 genes encode proteins belonging to benzoate transporter super family, but those functions have not yet been elucidated. In this study we analyzed the functions of these gene products using the yeast Saccharomyces cerevisiae. P. putida gene products expressed in yeast cells were localized to the yeast plasma membrane and were involved in taking up benzoate into the cells. According to the sensitivity of yeast cell-growth to benzoate, it is proposed that benK, benE1, and benE2 gene products function as transporters, that take up benzoate into the cells, whereas the benF gene product functions as an efflux pump of benzoate.


Examining the associations of racism, sexism, and stressful life events on psychological distress among African-American women.
African-American women may be susceptible to stressful events and adverse health outcomes as a result of their distinct social location at the intersection of gender and race. Here, racism and sexism are examined concurrently using survey data from 204 African-American women residing in a southeastern U.S. urban city. Associations among racism, sexism, and stressful events across social roles and contexts (i.e., social network loss, motherhood and childbirth, employment and finances, personal illness and injury, and victimization) are investigated. Then, the relationships among these stressors on psychological distress are compared, and a moderation model is explored. Findings suggest that racism and sexism are a significant source of stress in the lives of African-American women and are correlated with one another and with other stressful events. Implications for future research and clinical considerations are discussed.


[Evolution of the concept of mixed states in bipolar disorder].
Historical development of the concept of mixed states from the times of its creation by E. Kraepelin till the modern unified criteria of bipolar mixed states establishment, which passed through a number of the outlined stages, is reviewed in the article. Critical evaluations of the official classifications currently accepted demonstrate their restrictive character. Results obtained for the development of a new more specific set of diagnostic criteria for mixed states are presented. Though the Kraepelin's definition of mixed states is still relevant, the article notes the tendency to conceptualize mixed states broadly and dimensionally. Preliminary proposals for the new classification DSM-V diagnostic system are reviewed and supposed contentious clauses of the difficulties in the development of a future edition of DSM-5 as well as ICD-11 are mentioned.


Closure of right pulmonary artery to left atrium fistula by duct occluder device.
We report the successful transcatheter closure of the right pulmonary artery fistula to the left atrium in a 4-year-old boy, who had presented with cyanosis and easy fatigability, identified after two-dimensional echocardiogram with bubble contrast study, computed tomography (CT) angiography, and cardiac catheterization. The fistula was successfully closed by a transcatheter approach using an 18/16 duct occluder device. There was marked improvement clinically and no complication on 2-months follow-up.


Serotonin receptor expression in hippocampus and temporal cortex of temporal lobe epilepsy patients by postictal generalized electroencephalographic suppression duration.
Prolonged postictal generalized electroencephalographic suppression (PGES) is a potential biomarker for sudden unexpected death in epilepsy (SUDEP), which may be associated with dysfunctional autonomic responses and serotonin signaling. To better understand molecular mechanisms, PGES duration was correlated to 5HT1A and 5HT2A receptor protein expression and RNAseq from resected hippocampus and temporal cortex of temporal lobe epilepsy patients with seizures recorded in preoperative evaluation. Analyses included 36 cases (age = 14-64 years, age at epilepsy onset = 0-51 years, epilepsy duration = 2-53 years, PGES duration = 0-93 s), with 13 cases in all hippocampal analyses. 5HT1A and 5HT2A protein was evaluated by Western blot and histologically in hippocampus (n = 16) and temporal cortex (n = 9). We correlated PGES duration to our previous RNAseq dataset for serotonin receptor expression and signaling pathways, as well as weighted gene correlation network analysis (WGCNA) to identify correlated gene clusters. In hippocampus, 5HT2A protein by Western blot positively correlated with PGES duration (p = .0024, R2 = .52), but 5HT1A did not (p = .87, R2 = .0020). In temporal cortex, 5HT1A and 5HT2A had lower expression and did not correlate with PGES duration. Histologically, PGES duration did not correlate with 5HT1A or 5HT2A expression in hippocampal CA4, dentate gyrus, or temporal cortex. RNAseq identified two serotonin receptors with expression that correlated with PGES duration in an exploratory analysis: HTR3B negatively correlated (p = .043, R2 = .26) and HTR4 positively correlated (p = .049, R2 = .25). WGCNA identified four modules correlated with PGES duration, including positive correlation with synaptic transcripts (p = .040, Pearson correlation r = .52), particularly potassium channels (KCNA4, KCNC4, KCNH1, KCNIP4, KCNJ3, KCNJ6, KCNK1). No modules were associated with serotonin receptor signaling. Higher hippocampal 5HT2A receptor protein and potassium channel transcripts may reflect underlying mechanisms contributing to or resulting from prolonged PGES. Future studies with larger cohorts should assess functional analyses and additional brain regions to elucidate mechanisms underlying PGES and SUDEP risk.


Photochromism of bis(2-alkyl-1-benzofuran-3-yl)perfluorocyclopentene derivatives.
[reaction: see text] Photochromic diarylethene derivatives having benzofuran heteroaryl groups, bis(2-methyl-1-benzofuran-3-yl)perfluorocyclopentene and bis(2-butyl-1-benzofuran-3-yl)perfluorocyclopentene, were synthesized, and their photochromic performance was examined in hexane solution as well as in the single-crystalline phase. The compounds exhibited photochromic reactivity even in the single-crystalline phase.


[Persistence of the third branchial arch].
The third branquial arch anomalies represent less than 1% of this deformites. The clinical manifestation can be varied althouth the formation of cysts is the commonest one and may appear at any time in life. We report the clinical case of a 7 year old boy with an neck mass. This mass was diagnosed as a branquial cyst. The patologist found a "timic reminescences". We carry out a review of the literature for this pathology.


Expanding Public Health Policy Analysis for Transformative Change: The Importance of Power and Ideas Comment on "What Generates Attention to Health in Trade Policy-Making? Lessons From Success in Tobacco Control and Access to Medicines: A Qualitative Study of Australia and the (Comprehensive and Progressive) Trans-Pacific Partnership".
It is increasingly recognised within public health scholarship that policy change depends on the nature of the power relations surrounding and embedded within decision-making spaces. It is only through sustained shifts in power in all its forms (visible, hidden and invisible) that previously excluded perspectives have influence in policy decisions. Further, consideration of the underlying neoliberal paradigm is essential for understanding how existing power dynamics and relations have emerged and are sustained. In their analysis of political and governance factors, Townsend et al have provided critical insight into future potential strategies for increasing attention to health concerns in trade policy. In this commentary we explore how incorporating theories of power more rigorously into similar political analyses, as well as more explicit critical consideration of the neoliberal political paradigm, can assist in analysing if and how strategies can effectively challenge existing power relations in ways that are necessary for transformative policy change.


Quinoline alkaloids and anti-platelet aggregation constituents from the leaves of Melicope semecarpifolia.
Three new quinoline alkaloids, melisemine, confusadine, and melicarpinone, together with twelve known compounds have been isolated from the leaves of Melicope semecarpifolia. The structures of these three compounds were determined through spectral analyses. Confusadine was demonstrated to be an anti-platelet aggregation constituent.


So called "fibro-osseous lesions" of tumorous origin. Biology confronts terminology.
The terms "fibro-osteo-cemental lesions" or "ossifying" and "cementifying fibromas" are confusing and should be discarded and replaced by clear and distinct terminology based on clinically, radiologically and histopathologically observable and reproducible characteristics. Histogenetic features and biological potential rather than tumour tissue products alone should be regarded as the basis for nomenclature. A classification of "fibro-osseous lesions" and three tumorous entities which have been defined by the terms "periodontoma", "psammous desmo-osteoblastoma" and "trabecular desmo-osteoblastoma" are presented and illustrated. These proposed entities go some way to bridge the gap between clinical diagnosis on the one hand and morphological and descriptive diagnosis on the other.


Low nm23 protein expression in infiltrating ductal breast carcinomas correlates with reduced patient survival.
Protein levels corresponding to nm23 were determined in normal and neoplastic breast tissues by immunoperoxidase staining. Nm23 protein levels were highest in normal breast epithelium, and lower in intraductal carcinomas. Based on nm23 staining, 39 infiltrating ductal carcinomas were separated into two groups: tumors with homogeneously high nm23 protein content, and tumors with low staining in either a homogeneous or heterogeneous pattern. Patients with low nm23 staining tumors, determined by three pathologists independently, had reduced survival times (alpha = 0.034, alpha = 0.012, alpha = 0.052 by the log rank test). Nm23 expression approached significance as an independent predictor of survival in Cox's proportional hazards model. The data provide the first correlation of low nm23 protein expression and reduced breast carcinoma patient survival.


Reproducibility of ambulatory blood pressure measures in African-American adolescents.
The primary purpose of this study was to evaluate the reproducibility of ambulatory blood pressure (BP) measures in African-American (AA) adolescents. Forty-one AA adolescents (age 16.6 +/- 1.3 yrs, 16F) with high-normal BP were measured on 3 occasions at 2-month intervals. Systolic BP (SBP), diastolic BP (DBP), and heart rate (HR) measures were recorded using the Spacelabs ambulatory BP monitor 90207 (Redmond, Wash) in the natural environment over 24-hour periods. Mixed model repeated measures ANOVAs were used to analyze the underlying error variance-covariance (V-C structures as well as mean differences for the 3 visits. Daytime measures: there were no significant mean differences across visits for daytime SBP, DSP, and HR (all Ps > .57). The error V-C matrix was heterogeneous Toeplitz for daytime SBP. Correlations between visits 1 and 2, 1 and 3, and 2 and 3 for daytime SBP were rs = 0.71, 0.47, and 0.71, respectively. Compound symmetry (CS) was the preferred model for daytime DBP (r = 0.68) and HR (r = 0.75). Nighttime measures: there were no significant mean differences across visits for nighttime SBP, DBP, and HR (all Ps > .29). The error V-C matrix was unstructured for nighttime SBP. Correlations between visits 1 and 2, 1 and 3, and 2 and 3 for SBP were rs = 0.74, 0.33, and 0.33, respectively. CS was preferred for night-time DBP (r = 0.58) and HR (r = 0.74). Collectively, these findings demonstrate that 3 measurements of ambulatory-derived DBP and HR measures are stable across 4 months, but SBP was only stable across 2 months in African-American adolescents.


Patterns of plasma LH, FSH, oestradiol and corticosteroids from birth to the first oestrous cycle in Meishan gilts.
Hormonal changes associated with pubertal development in a breed of pig exhibiting early puberty were determined. In Expt 1, blood from prepubertal Meishan gilts was collected at about 1 (n = 5), 10 (n = 5), 20 (n = 4), 30 (n = 5), 50 (n = 5), 70 (n = 10), 80 (n = 10) and 90 (n = 7) days of age. In Expt 2, females were sampled between 99 and 116 days of age before (n = 16) or during (n = 9) the first oestrous cycle. Serial blood samples were collected through a jugular catheter at 20 min intervals. In Expt 2, age at puberty was determined by daily examination for oestrus and weekly evaluation of plasma progesterone and found to occur at 111 days of age. Hormone profiles determined at least 19 days before the first oestrus were grouped to constitute a prepubertal stage. In Expt 1, mean concentration of LH was high at 1 day of age, significantly lower at 10 days and showed nonsignificant variations until 90 days. Frequency of LH pulses increased between 10 and 50 days (0.42 versus 0.85 pulse h-1, P < 0.05), decreased between 50 and 70 days (0.49 pulse h-1, P < 0.05) and remained low thereafter. Amplitude of LH pulses was high between 1 and 30 days and declined progressively until 80 days. Mean concentration of FSH was high between 1 and 20 days and decreased progressively until 80 days (7.2 and 2.3 ng ml-1, respectively, at 20 and 80 days, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Identification of novel proteins and phosphorylation sites in a tonoplast enriched membrane fraction of Arabidopsis thaliana.
Plant vacuoles play essential roles in many physiological processes, particularly in mineral nutrition, turgor provision and cellular signalling. The vacuolar membrane, the tonoplast, contains many membrane transporters that are critical in the execution of these processes. However, although increasing knowledge is available about the identity of proteins involved in these processes very little is known about the regulation of tonoplast transporters. By studying the phosphoproteome of tonoplast-enriched membranes, we identified 66 phosphorylation sites on 58 membrane proteins. Amongst these, 31 sites were identified in 28 membrane transporters of various families including tonoplast anion transporters of the CLC family, potassium transporters of the KUP family, tonoplast sugar transporters and ABC transporters. In a number of cases, the detected sites were well conserved across isoforms of one family pointing to common mechanisms of regulation. In other cases, isoform-unique sites were present, suggesting regulatory mechanisms tailored to the function of individual proteins. These results provide the basis for future studies to elucidate the mechanistic regulation of tonoplast membrane transporters.


Malignancy: Myeloma - the Elusive Cure.
Myeloma accounts for 1% of all malignancies and is characterised by the malignant expansion of plasma cells. It is essentially incurable with a median survival of 6 months untreated. Typically disseminated at presentation, myeloma requires systemic therapy, in those patients with advanced or progressive disease. Of single agent therapies, oral mephalan remains the gold standard, either alone or in combination with steroids. 40% will respond with an increase in median survival from under 1 year to around 36 months. Combination chemotherapy produces an advantage in remission induction but no clear benefit for either survival or remission duration has been shown over standard melphalan and prednisolone. Significant melphalan dose escalation produces increased response rates and increased complete remission rates, however at the expense of increased toxicity. This has been ameliorated to an extent using stem cell support, however, although autografting may be superior to conventional chemotherapy it is not a curative treatment and modifications such as purging or tandem procedures remain to be fully evaluated. Allogeneic transplantation is only an option in a tiny minority of patients and has a high treatment-related mortality. Interferon alpha may improve the relapse free survival but has little effect on overall survival as the majority of patients will relapse. Experimental approaches, such as P-gp inhibition or thalidomide, are appropriate in this poor prognosis group. In many patients palliative care remains the only therapeutic option and close attention should be therefore paid to the prevention and treatment of renal failure, anaemia, infection, hypercalcaemia and bone disease.


Out-of-hospital cardiac arrest in Victoria: rural and urban outcomes.
To compare the survival rate from out-of-hospital cardiac arrest in rural and urban areas of Victoria, and to investigate the factors associated with these differences. Retrospective case series using data from the Victorian Ambulance Cardiac Arrest Registry. All out-of-hospital cardiac arrests occurring in Victoria that were attended by Rural Ambulance Victoria or the Metropolitan Ambulance Service. 1790 people who suffered a bystander-witnessed cardiac arrest between January 2002 and December 2003. Bystander cardiopulmonary resuscitation was more likely in rural (65.7%) than urban areas (48.4%) (P = 0.001). Urban patients with bystander-witnessed cardiac arrest were more likely to arrive at an emergency department with a cardiac output (odds ratio [OR], 2.92; 95% CI, 1.65-5.17; P < 0.001), and to be discharged from hospital alive than rural patients (urban, 125/1685 [7.4%]; rural, 2/105 [1.9%]; OR, 4.13; 95% CI, 1.09-34.91). Major factors associated with survival to hospital admission were distance of cardiac arrest from the closest ambulance branch (OR, 0.87; 95% CI, 0.82-0.92), endotracheal intubation (OR, 3.46; 95% CI, 2.49-4.80), and the presence of asystole (OR, 0.50; 95% CI, 0.38-0.67) or pulseless electrical activity (OR, 0.73; 95% CI, 0.56-0.95) on arrival of the first ambulance crew. Survival rates differ between urban and rural cardiac arrest patients. This is largely due to a difference in ambulance response time. As it is impractical to substantially decrease response times in rural areas, other strategies that may improve outcome after cardiac arrest require investigation.


Characterization and outcomes of reinterventions in Food and Drug Administration-approved versus trial endovascular aneurysm repair devices.
Published rates of reintervention after endovascular aneurysm repair (EVAR) range from 10% to 30%. We evaluated a single university center's experience with reinterventions in the context of Food and Drug Administration (FDA)-approved and trial devices. Retrospective data collection was performed for patients who underwent infrarenal EVAR and required reintervention from 2000 to 2016. Trial devices included those used in FDA feasibility and pivotal trials. Time-to-event analysis was performed using Cox regression. Predictors of mortality and explantation were evaluated using logistic regression; survival analysis was performed using Kaplan-Meier methods. From 2000 to 2016, there were 1835 EVARs performed, and 137 patients (116 men; mean age, 72.2 ± 10.0 years) underwent reintervention with a mean aneurysm size of 5.9 ± 1.2 cm. The median follow-up was 5 years with an overall survival of 70.1%. The overall reintervention rate was 7.5%. FDA-approved devices had a reintervention rate of 6.4%, whereas trial devices had a rate of 14.4% (P < .001). For all devices, the most common cause of reintervention was type II endoleak (52.5%), followed by type I endoleak (18.2%), type III endoleak (9.5%), limb kink (7.3%), iliac occlusive disease (5.8%), endotension (1.5%), and other. The overall mean time to first reintervention was 2.3 ± 2.5 years, and univariate Cox regression identified male gender (hazard ratio, 1.91; 95% confidence interval [CI], 1.17-3.10; P = .010) and age at the time of EVAR (hazard ratio, 1.03; 95% CI, 1.01-1.05; P = .006) as risk factors for time to first reintervention. Among patients requiring reintervention, the mean number of reinterventions for trial devices was significantly greater than that for FDA-approved devices (2.18 vs 1.65; P = .01). Trial devices requiring reintervention had a nearly threefold higher odds for the need for more than two reinterventions (odds ratio, 2.88; 95% CI, 1.12-7.37; P = .034). Trial device, cause of reintervention, and type of reintervention were not predictive of the need for explantation or mortality, but the number of reinterventions was significantly associated with the need for explantation (odds ratio, 1.86; 95% CI, 1.17-2.96; P = .012). EVAR device and the need for explantation did not have an impact on mortality. Despite the rigorous nature of patient enrollment in clinical trials and the development of newer iterations of investigational devices, patients undergoing EVAR with trial devices are more likely to undergo a greater number of reinterventions than with FDA-approved devices. Although mortality and the need for explantation were not significantly associated with trial devices, the finding of a greater number of reinterventions highlights the need to properly inform patients willing to partake in investigational device trials.


Very long chain acyl-CoA dehydrogenase deficiency: successful treatment of acute cardiomyopathy.
Very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is a severe defect of mitochondrial fatty acid oxidation characterized by hypertrophic cardiomyopathy, pericardial effusion, steatosis, and hypoglycemia, often resulting in death by 4-5 months of age. The onset of cardiomyopathy and pericardial effusion is insidious and sudden, necessitating early diagnosis and intervention to prevent death. A family affected with this defect is described in which dietary therapy with medium-chain triglycerides (MCT) was associated with rapid reversal of these severe clinical symptoms. Diagnosis by acylcarnitine analysis in the neonatal period can provide the opportunity for early clinical intervention. Prenatal diagnosis from amniocytes by enzymology or in vitro analysis of the fat oxidation pathway with deuterated fatty acid precursors has also been successful and permits intervention at birth. Of 10 affected children, 7 untreated cases died within the first several months while the remaining 3 cases survived when treated with medium-chain triglycerides as the major source of dietary fat.


Osteopenia-osteoporosis syndrome in patients with thalassemia: understanding of type of bone disease and response to treatment.
With increased life expectancy, thalassaemic bone disease including osteopenia osteoporosis syndrome (OOS) is a major cause of bone pain and fragility fractures especially of the lumbar spine, which may be found in 70-80% adult patients with beta-thalassaemia worldwide, accounting for significant bone morbidity. The causes of OOS in thalassaemia syndromes are multifactorial, and the exact treatment is far from ideal. We undertook a prospective study of 34 thalassaemic patients to evaluate the effect of pamidronate and hormone replacement therapy (if hypogonadal) on bone quantity by DXA scan quality by histomorphometry of bone biopsy and bone dynamics by biochemical markers of bone turnover.Our results show that all patients had osteopenia with abnormal bones on histomorphometry before commencement of treatment. Thalassaemia major patients had high turnover bone disease and all responded favourably to treatment whereas intermedia patients had low turnover bone disease and responded poorly to treatment. Our data also showed that ICTP and PICP is a discriminatory test but histomorphometry is the only test for characterisation of bone morphology.


An Open Source Classifier for Bed Mattress Signal in Infant Sleep Monitoring.
To develop a non-invasive and clinically practical method for a long-term monitoring of infant sleep cycling in the intensive care unit. Forty three infant polysomnography recordings were performed at 1-18 weeks of age, including a piezo element bed mattress sensor to record respiratory and gross-body movements. The hypnogram scored from polysomnography signals was used as the ground truth in training sleep classifiers based on 20,022 epochs of movement and/or electrocardiography signals. Three classifier designs were evaluated in the detection of deep sleep (N3 state): support vector machine (SVM), Long Short-Term Memory neural network, and convolutional neural network (CNN). Deep sleep was accurately identified from other states with all classifier variants. The SVM classifier based on a combination of movement and electrocardiography features had the highest performance (AUC 97.6%). A SVM classifier based on only movement features had comparable accuracy (AUC 95.0%). The feature-independent CNN resulted in roughly comparable accuracy (AUC 93.3%). Automated non-invasive tracking of sleep state cycling is technically feasible using measurements from a piezo element situated under a bed mattress. An open source infant deep sleep detector of this kind allows quantitative, continuous bedside assessment of infant's sleep cycling.


The role of adipose-derived inflammatory cytokines in type 1 diabetes.
Adipose tissue dysfunction correlates with the development of diabetes. Mice with an adipocyte-specific deletion of the SUMO-specific protease SENP1 develop symptoms of type-1 diabetes mellitus (T1DM). Peri-pancreatic adipocytes (PATs) exert both systemic and paracrine effects on pancreases function. Our recent studies report that PATs of SENP1-deficient mice have increased proinflammatory cytokine production compared with other adipose depots. Proinflammatory cytokines produced from PATs not only have direct cytotoxic effects on pancreatic islets, but also increase CCL5 expression in adjacent pancreatic islets, which induces persistent inflammation in pancreases by acquisition of Th1 and Th17 effector T cell subsets. Small ubiquitin-like modifier (SUMO) can post-translationally conjugate to cellular proteins (SUMOylation) and modulate their biological functions. Several components in SUMOylation associate with T1DM susceptibility. We find that SUMOylation of NF-κB essential molecule NEMO augments NF-κB activity, NF-κB-dependent cytokine production and pancreatic inflammation. NF-κB inhibitor should provide therapeutic approach to block PAT inflammation and ameliorate the T1DM phenotype. We further propose that adipocytes in PATs may play a primary role in establishing pancreatic immune regulation at onset of diabetes, providing new insights into the molecular pathogenesis of type 1 diabetes.


The structural allograft composite in revision total knee arthroplasty.
Options in revision total knee arthroplasty with massive bone loss include arthrodesis, custom total knee arthroplasty, amputation, and revision with structural allograft-prosthesis composites. Advantages of structural allografts include their biologic potential, versatility, relative cost-effectiveness, bone stock restoration, and potential for ligamentous reattachment. Disadvantages include the risk of disease transmission and graft nonunion, malunion, collapse, or resorption. Extensive preoperative planning is required to rule out infection and to select properly the type and size of allograft and prosthetic implant. Implant designs with diaphyseal-engaging stems and increased prosthetic constraint often are required. The host site and allograft require meticulous preparation to maximize surface contact and mechanical interlock of the allograft and host. Allograft fixation must be rigid to allow for incorporation. Ligamentous reattachment to the allograft is most successful when done by a bone block technique. Common complications include instability and graft collapse.


Variations in glial cell line-derived neurotrophic factor release from biodegradable nerve conduits modify the rate of functional motor recovery after rat primary nerve repairs.
Accelerating axonal regeneration to shorten the delay of reinnervation and improve functional recovery after a peripheral nerve lesion is a clinical demand and an experimental challenge. We developed a resorbable nerve conduit (NC) for controlled release of glial cell line-derived neurotrophic factor (GDNF) with the aim of assessing motor functional recovery according to the release kinetics of this factor in a short gap model. Different types of resorbable NCs were manufactured from a collagen tube and multiple coating layers of poly(lactide-coglycolide), varying in poly(lactide-coglycolide) type and coating thickness to afford three distinct release kinetics of the neurotrophic factor. GDNF release was quantified in vitro. End-to-end suture and GDNF-free NC served as controls. Thirty-five Wistar rats underwent surgery. Motor recovery was followed from 1 to 12 weeks after surgery by video gait analysis. Morphometrical data were obtained at mid-tube level and distal to the NC. NCs were completely resorbed within 3 months with minimal inflammation. GDNF induced a threefold overgrowth of fibers at mid-tube level. However, the number of fibers was similar in the distal segment of all groups. The speed of recovery was inversely proportional to the number of fibers at the NC level but the level of recovery was similar for all groups at 3 months. The resorbable conduits proved their ability to modulate axonal regrowth through controlled release of GDNF. In relation to the dose delivered, GDNF strikingly multiplied the number of myelinated fibers within the NC but this increase was not positively correlated with the return of motor function in this model.


Effect of frequency and direction of horizontal oscillation on motion sickness.
Low frequency horizontal oscillation can cause motion sickness in some transportation systems, but the influence of the frequency, magnitude, direction, and duration of oscillation are poorly understood. It was hypothesized that motion sickness was independent of the direction of horizontal oscillation (fore-and-aft or lateral) and that there was no difference in the motion sickness produced by different frequencies of horizontal oscillation (between 0.2 and 0.8 Hz) when subjects were exposed to the same peak velocity of motion at each frequency. The 192 subjects were exposed within a closed cabin to sinusoidal oscillation with a velocity of +/- 0.50 ms(-1). Each subject experienced up to 30 min of motion while sitting with eyes open on a seat with a low backrest. The 16 conditions involved either fore-and-aft or lateral oscillation at 8 different frequencies: (i) 0.20 Hz, (ii) 0.25 Hz, (iii) 0.315 Hz, (iv) 0.40 Hz, (v) 0.50 Hz, (vi) 0.63 Hz, (vii) 0.80 Hz, or (viii) a stationary control condition. Subjects provided ratings of their motion sickness symptoms at 1-min intervals during the 30-min exposures. Each frequency of oscillation produced significantly more sickness than the static control conditions. Overall, there were no significant differences in the sickness produced by the seven different frequencies or between the sickness produced by fore-and-aft or lateral oscillation. Self-ratings of motion sickness susceptibility provided by subjects before participating in the experiment were positively correlated with their illness ratings during the experiment. With horizontal oscillation over the range 0.2 to 0.8 Hz, motion sickness is very approximately dependent on the peak velocity of oscillation. An acceleration frequency weighting having a gain inversely proportional to frequency would provide a convenient simple method of evaluating this type of motion in transport. However, the results suggest that a more complex weighting, reflecting decreased nauseogenicity at higher and lower frequencies would be more accurate. The direction of motion (i.e., fore-and-aft or lateral) had no effect on the sickness experienced.


Laparoscopic T-tube placement after common bile duct exploration: a simple technique.
Laparoscopic T-tube insertion into common bile duct (CBD) can be technically challenging. We describe a technique to facilitate CBD T-tube placement. The T-limb was cut to appropriate size and guttered along one-third of its circumference lengthwise. One end of T-limb was secured to the long stem using a tie. The free end was introduced into the abdomen through the epigastric port. Using nontraumatic graspers, this free end was advanced into the CBD. Once the whole of T-limb was inside, the tie was cut, and the T-tube would spring into place. Choledochotomy was sutured snugly around the T-tube. The long limb was taken out through the lateral port of the abdominal wall. There was no dislodgment or removal difficulty in all cases. This manoeuvre required <1 minute. This technique allows reliable and easier T-tube placement into CBD, requiring no ancillary devices. It shortens the steep learning curve. Laparoscopic placement of T-tube in CBD can be safely and easily manipulated in the described technique.


SURFRESIDE(2): an ultrahigh vacuum system for the investigation of surface reaction routes of interstellar interest.
A new ultrahigh vacuum experiment is described to study atom and radical addition reactions in interstellar ice analogues for astronomically relevant temperatures. The new setup - SURFace REaction SImulation DEvice (SURFRESIDE(2)) - allows a systematic investigation of solid state pathways resulting in the formation of molecules of astrophysical interest. The implementation of a double beam line makes it possible to expose deposited ice molecules to different atoms and/or radicals sequentially or at the same time. Special efforts are made to perform experiments under fully controlled laboratory conditions, including precise atom flux determinations, in order to characterize reaction channels quantitatively. In this way, we can compare and combine different surface reaction channels with the aim to unravel the solid state processes at play in space. Results are constrained in situ by means of a Fourier transform infrared spectrometer and a quadrupole mass spectrometer using reflection absorption infrared spectroscopy and temperature programmed desorption, respectively. The performance of the new setup is demonstrated on the example of carbon dioxide formation by comparing the efficiency through two different solid state channels (CO + OH → CO2 + H and CO + O → CO2) for which different addition products are needed. The potential of SURFRESIDE(2) to study complex molecule formation, including nitrogen containing (prebiotic) compounds, is discussed.


[Comparative studies on immunomodulation via hyperfractionated whole-body irradiation].
The effect of the humoral immune response on Sprague-Dawley rats by hyperfractionated total body irradiation was investigated. These experiments included single doses of total body irradiation (1 Gy, 2 Gy, 3 Gy) and the administration of 1 Gy and 2 Gy in two or three fractions 2 x 0.5 Gy, 3 x 0.33 Gy and 2 x 1.0 Gy, 3 x 0.66 Gy. The time between the fractions was six hours. The primary production of antibodies against erythrocytes of sheep were determined as immunity parameter. The immune stimulation could be achieved, when single doses of 1 or 2 Gy were delivered. The single dose of 3 Gy total body irradiation showed a small, not significant immunosuppression. A significant immunosuppression was observed in all our hyperfractionated experiments. The degree of immunosuppression was nearly equivalent in the hyperfractionated group (2 x 0.5, 3 x 0.33 Gy and 2 x 1.0, 3 x 0.66 Gy).


Zwolle Risk Score for Safety Assessment of Same-day Discharge after Primary Percutaneous Coronary Intervention.
The Zwolle risk score (ZRS) has been considered to be a useful tool for the systematic evaluation of patients for early discharge after primary percutaneous coronary intervention (PCI). Therefore, aim of this study was to evaluate the clinical utility of ZRS for the same-day discharge strategy after primary PCI at a tertiary care cardiac center of Karachi, Pakistan. This study was conducted at a tertiary care cardiac center between August 2019 and July 2020. Patients discharged within 24 h (same-day) of the primary PCI procedure were included. Patients were stratified as high- and low-risk based on ZRS score; low-risk (≤3) and high-risk (≥4). All patients were followed during 30-days post-procedure period for major adverse cardiac events (MACE). Out of 487 patients, 83.2% (405) were male and mean age was 54.6 ± 10.87 years. Mean ZRS was 2.34 ± 1.64 with 16.0% (78) patients in high-risk (≥4) group. 30-days MACE rate was observed to be 5.3% (26) with significantly higher rate among high-risk patients as compared to low-risk patients 12.8% (10) vs. 3.9% (16); p = 0.004 respectively with OR of 3.61 [1.57-8.29]. The area under the curve (AUC) of ZRS for prediction of 30-day MACE was 0.67 [95% CI: 0.58-0.77], ZRS ≥4 had sensitivity of 38.5% and specificity of 85.2% with AUC of 0.62 [95% CI: 0.50-0.74] for prediction of 30-day MACE. ZRS showed moderate discriminating potential in identifying patients with high-risk of MACE at 30-day after same-day discharge after primary PCI.


A Multi-Center Competing Risks Model and Its Absolute Risk Calculation Approach.
In the competing risks frame, the cause-specific hazard model (CSHM) can be used to test the effects of some covariates on one particular cause of failure. Sometimes, however, the observed covariates cannot explain the large proportion of variation in the time-to-event data coming from different areas such as in a multi-center clinical trial or a multi-center cohort study. In this study, a multi-center competing risks model (MCCRM) is proposed to deal with multi-center survival data, then this model is compared with the CSHM by simulation. A center parameter is set in the MCCRM to solve the spatial heterogeneity problem caused by the latent factors, hence eliminating the need to develop different models for each area. Additionally, the effects of the exposure factors in the MCCRM are kept consistent for each individual, regardless of the area they inhabit. Therefore, the coefficient of the MCCRM model can be easily explained using the scenario of each model for each area. Moreover, the calculating approach of the absolute risk is given. Based on a simulation study, we show that the estimate of coefficients of the MCCRM is unbiased and precise, and the area under the curve (AUC) is larger than that of the CSHM when the heterogeneity cannot be ignored. Furthermore, the disparity of the AUC increases progressively as the standard deviation of the center parameter (SDCP) rises. In order to test the calibration, the expected number (E) of strokes is calculated and then compared with the corresponding observed number (O). The result is promising, so the SDCP can be used to select the most appropriate model. When the SDCP is less than 0.1, the performance of the MCCRM and CSHM is analogous, but when the SDCP is equal to or greater than 0.1, the performance of the MCCRM is significantly superior to the CSHM. This suggests that the MCCRM should be selected as the appropriate model.


Correlation between gastric volume and organs at risk dose in adjuvant radiotherapy for left breast cancer.
The role of the gastric volume on the dose-effect relationship for these organs has not been investigated. The aim of the study was to evaluate the correlation between gastric volume and dose-volume histogram (DVH) parameters of the heart, left lung and stomach during left breast cancer radiotherapy (RT). Ninety-nine left breast cancer patients who got adjuvant radiotherapy were included. Study was classified into two groups based on treatment field arrangements: 1) breast tangential fields only (T) and 2) breast tangential and supraclavicular fields (TS). Organs DVHs were extracted. Descriptive statistics, Pearson correlation, linear regression analyses, and receiver operating characteristic (ROC) analyses were performed. There is a direct but not significant correlation between the gastric volume and doses to the stomach and left lung. For a 100-cc increase in the gastric volume, the stomach maximum dose and the V50 increased by 3 Gy and 4%, respectively. For the left lung, V4 and V5 increased by 1% for TS cases. Considering ROC analysis results, one can make a decision for about 74% of patients due to their left lung DVH parameters, using gastric volume as a known input data. The correlation between gastric volume and heart dose was not significant. The gastric volume of about 170 cc or less can result in lower dose to the stomach and ipsilateral lung during left breast cancer radiotherapy, especially for TS cases. To reach this gastric volume threshold, patients should be fast for 2 hours before the procedure of CT simulation and treatment.