Measuring levels of upper-extremity disability in employed adults using the DASH Questionnaire.
The Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire is a standardized outcome measure that captures upper-extremity disability from the perspective of the patient and is used to study clinical outcomes in musculoskeletal disorders. To constitute a frame of reference for clinical values it is important for clinicians to be able to compare clinical DASH scores with those of nonclinical populations. We collected DASH data from a working population in Germany that was outside clinical considerations and used the data to identify disability levels among identified subgroups as a basis for future clinical comparisons. We evaluated the DASH data using a convenience sample of 716 employed adults. Separate analyses were performed for each of the DASH scores, which were grouped according to age, gender, and type of vocational activity. The rank analysis of variance showed that statistically significant differences were found in Germany, differentiating between gender, age, and self-estimated vocational groups. Tests for interaction analyses of variance showed that increased disability was expressed as significantly higher mean DASH scores among older workers, female workers, and manual workers. This study provides comparative data for our clinical population and allows insight into current disability levels in a nonclinical population.


Scanning electron microscopical study on the fluorosis of enamel in rats.
Sixteen 28-day-old male rats of Wistar strain, with a mean body weight of 179 g, were divided into two equal groups. Each group of eight animals was maintained for 70 days on drinking water, ad lib., containing no fluorine (control group) and 100 ppm of fluorine (experimental group). All specimens examined were obtained from the incisal portions of the incisors. The following types of enamel specimens were prepared for scanning electron microscopy: (1) acid-etched specimens; (2) acid-etched specimens followed by low temperature microincineration; and (3) fractured specimens. The enamel formed during high fluoride exposure showed marked hypocalcification, that is, the crystallite density in the prism core and interprismatic region was lower than that of control animals. The organic substances appeared to increase in these regions. The changes were prominent in the outer and middle enamel layers. Such changes following fluoride administration appear to indicate an inhibition of enamel maturation, that is, an inhibition of the mineral deposition and/or an inhibition of organic matrix withdrawal.


Role of salivary malondialdehyde in assessment of oxidative stress among diabetics.
To evaluate and compare the salivary content of malondialdehyde (MDA) in patients with type 2 diabetes and control subjects. We conducted a cross-sectional study among 30 freshly diagnosed subjects of diabetes mellitus and 30 volunteers with no diabetes mellitus. Serum and salivary MDS levels were evaluated among all the subjects. The mean serum MDA in group controls and diabetics was 0.95 ± 0.13 and 3.11 ± 0.42. The mean salivary MDA in group controls and diabetics was 0.26 ± 0.05 μmol/l and 0.81 ± 0.07 μmol/l. The mean serum and salivary MDA levels were significantly higher in group diabetics than control group (p < 0.001 and <0.001) respectively. There was significant positive strong correlation between serum and salivary MDA levels in both controls and diabetics groups (r = 0.857, p < 0.001 and r = 0.891, p < 0.001) respectively. MDA was detectable in saliva in both diabetic and control groups. There was a positive significant correlation between salivary and serum MDA in diabetic and control subjects. Hence, salivary MDA appears to be an indicator of serum MDA concentration.


The concept map of felt stigma in patient with epilepsy.
Felt stigma is quite common among patients with epilepsy, but can be difficult for patients to express under clinical situations. The objective of this network study is to show that felt stigma can be deconstructed into a network of different concepts and to construct a map of their interconnections. Two hundred and ten patients with epilepsy were enrolled in our study. Stigma were assessed by Kilifi stigma scale for epilepsy containing 15 items about perceived stigma in patients with epilepsy. Network analysis were used as statistical analysis. We calculated node strength. Participants' average age was 31.18 years; 46.2 % of these patients were women and 50.5 % of them received education in university. The findings indicated that six edges with strongest regularized partial correlations existed in the network. Two concepts with the highest strength were S10"Inferior" and S14"Discriminate", while the concepts with the lowest strength were S3 "Embarrassed" and S13 "Mistreated". This network study offers an overview of the richness and complexity of associations involved in the structure of felt stigma in individuals with epilepsy. "Inferior" and "Discriminate" were the most central concepts of felt stigma in patients with epilepsy and the whole system of felt stigma tend to be a self-determined system. This map of concepts and their interrelations revealed in the map may offer some help for the guidance of clinicians and policy makers to reduce felt stigma in patients with epilepsy. However, as this study is based on cross-sectional data and using exploratory statistical tools like network analysis, all the conclusion above needed further confirmatory studies to validate them.


Pathogenic mechanisms of intestinal pneumatosis and portal venous gas: should patients with these conditions be operated immediately?
We aimed to histologically observe portal venous gas (PVG)-causing intestinal pneumatosis (IP) and evaluate pathogenic mechanisms and therapeutic strategies, including decisions on whether emergency surgery should be performed. Autopsy was performed in two cases of nonocclusive mesenteric ischemia (NOMI). We directly histologically observed the pathogenic mechanisms of IP caused by gas-producing bacteria and IP considered to be caused by mechanical damage to the intestinal mucosa. IP can be classified hypothetically into the following types according to pathogenesis: (1) infection, (2) rupture (damage) of the intestinal mucosa + increased intestinal intraluminal pressure, and (3) mixed type. In cases of IP caused by gas-producing bacteria or IP associated with intestinal wall damage extending beyond the mucosa to the deep muscular layer, emergency surgery should be considered. However, it is highly possible that patients who test negative for infection with gas-producing bacteria whose intestinal wall damage remains only in the mucosa can be conservatively treated.


The Role of 5-HT3 Receptors in Signaling from Taste Buds to Nerves.
Activation of taste buds triggers the release of several neurotransmitters, including ATP and serotonin (5-hydroxytryptamine; 5-HT). Type III taste cells release 5-HT directly in response to acidic (sour) stimuli and indirectly in response to bitter and sweet tasting stimuli. Although ATP is necessary for activation of nerve fibers for all taste stimuli, the role of 5-HT is unclear. We investigated whether gustatory afferents express functional 5-HT3 receptors and, if so, whether these receptors play a role in transmission of taste information from taste buds to nerves. In mice expressing GFP under the control of the 5-HT(3A) promoter, a subset of cells in the geniculate ganglion and nerve fibers in taste buds are GFP-positive. RT-PCR and in situ hybridization confirmed the presence of 5-HT(3A) mRNA in the geniculate ganglion. Functional studies show that only those geniculate ganglion cells expressing 5-HT3A-driven GFP respond to 10 μM 5-HT and this response is blocked by 1 μM ondansetron, a 5-HT3 antagonist, and mimicked by application of 10 μM m-chlorophenylbiguanide, a 5-HT3 agonist. Pharmacological blockade of 5-HT3 receptors in vivo or genetic deletion of the 5-HT3 receptors reduces taste nerve responses to acids and other taste stimuli compared with controls, but only when urethane was used as the anesthetic. We find that anesthetic levels of pentobarbital reduce taste nerve responses apparently by blocking the 5-HT3 receptors. Our results suggest that 5-HT released from type III cells activates gustatory nerve fibers via 5-HT3 receptors, accounting for a significant proportion of the neural taste response.


Comparison of the certified Copan eSwab system with commercially available cotton swabs for the detection of multidrug-resistant bacteria in rectal swabs.
Rectal swabs are well-implemented screening tools for multidrug-resistant bacteria (MDRB). Since certified swabs such as the Copan eSwab system experienced a delivery bottleneck during the COVID-19 pandemic, commercially available alternatives such as commonly used double-tipped cotton swabs had to be investigated, especially considering their similarity to professional cotton swabs for microbiological purposes. Diagnostic properties of commercial cotton swabs (comparable to Q-tips) and Copan eSwabs were qualitatively compared in a prospective single-center study using microbiological standard cultures and PCR methods for the detection of multidrug-resistant Gram-negative bacteria and vancomycin-resistant enterococci (VRE). A total of 196 swab pairs were collected from 164 participants. MDRB were detected in 36 of 164 cases (22%). There were neither false-negative nor false-positive results using commercial cotton swabs. In 8 of 196 samples (4.1%) MDRB species were detected only by using cotton swabs, including vancomycin-resistant Enterococcus faecium, OXA-48 producing Escherichia coli, ESBL-producing Klebsiella pneumoniae and ESBL-producing Escherichia coli. Commercial cotton swabs turned out to be a reliable alternative to Copan eSwabs. For practical use as a screening tool, relevant storage- and manufacturer-related contamination must be ruled out beforehand. Commonly available double-tipped cotton swabs can be used for rectal MDRB screening in the event of supply shortages of certified swabs. Further studies should clarify their suitability as a sampling system for nasopharyngeal MRSA carriage or even for the molecular biological detection of SARS-CoV-2.


MRI of perianal fistulae: a pictorial kaleidoscope.
Perianal fistulae are an abnormal communication between the anorectum and the perianal skin. A seemingly benign condition, it can be a cause of considerable distress to the patient if it is not mapped out adequately before embarking upon surgical correction. The persistence of residual disease complicates and up-stages the grade of the remnant fistula with increased risk of anal incontinence following surgery secondary to damage to the anal sphincter complex. Magnetic resonance imaging (MRI) can play a critical role in mapping the fistulae tract in relation to the anal sphincter complex and hence, act as a reliable guide for the surgeon to chart the optimised management of perianal fistulae. This review illustrates the role of MRI in the imaging evaluation of perianal fistulae, to facilitate a well-planned surgical course.


Kidney transplantation from hepatitis C virus-positive donors into hepatitis C virus-positive recipients: a safe way to expand the donor pool?
Because the disparity between the number of patients waiting for kidney transplants and the number of available cadaveric renal allografts continues to increase, there is a clear need to review the inclusion criteria for cadaveric donors. From January 2001 to March 2004, 24 patients with end-stage renal disease and hepatitis C virus (HCV) seropositivity underwent a kidney transplantation. In 10 transplants in HCV-positive recipients, the donor was HCV-positive (D+/R+) and in 14 cases the donor (1 living donor) was HCV-negative (D-/R+). Two of 3 HCV-RNA-negative recipients who received a HCV-RNA+ kidney became HCV-RNA+ in the posttransplantation period. There was a low rate of acute rejection (8.3%). One D+/R+ patient experienced an acute vascular rejection, which finally resulted in graft loss, due to the resurgence of severe infectious disease. The serum creatinine levels at 6 months posttransplantation were similar in both groups. Acute liver dysfunction was observed in 1 patient. There was no death in the entire series. Graft survival was 92% and 90% for D+/R+ and D-/R+, respectively.


Prenatal exposure to methadone HCL in relationship to body and brain growth in the rat.
Offspring from methadone-treated Wistar rats (last trimester of pregnancy), as compared to ad lib and pair fed controls, showed a reduction of body growth which continued throughout the 28-day period during which animals were observed after birth. Brain growth, as indicated by weight, cortical thickness and number of cells in the neocortex also showed a reduction in growth, which was apparent only during the first 14 days, after which there were no differences between the groups. However, in the hippocampus, neuronal density changes/unit area continued throughout the 28-day period in the methadone exposed group and to a lesser extent in the PF group suggesting that this area of brain did not return to normal dimensions or degree of maturation by the end of the third week. Since it has been suggested that any deficit in growth associated with prenatalmethadone-exposure might be due to a reduction in food intake, a group pair-fed to the amount of food consumed by the methadone group was included in the study. Generally, the data from the PF group was intermediate between that obtained from the ad lib fed controls and the methadone-exposed animals. Thus, while some of the growth reduction observed in the methadone-exposed pups could have been due to the impaired nutritional status of their mothers during the last third of pregnancy, a part of the reduced growth must be attributed to the drug treatment, since the reduced growth exceeded that observed in the pair-fed group.


The treatment of leukoderma after burns by a combination of dermabrasion and "chip" skin grafting.
The treatment of leukoderma after burns can be difficult. The white patches are often extensive and the adjacent scar tissue itself may need excision and this further increases the size of the final defect. Moreover, when sheet skin grafts are used it is difficult to produce an inconspicuous border between skin graft and surrounding normal skin. We have developed a new technique to treat depigmentation following burns with minimal donor site morbidity and encouraging results.


CHRD, a plant member of the evolutionarily conserved YjgF family, influences photosynthesis and chromoplastogenesis.
Studies on the carotenoid-overaccumulating structures in chromoplasts have led to the characterization of proteins termed plastid lipid-associated proteins (PAPs), involved in the sequestration of hydrophobic compounds. Here we characterize the PAP CHRD, which, based on sequence homology, belongs to a highly conserved group of proteins, YER057c/YjgF/UK114, involved in the regulation of basic and vital cellular processes in bacteria, yeast and animals. Two nuclear genes were characterized in tomato plants: one (LeChrDc) is constitutively expressed in various tissues and the other (LeChrDi) is induced by stress in leaves and is upregulated by developmental cues in floral tissues. Using RNAi and antisense approaches, we show their involvement in biologically significant processes such as photosynthesis. The quantum yield of photosynthetic electron flow in transgenic tomato leaves with suppressed LeChrDi/c expression was 30-50% of their control, non-transgenic counterparts and was ascribed to lower PSI activity. Transgenic flowers with suppressed LeChrDi/c also accumulated up to 30% less carotenoids per unit protein as compared to control plants, indicating an interrelationship between PAPs and floral-specific carotenoid accumulation in chromoplasts. We suggest that CHRD's role in the angiosperm reproductive unit may be a rather recent evolutionary development; its original function may have been to protect the plant under stress conditions by preserving plastid functionality.


Topography of initiation of N-glycosylation reactions.
Previous studies on the topography of the reactions leading to the formation of dolichol-P-P-Glc-NAc2Man9Glc3 have shown that these occur on both sides of the endoplasmic reticulum membrane (Hirschberg, C. B., and Snider, M. D. (1987) Annu. Rev. Biochem. 56, 63-87). Dolichol-P-P-GlcNAc2Man5 has been detected on the cytoplasmic side of the endoplasmic reticulum membrane while the subsequent dolichol-oligosaccharide intermediates face the lumen. Less clear is the side of the membrane where dolichol-P-P-GlcNAc2 is assembled. We now present evidence strongly suggesting that the active sites of the enzymes catalyzing the synthesis of this latter intermediate are on the cytoplasmic side of the endoplasmic reticulum membrane. In addition, dolichol-P-P-GlcNAc2 has also been detected on this side. Incubations of sealed, "right side out" rat liver endoplasmic reticulum-derived vesicles with [beta-32P] UDP-GlcNAc in the presence of 5-Br-UMP resulted in the formation of radiolabeled dolichol-P-P-GlcNAc and dolichol-P-P-GlcNAc2 under conditions where there was complete inhibition of transport of the nucleotide sugar. In other experiments with the above radiolabeled nucleotide sugar and sealed vesicles, it was demonstrated that EDTA (a membrane-impermeable reagent) inhibited the N-acetylglucosamine-1-phosphate transferase under conditions where transport of the nucleotide sugar into the lumen was unaffected. Finally, sealed vesicles were first incubated with [32P]UDP-GlcNAc and subsequently with UDP-Gal and soluble galactosyltransferase. This resulted in galactosylation of dolichol-P-P-GlcNAc2. The above results, together with the previous observations, strongly suggest that all reactions leading to this latter dolichol intermediate occur on the cytosolic side of the endoplasmic reticulum membrane.


The effects of convective cooling and rewarming on systemic and central nervous system physiology in isoflurane-anesthetized dogs.
Recent studies have demonstrated that small (i.e., 2-5 degrees C) reductions in temperature may protect the brain and spinal cord from ischemic injury. The present study evaluated the physiologic response of anesthetized animals to convective-based cooling and warming. Six shaved, isoflurane-anesthetized (1.50% end-expired; 1 MAC), pancuronium-paralyzed dogs were subjected to temperature manipulation. The flow of cool (13-14 degrees C) or warm (39-41 degrees C) air was uniformly applied to the the dorsal and lateral surfaces of the dog using an inflatable blanket with perforations in the interior surface. Convective cooling reduced pulmonary artery temperature (Tpa) from 37.0 +/- 0.2 degrees C (Mean +/- S.D.) to 33.0 +/- 0.0 degrees C over a 93 +/- 18 min period. Thereafter, the active cooling was discontinued and passive cooling resulted in a further reduction in Tpa to 32.4 +/- 0.3 degrees C over the next 60 min. Institution of convective warming resulted in an increase in Tpa from 32.4 +/- 0.3 to 33.0 +/- 0.0 degrees C in 23 +/- 14 min and from 33.0 to 37.0 +/- 0.0 in an additional 137 +/- 26 min. During the periods of active cooling, passive cooling and active warming, there were strong correlations between Tpa and temperature within the brain, cisterna magna, parietal epidural space, lumbar subarachnoid space and other commonly used temperature measurement sites non-invasively monitored (e.g. tympanic membrane, esophagus, rectum) r greater than or equal to 0.97; P less than 0.0001). The combination of isoflurane anesthesia (a potent EEG-suppressor) plus mild hypothermia (less than 34 degrees C) resulted in an EEG attenuation in five dogs, two of which progressed to burst suppression. The magnitude of EEG changes correlated with the degree of temperature reduction. Upon rewarming to 37 degrees C, all dogs had normal EEG activity and normal brain concentrations of high energy phosphates, glucose and lactate. Blood pressure and cardiac output did not change during the study and no dog exhibited acid-based anomalies or blood lactate accumulation. Whole body oxygen consumption and heart rate decreased in a temperature-dependent fashion. Cardiac rhythm disturbances were rare. The authors conclude that convection-based corporeal cooling and rewarming are efficacious methods for non-invasively and uniformly altering CNS temperatures without adversely affecting cerebral or systemic physiology.


Oxidative stress induced by HCH in Hydrilla verticillata (l.f.) Royle: modulation in uptake and toxicity due to Fe.
The effect of hexachlorocyclohexane (HCH) singly and in combination with iron was studied on chlorophyll, malondialdehyde, cysteine, total -SH contents and potassium ion leakage in the plants of Hydrilla verticillata. The effect of HCH was also studied on glutathione (reduced and oxidised) content and superoxide dismutase activity. The results showed an increase in malondialdehyde content and potassium ion leakage with increase in HCH concentrations, however, the presence of Fe played a protective role. The chlorophyll content was decreased with increase in HCH concentrations and exposure period. However, the chlorophyll content at 2 and 5 microg ml(-1) was significantly higher in HCH-treated plants as compared to HCH + Fe after 168 h, showing protective role of Fe. The results showed significant increase up to 1 microg ml(-1) in cysteine content with increase in concentrations in both the treatments. The total -SH content was increased with increase in concentrations in both the treatments. In HCH-treated plants, non-significant change was noticed in reduced glutathione (GSH) content however, oxidised glutathione (GSSG) content was increased significantly after 168 h, indicative of oxidative stress. In addition, superoxide dismutase activity was increased non-significantly with increase in HCH concentrations. The accumulation of HCH singly and in presence of Fe was concentration- and duration-dependent. The accumulation of HCH was decreased in presence of Fe at higher concentrations. In contrast, the accumulation of Fe was increased in presence of HCH at higher concentrations. The results showed that malondialdehyde content and potassium ions leakage are the primary responses of toxicity.


[Neuromeningeal cryptococcosis and AIDS: an 11-case series from Libreville, Gabon].
Neuromeningeal cryptococcosis occurs mainly in immunodepressed patients and especially AIDS patients. The purpose of this study was to determine the clinical and prognostic features of this severe brain infection. This retrospective study was carried out on HIV-infected patients hospitalized for cryptococcal meningitis in the internal medicine unit of a military hospital in Libreville, Gabon from January 1, 2006 to November 31, 2009. Eleven cases of cryptococcosis were identified among a total of 290 cases of AIDS. Mean patient age was 39 years. The main clinical manifestation was headache that was either isolated or associated with other cerebral signs. In all cases, cerebrospinal fluid analysis demonstrated a clear aseptic aspect with direct examination after addition of India ink showing the presence of encapsulated yeast cells identified as cryptococcus. The patient was treated with amphotericin B and fluconazole. The mortality rate was 81.8% (9/11 cases). Since the manifestations of cryptococcosis during clinical AIDS are non-specific, systematic screening is recommended in AIDS patients. Early treatment could reduce mortality.


Reorienting attention across the horizontal and vertical meridians: evidence in favor of a premotor theory of attention.
Stimuli presented in a non-attended location are responded to much slower than stimuli presented in an attended one. The hypotheses proposed to explain this effect make reference to covert movement of attention, hemifield inhibition, or attentional gradients. The experiment reported here was aimed at discriminating among these hypotheses. Subjects were cued to attend to one of four possible stimulus locations, which were arranged either horizontally or vertically, above, below, to the right or left of a fixation point. The instructions were to respond manually as fast as possible to the occurrence of a visual stimulus, regardless of whether it occurred in a cued or in a non-cued location. In 70% of the cued trials the stimulus was presented in the cued location and in 30% in one of the non-cued locations. In addition there were trials in which a non-directional cue instructed the subject to pay attention to all four locations. The results showed that the correct orienting of attention yielded a small but significant benefit; the incorrect orienting of attention yielded a large and significant cost; the cost tended to increase as a function of the distance between the attended location and the location that was actually stimulated; and an additional cost was incurred when the stimulated and attended locations were on opposite sides of the vertical or horizontal meridian. We concluded that neither the hypothesis postulating hemifield inhibition nor that postulating movement of attention with a constant time can explain the data. The hypothesis of an attention gradient and that of attention movements with a constant speed are tenable in principle, but they fail to account for the effect of crossing the horizontal and vertical meridians. A hypothesis is proposed that postulates a strict link between covert orienting of attention and programming explicit ocular movements. Attention is oriented to a given point when the oculomotor programme for moving the eyes to this point is ready to be executed. Attentional cost is the time required to erase one ocular program and prepare the next one.


Management of chronic lunotriquetral ligament tears.
Treatment of chronic disruptions of the lunotriquetral (LT) ligament is not well-defined. Eleven patients treated by LT fusion with use of a compression screw are reported. The injury frequently resulted from hyperextension of the wrist. Pain on the ulnar side of the wrist, limited motion, and tenderness over the LT joint exacerbated by ballottement were present. Standard radiographs were normal. Arthrography showed the ligamentous tear in all cases. After operation, immobilization was continued until fusion was apparent radiographically. Fusion was achieved in all cases between 2 and 5 months. Four patients were free of pain, four patients had pain only at the extremes of motion, and three patients had persistent pain. Mean wrist motion was as follows (preoperative/postoperative): flexion (53 degrees/45 degrees), extension (60 degrees/49 degrees), radial deviation (17 degrees/21 degrees), and ulnar deviation (25 degrees/18 degrees). Maximum grip strength as a percentage of the uninjured side was 73% preoperatively and 59% postoperatively. LT tears can exist de novo or as part of the ulnar impaction syndrome; a method for differentiation is presented.


Cortico-hippocampal Schemas Enable NMDAR-Independent Fear Conditioning in Rats.
The neurobiology of memory formation has been studied primarily in experimentally naive animals, but the majority of learning unfolds on a background of prior experience. Considerable evidence now indicates that the brain processes initial and subsequent learning differently. In rodents, a first instance of contextual fear conditioning requires NMDA receptor (NMDAR) activation in the dorsal hippocampus, but subsequent conditioning to another context does not. This shift may result from a change in molecular plasticity mechanisms or in the information required to learn the second task. To clarify how related events are encoded, it is critical to identify which aspect of a first task engages NMDAR-independent learning and the brain regions that maintain this state. Here, we show in rats that the requirement for NMDARs in hippocampus depends neither on prior exposure to context nor footshock alone but rather on the procedural similarity between two conditioning tasks. Importantly, NMDAR-independent learning requires the memory of the first task to remain hippocampus dependent. Furthermore, disrupting memory maintenance in the anterior cingulate cortex after the first task also reinstates NMDAR dependency. These results reveal cortico-hippocampal interactions supporting experience-dependent learning.


In-situ fabrication of ionic liquids/MIL-68(In)-NH2 photocatalyst for improving visible-light photocatalytic degradation of doxycycline hydrochloride.
Metal-organic framework (MOFs)-based composites have been popular in photocatalysis due to their outstanding physicochemical properties, such as large surface area, high activity and good transmission properties. Herein, a method of ionic liquids (ILs)-assisted synthesis of IL/MIL-68(In)-NH2 composite materials were proposed, and composites were used for visible light catalytic degradation of doxycycline hydrochloride (DOXH). The effects of four kinds of ionic liquids on the structure and photocatalytic properties of the composites were explored, including diethylenetriamine acetate ([DETA][OAc]), diethylenetriamine hexafluorophosphate ([DETA][PF6]), 1-ethyl-3-methylimidazole acetate ([EMIM][OAc]) and 1-ethyl-3-methylimidazole hexafluorophosphate ([EMIM][PF6]). The results show that the introduction of different ionic liquids affects the grain growth of MOFs material and photocatalytic activity. Among them, ILDAc/MIL-68(In)-NH2 samples showed the highest photocatalytic activity. 92% removal rate of doxycycline hydrochloride and kinetic degradation constant (0.00918 min-1) was observed under the optimal addition of ILDAc (10 wt%), which was 4.6 times that of MIL-68(In)-NH2. The enhancement was attributed to a combined effect of efficient adsorption at low concentration, an increase of active sites, and efficient charge transfer. In addition, the effects of pH and initial concentration were investigated. Finally, the photocatalytic mechanism of DOXH was elucidated, and the possible intermediate products and degradation pathways were discussed. Considering the excellent photostability and ultra-fast photodegradation of ILDAc/MIL-68(In)-NH2, this study opens up a new prospect for the preparation of ionic liquids functionalized MOFs with wide practical application value.


In vitro and in vivo evaluation of targeting tumor with folate-based amphiphilic multifunctional stabilizer for resveratrol nanosuspensions.
Resveratrol (RSV) nanosuspensions, with long term stability and targeting delivery ability, were designed and demonstrated by in vitro and in vivo model. The folate modified distearoylphosphatidyl ethanolamine-polyethylene glycol (DSPE-PEG-FA), as target delivery carrier, was synthesized and confirmed by FTIR and 1H NMR. D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and DSPE-PEG-FA used as stabilizers formed two RSV nanosuspensions (RSV-NA and RSV-NB), which were prepared by anti-solvent precipitation method and optimized by central composite design-response surface model (CCD-RSM). The morphology of RSV nanosuspensions showed flake shapes and spherical shapes by SEM. And the distribution of particles was uniform by TEM and AFM. The two RSV nanosuspensions displayed an amorphous state, by XRPD and DSC determination. At room temperature, the optimum RSV nanosuspensions showed long term stability for 20days. The cell proliferation and morphology study revealed that the RSV nanosuspensions significantly enhanced the in vitro cytotoxicity against A549 cells in a dose- and time-dependent manner. The recommended safe concentration was 5μM for in vitro study. In vivo studies of the two nanosuspensions also displayed higher antitumor efficacy by reduced tumor volume and weight. Compared with the saline group, the tumor inhibition ratio of the RSV-NA was 61.53±18.36% and RSV-NB was 64.61±21.13%. The mice weight of the RSV-NA group and RSV-NB group was also maintained constant increasing. These results demonstrated that TPGS and DSPE-PEG-FA could be used as stabilizers for stable RSV nanosuspensions formulation with the potentiality for targeting delivery to human alveolar carcinoma cells with high stability and efficacy.


Contraception usage over the age of 40 in Polish female population aged 45 - 54.
Analysis of particular contraception method usage over the age of 40 as declared by Polish women aged 45-54 according to their education level and place of residence. The research was conducted with help of a standardized questionnaire in a Polish nationwide representative sample of women aged 45-54 years (n = 1083) in April 2004. 28% of sexually active women over 40 years old did not use any contraception methods. Most of them were country dwellers (41%), a lower proportion lived in small/moderate towns (27%), and a significantly lower percentage was made by big city dwellers (14%). Among the most popular contraception methods the respondents indicated coitus interruptus (32%), condoms (30%) and the calendar method (26%). Oral contraception was used by 12% of women. A considerable percentage of sexually active women aged more than 40 years do not use any contraception method at all or use unreliable methods. Highly reliable methods (condoms, contraception pills) are much more popular among city dwellers. Contraception pills are used by twice as many city dwellers as rural dwellers (16% versus 8%) and by 12% of women from small/moderate towns. Rates of condom usage are also differentiated and vary from 42% in big cities to 26-27% in rural areas and small/moderate towns. Although poor availability of the contraception pill might explain some differences in its usage, it is difficult to quote this factor in the case of condoms.


Concomitant degradation of beta-catenin and GSK-3 beta potently contributes to glutamate-induced neurotoxicity in rat hippocampal slice cultures.
Increasingly, published evidence links glutamate with the pathogenesis of Alzheimer's disease. We investigated the molecular mechanism underlying glutamate-induced neurotoxicity in hippocampus, which is primarily linked to cognitive dysfunction in Alzheimer's disease. Acute exposure of rat hippocampal slices to glutamate significantly induced cell death, as determined by media lactate dehydrogenase levels and PI staining. Moreover, this was accompanied by Ca2+ influx and calpain-1 activation, as confirmed by the proteolytic pattern of spectrin. Notably, glutamate-induced calpain-1 activation decreased the level of beta-catenin, and this process appeared to be independent of glycogen synthase kinase 3beta (GSK-3beta), since glutamate also led to loss of GSK-3beta. Calpeptin, a calpain inhibitor, attenuated the glutamate-mediated degradations of spectrin, synaptophysin, and beta-catenin except GSK-3beta and modestly increased cell survival. In contrast, the NMDA receptor antagonist 2-amino-5-phosphonopentanoic acid (APV) effectively reduced all glutamate-evoked responses, i.e., the breakdowns of spectrin, synaptophysin, beta-catenin and GSK-3beta, and cell death. Pharmacological studies and in vitro calpain-1 proteolysis confirmed that in the glutamate-treated hippocampus, calpain-1-mediated decrease of beta-catenin could occur independently of GSK-3beta and of proteasome, and that GSK-3beta degradation is independent of calpain-1. These findings together provide the first direct evidence that glutamate promotes the down-regulations of beta-catenin and GSK-3beta, which potently contribute to neurotoxicity in hippocampus during excitotoxic cell death, and a molecular basis for the protection afforded by calpeptin and APV from the neurotoxic effect of glutamate.


Diagnostic efficacy of serum anti-phospholipase A2 receptor antibodies for idiopathic membranous nephropathy in patients with diabetic kidney disease.
Serum anti-phospholipase A2 receptor (anti-PLA2R) antibodies are highly accurate in diagnosing idiopathic membranous nephropathy (IMN) in populations with kidney disease. However, the diagnostic value of anti-PLA2R antibodies for IMN in diabetic kidney disease (DKD) is unclear. The objective of this study is to determine the diagnostic efficacy and the optimal cut-off value of this marker in populations with DKD. This study included 227 patients with type 2 diabetes who were admitted to the Department of Nephrology of the Chinese People's Liberation Army General Hospital from May 2016 to January 2018 and underwent pathological diagnosis by renal biopsy. Anti-PLA2R antibodies were detected by enzyme-linked immunosorbent assay in this population. According to the pathological results, the participants were divided into an IMN group and non-membranous nephropathy (non-MN) group. The clinical characteristics were analyzed, the diagnostic ability of anti-PLA2R antibodies was evaluated, and the receiver operating characteristic (ROC) curve was constructed to obtain the optimal cut-off value. There were 45 patients in the IMN group, accounting for 19.8% of the study sample. The patients in this group were older at the time of renal biopsy than the non-MN group and presented a shorter duration of diabetes, better glycemic control, lower blood pressure and uric acid, and better renal function; in addition, their clinical symptoms indicated nephrotic syndrome. The optimal cut-off value for anti-PLA2R antibodies for the diagnosis of IMN in DKD was 2.71 Ru/ml, sensitivity was 0.800, specificity was 0.951, positive predictive value was 0.800, negative predictive value was 0.951, accuracy was 0.921, and the Yoden index was 0.750. The area under the ROC curve was 0.87 (95% CI, 0.788-0.952) (p < 0.001). Patients in the IMN group were older, had better renal function and general condition, and the clinical symptoms indicated nephrotic syndrome. Anti-PLA2R antibodies had a good diagnostic performance for IMN in the population with DKD, and the optimal cut-off value was 2.71.


Safety at waste and recycling industry: Detection and mitigation of waste fire accidents.
In this study, NASA's VIIRS (Visible Infrared Imaging Radiometer Suite) fire hotspots and data of the Swedish Civil Contingencies Agency (MSB), collected between 2012 and 2018, was integrated to characterize waste fire incidents that were detected by VIIRS and reported to MSB (DaR), detected by VIIRS but not reported to MSB (DbNR) and that are reported to MSB but not detected by VIIRS (RbND). Results show that the average number of open waste fire incidents per million capita per year (AFIPMC) in Sweden, for the period 2012-2018, ranges from 2.4 to 4.7. Although a weak correlation exists (r = 0.44, P = 0.1563, one tailed) between years and number of fire incidents (MSB + VIIRS fires), a continuous increase in number of fire incidents was recorded between 2014 and 2018. It is concluded that the use of satellite data of fire anomalies, in-combination with the use of incident reports, will help in formalizing more reliable and comprehensive waste fire statistics. Another focus area of the article is to consolidate the recommendations and routines for safe storage of waste and biofuels and to present the lessons that can be learnt from past fire incidents. The article also discusses the technical, political, economic, social, and practical aspects of waste fires and provide a baseline for future research and experimentation.


Effects and Mechanisms of Cage versus Floor Rearing System on Goose Growth Performance and Immune Status.
Currently, FRS and CRS are the two predominant dryland rearing systems in the goose industry. However, the effects of these two systems on goose growth performance and health, as well as the underlying mechanisms, have not been fully clarified. Thus, this study aimed to compare growth performance and immune status, as well as investigate the genome-wide transcriptomic profiles of spleen in geese, between CRS and FRS at 270 d of age. Phenotypically, the body weight and body size traits were higher in geese under FRS, while the weight and organ index of spleen were higher in geese under CRS (p < 0.05). Noticeably, the bursa of Fabricius of geese under FRS was degenerated, while that under CRS was retained. At the serum level, the immune globulin-G (IgG) and interleukin-6 (IL-6) levels were higher in geese under CRS (p < 0.05). At the transcriptomic level, we identified 251 differentially expressed genes (DEGs) in the spleen between CRS and FRS, which were mainly enriched in scavenger receptor activity, inflammatory response, immune response, neuroactive ligand-receptor interaction, phenylalanine metabolism, ECM receptor interaction, calcium signaling pathway, phenylalanine, tyrosine, and tryptophan biosynthesis, regulation of actin cytoskeleton, and MAPK signaling pathways. Furthermore, through protein-protein interaction (PPI) network analysis, ten candidate genes were identified, namely, VEGFA, FGF2, NGF, GPC1, NKX2-5, FGFR1, FGF1, MEIS1, CD36, and PAH. Further analysis demonstrated that geese in CRS could improve their immune ability through the "phenylalanine metabolism" pathway. Our results revealed that the FRS improved growth performance, whereas the CRS improved goose immune function by increasing levels of IL-6 and IgG in serum. Moreover, the phenylalanine metabolism pathway could exert positive effects on immune function of geese under CRS. These results can provide reliable references for understanding how floor and cage rearing systems affect goose growth performance and immune capacity.


Overgrowth syndromes with vascular anomalies.
Overgrowth syndromes with vascular anomalies encompass entities with a vascular anomaly as the predominant feature vs those syndromes with predominant somatic overgrowth and a vascular anomaly as a more minor component. The focus of this article is to categorize these syndromes phenotypically, including updated clinical criteria, radiologic features, evaluation, management issues, pathophysiology, and genetic information. A literature review was conducted in PubMed using key words "overgrowth syndromes and vascular anomalies" as well as specific literature reviews for each entity and supportive genetic information (e.g., somatic mosaicism). Additional searches in OMIM and Gene Reviews were conducted for each syndrome. Disease entities were categorized by predominant clinical features, known genetic information, and putative affected signaling pathway. Overgrowth syndromes with vascular anomalies are a heterogeneous group of disorders, often with variable clinical expression, due to germline or somatic mutations. Overgrowth can be focal (e.g., macrocephaly) or generalized, often asymmetrically (and/or mosaically) distributed. All germ layers may be affected, and the abnormalities may be progressive. Patients with overgrowth syndromes may be at an increased risk for malignancies. Practitioners should be attentive to patients having syndromes with overgrowth and vascular defects. These patients require proactive evaluation, referral to appropriate specialists, and in some cases, early monitoring for potential malignancies. Progress in identifying vascular anomaly-related overgrowth syndromes and their genetic etiology has been robust in the past decade and is contributing to genetically based prenatal diagnosis and new therapies targeting the putative causative genetic mutations.


Central GLP-1 receptor activation modulates cocaine-evoked phasic dopamine signaling in the nucleus accumbens core.
Drugs of abuse increase the frequency and magnitude of brief (1-3s), high concentration (phasic) dopamine release events in terminal regions. These are thought to be a critical part of drug reinforcement and ultimately the development of addiction. Recently, metabolic regulatory peptides, including the satiety signal glucagon-like peptide-1 (GLP-1), have been shown to modulate cocaine reward-driven behavior and sustained dopamine levels after cocaine administration. Here, we use fast-scan cyclic voltammetry (FSCV) to explore GLP-1 receptor (GLP-1R) modulation of dynamic dopamine release in the nucleus accumbens (NAc) during cocaine administration. We analyzed dopamine release events in both the NAc shell and core, as these two subregions are differentially affected by cocaine and uniquely contribute to motivated behavior. We found that central delivery of the GLP-1R agonist Exendin-4 suppressed the induction of phasic dopamine release events by intravenous cocaine. This effect was selective for dopamine signaling in the NAc core. Suppression of phasic signaling in the core by Exendin-4 could not be attributed to interference with cocaine binding to one of its major substrates, the dopamine transporter, as cocaine-induced increases in reuptake were unaffected. The results suggest that GLP-1R activation, instead, exerts its suppressive effects by altering dopamine release - possibly by suppressing the excitability of dopamine neurons. Given the role of NAc core dopamine in the generation of conditioned responses based on associative learning, suppression of cocaine-induced dopamine signaling in this subregion by GLP-1R agonism may decrease the reinforcing properties of cocaine. Thus, GLP-1Rs remain viable targets for the treatment and prevention of cocaine seeking, taking and relapse.


Grains are similarly categorized by 8- to 13-year-old children.
This study assessed how 8- to 13-year-old children categorized and labeled grain foods and how these categories and labels were influenced by child characteristics. The main hypotheses were that children categorized foods in consistent ways and these food categories differed from the professional food categories. A set of 71 cards with pictures and names of grain foods from eight professionally defined food groups was sorted by each child into piles of similar foods. There were 149 8- to 13-year-old children (133 English-speaking, 16 Spanish-speaking) in this exploratory study. One-way analysis of variance and Robinson matrices for identification of clusters of food items were calculated. Children created a mean (+/-standard deviation) of 8.3+/-3.8 piles with 8.6+/-9.1 cards per pile. No substantial differences in Robinson clustering were detected across subcategories for each of the demographic characteristics. For the majority of the piles, children provided "taxonomic-professional" (34.5%) labels, such as bread for the professional category of breads, rolls, and tortillas, or "script" (26.1%) labels, such as breakfast for the professional category of pancakes, waffles, and flapjacks. These categories may be used to facilitate food search in a computerized 24-hour dietary recall for children in this age group.


Immobilization of enzymes for bioremediation: A future remedial and mitigating strategy.
Over the years, extensive urbanization and industrialization have led to xenobiotics contamination of the environment and also posed a severe threat to human health. Although there are multiple physical and chemical techniques for xenobiotic pollutants management, bioremediation seems to be a promising technology from the environmental perspective. It is an eco-friendly and low-cost method involving the application of microbes, plants, or their enzymes to degrade xenobiotics into less toxic or non-toxic forms. Moreover, bioremediation involving enzymes has gained an advantage over microorganisms or phytoremediation due to better activity for pollutant degradation with less waste generation. However, the significant disadvantages associated with the application of enzymes are low stability (storage, pH, and temperature) as well as the low possibility of reuse as it is hard to separate from reaction media. The immobilization of enzymes without affecting their activity provides a possible solution to the problems and allows reusability by easing the process of separation with improved stability to various environmental factors. The present communication provides an overview of the importance of enzyme immobilization in bioremediation, carrier selection, and immobilization methods, as well as the pros and cons of immobilization and its prospects.


"Cancer risk after breast proton therapy considering physiological and radiobiological uncertainties" by Raptis et al. (Physica Medica 76 (2020) 1-6).
The paper by Raptis et al. concludes that proton therapy has an advantage over photon therapy with respect to the induction of a second cancer. Furthermore, the authors conclude that physiological movements and radiobiological parameters do not affect the general trend of lower risk associated with proton therapy. The work is based on a modeling framework which is different from most previously used models on the same subject. This invited commentary puts the findings of the paper in context with other published modeling studies on second cancer risk after proton and photon radiation therapy for breast cancer.


Analysing the Politics of Nigeria's 2019 National Minimum Wage: Towards a Public Policy.
This paper analyses the politics that characterised the Nigeria 2019 national minimum wage negotiations and implementation, which so far is the most prolonged in Nigeria's history. Workers' welfare is the responsibility of governments across the world through fixing and regulation of the national minimum wage. But in Nigeria, this has been problematic, and the entire process is characterised by industrial actions undertaken to compel the government to commit to wage negotiations and implementation. The paper argues that the absence of functional standing machinery with a focus on labour economics, deciding the condition and time for a minimum wage review is seen as the main bane in government-labour frequent face-off in Nigeria, which has negatively impacted on harmonious industrial relations. Writing from the analytical point of view, the paper finds that industrial actions have become one action too many because of government's political approach to labour demands. Deciphered in the foregoing is that the current system of government-labour negotiation for new national minimum wage cannot guarantee workers' welfare in Nigeria. Thus, for the Nigeria government to address this perennial minimum wage problem and be seen as fulfilling its obligation to the International Labour Organisation, it must urgently put in place an acceptable mechanism for fixing and regulating the national minimum wage in Nigeria to cushion the effect of the hike in petroleum products on which the national economy largely depends.


Development of the coordination between posture and manual control.
Studies have suggested that proper postural control is essential for the development of reaching. However, little research has examined the development of the coordination between posture and manual control throughout childhood. We investigated the coordination between posture and manual control in children (7- and 10-year-olds) and adults during a precision fitting task as task constraints became more difficult. Participants fit a block through an opening as arm kinematics, trunk kinematics, and center of pressure data were collected. During the fitting task, the precision, postural, and visual constraints of the task were manipulated. Young children adopted a strategy where they first move their trunk toward the opening and then stabilize their trunk (freeze degrees of freedom) as the precision manual task is being performed. In contrast, adults and older children make compensatory trunk movements as the task is being performed. The 10-year-olds were similar to adults under the less constrained task conditions, but they resembled the 7-year-olds under the more challenging tasks. The ability to either suppress or allow postural fluctuations based on the constraints of a suprapostural task begins to develop at around 10 years of age. This ability, once developed, allows children to learn specific segmental movements required to complete a task within an environmental context.


Malignant pituitary chromophobe adenoma in an infant accompanying diabetes insipidus.
This report deals with a 1.5-year-old male infant terminating in viral pneumonia and "diabetes insipidus". The autopsy revealed malignant pituitary chromophobe adenoma, invading the wall of the third ventricle, extending to the periventricular-, dorsomedial- and ventromedial area, skipping to the lateral area adjacent to the optic nerve, and permeating into the subarachnoid space of the cerebrum. At the onset of disease polydypsia and polyuria were marked followed by interstitial pneumonia with high fever, and later generalized tonic convulsion terminated in death. This case is peculiar in at least two respects. Firstly, this is the youngest reported case of malignant chromophobe adenoma. Secondly, the manifestation of diabetes insipidus is rare in chromophobe adenoma. The malignant adenoma probably occurred from the primitive gland rest of chromophobe cells in the posterior lobe becoming malignant during the course of growth development and destroyed the cells of the posterior lobe, resulting in diabetes insipidus.


Quantitation of Giardia cysts by membrane filtration.
A method of fixing and staining Giardia cysts on a membrane filter is reported. This procedure appears to be a reliable method for the recovery and detection of cysts and also for the determination of cyst densities. Evaluation and possible applications of the technique are described.


The role of motor vehicles in air pollution in the UK.
This paper presents an overview of the contribution of motor vehicles to some air pollution issues in the UK. The coverage of issues is selective concentrating primarily on the motor vehicle's role in emissions of carbon dioxide and other greenhouse gases, NOx concentrations in rural and urban areas. Finally some discussion is given of future technological developments in vehicle pollution control technology and some possible air pollution consequences.


Association of age at menarche with valvular heart disease: An analysis based on electronic health record (CREAT2109).
The association between age at menarche and coronary heart disease has been reported, but the association between age at menarche and valvular heart disease (VHD) has not been described. We aimed to examine the association between age at menarche and VHD. By collecting data from four medical centers of the Affiliated Hospital of Qingdao University (QUAH) from January 1, 2016, to December 31, 2020, we sampled 105,707 inpatients. The main outcome of this study was newly diagnosed VHD, which was diagnosed based on ICD-10 coding, and the exposure factor was age at menarche, which was accessed through the electronic health records. We used logistic regression model to investigate the association between age at menarche and VHD. In this sample (mean age 55.31 ± 13.63 years), the mean age at menarche was 15. Compared with women with age at menarche 14-15 years, the odds ratio of VHD in women with age at menarche ≤13, 16-17, and ≥18 years was 0.68 (95% CI 0.57-0.81), 1.22 (95% CI 1.08-1.38), and 1.31 (95% CI 1.13-1.52), respectively (P for all < 0.001). By restricting cubic splines, we found that later menarche was associated with increased odds of VHD (P < 0.001). Furthermore, in subgroup analysis of different etiologies, the similar trend persisted for non-rheumatic VHD. In this large inpatient sample, later menarche was associated with higher risk of VHD.


Depression and hostility in hyperprolactinemia.
1. Patients with hyperprolactinemia offer a unique opportunity to investigate the effects of prolactin on psychological states. Women with hyperprolactinemic amenorrhea rated themselves significantly more hostile, more depressed and more anxious than women with amenorrhea only and normal women. 2. The hyperprolactinemic patients were compared with a group of post-partum (7th day) women, matched for sociodemographic variables and prolactin levels. The post-partum women showed significantly less depression and anxiety than those with hyperprolactinemic amenorrhea but about the same levels of hostility. 3. Hyperprolactinemic males did not rate themselves more hostile and depressed than matched controls.


Antiatherosclerotic and antihyperlipidemic effects of octimibate sodium in rabbits.
Octimibate sodium (8-[(1,4,5-triphenyl-1H-imidazol-2-yl)oxy]octanoic acid, sodium salt; NAT 04-152) was investigated for its antihyperlipidemic and antiatherosclerotic activities in New Zealand White rabbits. Hypercholesterolemia and atherosclerosis were induced by feeding a diet containing 0.3% cholesterol for 8 weeks. In addition, repeated injections of bovine serum albumin (BSA) were used to enhance the experimental atherosclerosis. Octimibate sodium, 10.0 and 30.0 mg/kg p.o., reduced both the increase in serum cholesterol levels and the aortic plaque-formation (by about 50% in the higher dose group) as compared to control animals. Serum triglyceride levels were not influenced. Biochemical and histological examinations of the aortas showed reduced cholesterol contents in the higher dose group and a dose-dependent inhibition of pathological changes in the aortas.


Effects of chrysin, apigenin, genistein and their homoleptic copper(II) complexes on the growth and metastatic potential of cancer cells.
The (iso-)flavonoids chrysin 1, apigenin 2, genistein 3 and their homoleptic copper(II) complexes 4-6 were compared for general cancer cell growth inhibition and for antimetastatic effects on rapidly proliferating and metastasizing 518A2 melanoma cells. The complexes 4-6 were three to five times more active than the free flavonoids in cytotoxicity assays with MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] against 518A2 melanoma, HCT-116 colon, KB-V1/Vbl cervix, and MCF-7/Topo breast carcinoma cells. This activity correlated with an arrest of the cell cycle of 518A2 melanoma cells at the G2/M transition. The complexes also diminished the migration propensity of these cells in wound healing assays more distinctly than the flavonoid ligands. By fluorescent staining of F-actin and beta-catenin the antimetastatic effects of the Cu(II) genistein complex 6 were shown to originate from a remodeling of the actin cytoskeleton and an increase in cadherin-catenin complex formation, factors that favor cell-cell adhesion. Complex 6 also attenuated the expression and secretion of the metastasis-relevant matrix metalloproteinases MMP-2 and MMP-9. In summary, coordination of apigenin and genistein to Cu(II) greatly enhances the antitumoral properties of these flavonoids and potentiates their mechanistic diversity.


Mediational mechanisms involved in the relation between attachment insecurity and depression: A meta-analysis.
Several studies have investigated the intermediate variables or mediators through which attachment insecurity influence the development of depression. However, there has not been a systematic synthesis of this literature to date. The current meta-analytic review aimed at identifying such mediators and quantifying their effect size. We systematically searched Medline, Pubmed, Psycinfo, Embase, Proceedings Web of Science and ProQuest Dissertations & Theses Global up until May 2019. 108 studies met inclusion criteria (i.e., investigated intermediate variables that explain the effect of attachment insecurity [exposure] on depressive symptoms [outcome]). Standardized regression coefficients of the indirect and total paths of mediation models of 80 studies were pooled using the inverse of their variance as a weight. Studies were coded and ranked for quality. Dysfunctional attitudes (β = 0.10, 95% CI = 0.01 to 0.20), self-criticism (β = 0.17, 95% CI = 0.04 to 0.28), low self-compassion (β = 0.16, 95% CI = 0.02 to 0.29), and cognitive hyperactivating regulation strategies (β = 0.13, 95% CI = 0.05 to 0.20), such as repetitive thinking (β = 0.17, 95% CI = 0.07 to 0.28), and particularly, brooding rumination β = 0.20, 95% CI = 0.07 to 0.32), mediated the association between insecure attachment and depressive symptoms. Indirect effects were only significant among adult populations. The methodological quality of studies was mostly moderate to low and analyses revealed considerable heterogeneity. Our findings support the direct targeting of cognitive-emotional psychological mechanisms in prevention programs and treatment of depression. More longitudinal studies are needed to clarify the interplay of such mediators along with other interpersonal factors between insecure attachment and depression.


Evidence that phosphatidylcholine-specific phospholipase C is a key molecule mediating insulin-induced enhancement of gene expression from human cytomegalovirus promoter in CHO cells.
The signal transduction from insulin to its receptors and Ras has been extensively studied, while little has been reported beyond these steps. We found that the expression of human interleukin 6 gene under the control of immediate early gene promoter of human cytomegalovirus was enhanced by insulin sitmulation in Chinese hamster ovary cells. The induction effect of insulin was not significantly affected by inhibitors or activators of conventional protein kinase C, cAMP dependent protein kinase and phosphoinositide -3 kinase, however, pre-incubation of the cells with D609, a specific inhibitors of phosphatidylcholine-specific phospholipase C completely abolished the induction effect. These results clearly demonstrate that phosphatidylcholine-specific phospholipase C is a key molecule mediating insulin-induced enhancement of hIL-6 expression from the human cytomegalovirus promoter in Chinese hamster ovary cells and strongly suggest that it plays an important role in the insulin signaling pathways.Abbreviations CHO - Chinese hamster ovary; hCMV promoter - immediate early gene promoter of human cytomegalovirus; hIL-6 - human interleukin 6; PC-PLC-phosphatidylcholine-specific phospholipase C; PI-3 kinase - phosphoinositide 3 kinase; PKA - cAMP dependent protein kinase; PKC - protein kinase C.


Vaccinia virus DNA replication: a short review.
The purpose of this review is to summarize information published since 1990 on DNA replication, recombination and repair of vaccinia virus, a poxvirus. Temperature-sensitive mutations reveal four essential genes related to viral DNA replication: the E9L DNA polymerase, B1R protein kinase, D5R protein, and D4R uracil DNA glycosylase. Other proteins are likely to be also involved in viral DNA replication: the H6R DNA topoisomerase, I3L single stranded-DNA binding protein, H5R virosome-associated protein, and A50R DNA ligase. In addition, several viral-encoded proteins do regulate the level of the deoxyribonucleoside triphosphate pool: the J2R thymidine kinase, A48R thymidylate kinase, 14L and F4L subunits of ribonucleotide reductase, and F2L dUTPase. Despite the apparent simplicity of the mechanism of vaccinia virus DNA replication, several important questions related to the three Rs remain unsolved.


Interpreting time-related trends in effect estimates.
This paper reviews the sources of apparent time trends in effect. Apparent changes in effect may arise from changes in covariate distributions, background rates, exposure distribution, measurement quality, or selection factors. As with time trends in rates, time trends in effect must have at least one of these sources, since time itself has no effect. If background incidence is changing, however, time trends in effect become dependent on choice of effect measure, and interpretation must take this into account. Evidence that a trend arises from age-, cohort-, or period-related phenomena can indicate the relative plausibility of different explanations of the trend. Conversely, the relative plausibility of each explanation may indicate whether the trend is most appropriately viewed over the axis of age, birth cohort, or calendar time. Nevertheless, studies of short duration relative to an apparent trend (such as most case-control studies) must invoke strong assumptions to justify focusing on a particular axis. Illustrations are given from studies of electronic fetal monitoring and of smoking and lung cancer.


Nicotinamide mononucleotide (NMN) intake increases plasma NMN and insulin levels in healthy subjects.
Nicotinamide adenine dinucleotide (NAD+) is a coenzyme of the NAD+-dependent protein deacetylase sirtuin-1 (SIRT1). An increase in NAD+ concentration induces SIRT1 activation that results in various health benefits. Since nicotinamide mononucleotide (NMN) is a precursor of NAD+, NMN ingestion is expected to have multiple health benefits such as alleviation of aging, lifestyle-related and neurodegenerative diseases, through the activation of SIRT1. In this study, we aimed to determine the effects of daily NMN ingestion on plasma levels of NMN and NAD+. Healthy volunteers received 250 mg of NMN once a day in the morning (n = 11) for 12 weeks, and the plasma concentrations of NMN and NAD+ were measured monthly. Physiological and laboratory tests were performed within 2 h after lunch (at 2 pm) before and during NMN administration. Oral administration of NMN increased the plasma concentrations of NMN and NAD+, and the postprandial serum insulin levels. The elevation levels of NMN and insulin varied widely among individuals. No adverse symptoms were observed in the participants. Oral administration of NMN elevates plasma levels of NMN and NAD+, and postprandial serum insulin levels.


Atlantoaxial transarticular screw fixation and posterior fusion using polyester cable: a 10-year experience.
To retrospective review the clinical outcomes of the modified operative technique using a polyester suture material (Ethibond* Excel) for atlantoaxial transarticular screw fixation and posterior fusion. The retrospective reviews were conducted from 2002 to 2012. The patient's medical record reviews included demographic data, cause of atlantoaxial instability, orthopedic and surgical history, clinical presentation, radiographic finding including plain radiography, complications, operative detail, and outcome of treatment. Fusion of C1-C2 was defined as either graft consolidation or absence of C1-C2 movement on lateral flexion-extension radiograph. Twenty-three patients demonstrated clinical and radiographic evidence of atlantoaxial instability (13 men and 10 women, with a mean age of 42 years). Majority of atlantoaxial instability was caused by trauma. Most common clinical symptom was neck pain with or without cervical myelopathy. Bilateral screws were placed in 18 of the 23 patients. Five patients underwent placement of unilateral screws. The 13 patients were inserted by screws with diameter 4.0 mm. The means screw length was 40.33 mm. The means of operative time and estimated blood loss were 3.6 h and 234 ml, respectively. The mean of follow-up duration was 18 months. All 41 screws were positioned satisfactorily in C1 lateral mass. All 23 patients achieved fusion (100% fusion rate). After a period of follow-up, 9 of the 10 neurological deficit patients had completely recovered. We concluded that the atlantoaxial transarticular screw fixation and posterior fusion using polyester cable can be used for C1-2 fusion with a high fusion rate and less complications in various cases.


Improvement of inflammatory responses associated with NF-kappa B pathway in kidneys from diabetic rats.
The effects of fenofibrate on the kidneys of diabetic rats were investigated by measuring the inflammatory responses associated with transcription factor nuclear factor kappa-B (NF-kappa B) pathway. Male Wistar rats were randomly divided into 3 groups: normal control, diabetes control and diabetes + fenofibrate (10 in each group). The expression of NF-kappaB p65, plasminogen activator inhibitor-1 (PAI-1), and intercellular adhesion molecule-1 (ICAM-1) in renal cortex was detected by Western blot, RT-PCR, and immunohistochemistry, respectively. Blood lipid profiles, glucose, and urine albumin were measured as well. The expression of NF-kappa B p65, PAI-1, and ICAM-1 was significantly higher in the diabetes control than those in the normal control, and treatment with fenofibrate inhibited the increased expression of these factors in kidneys by 48.18 %, 35.04 %, and 26.41 %, respectively when compared with the diabetes control, although they were still higher in diabetes + fenofibrate than those in the normal control. Correspondingly, the profiles of lipid were significantly elevated in the diabetes control compared with the normal control, and decreased significantly in diabetes + fenofibrate. Fenofibrate exhibited a downregulating effect on the NF-kappa B pathway in diabetic kidneys, implying that fenofibrate could be a potential treatment for diabetic nephropathy.


Toll-like Receptor 9 Signaling Is Augmented in Systemic Sclerosis and Elicits Transforming Growth Factor β-Dependent Fibroblast Activation.
Although transforming growth factor β (TGFβ) is recognized as being a key trigger of fibroblast activation in systemic sclerosis (SSc), prominent innate immunity suggests that additional pathways contribute to disease persistence. Toll-like receptor 9 (TLR9) is implicated in autoimmunity and fibrosis; however, the expression, mechanism of action, and pathogenic role of TLR9 signaling in SSc remain uncharacterized. The aim of this study was to explore the expression, activity, and potential pathogenic role of TLR9 in the context of skin fibrosis in SSc and in mouse models of experimental fibrosis. Expression and localization of TLR9 were evaluated in SSc skin biopsy specimens and explanted skin fibroblasts. Fibrotic responses elicited by type A CpG oligonucleotide and mitochondrial DNA (mtDNA) were examined in human skin fibroblasts by a combination of real-time quantitative polymerase chain reaction, Western blot analysis, transient transfection, immunofluorescence microscopy, and functional assays. Expression of TLR9 was examined in 2 distinct mouse models of experimental fibrosis. Skin biopsy specimens obtained from 2 independent cohorts of SSc patients showed up-regulation of TLR9, and myofibroblasts were the major cellular source. Moreover, SSc skin biopsy specimens showed evidence of TLR9 pathway activation. CpG induced robust TLR9-dependent fibrotic responses in explanted normal fibroblasts that could be blocked by bortezomib and were mediated through the action of endogenous TGFβ. Mice with experimental fibrosis showed a time-dependent increase in TLR9 localized primarily to myofibroblasts in the dermis. In isolated fibroblasts, TLR9 elicits fibrotic responses mediated via endogenous TGFβ. In patients with SSc, mtDNA and other damage-associated TLR9 ligands in the skin might trigger localized activation of TLR9 signaling, TGFβ production, and consequent fibroblast activation. Disrupting this fibrotic process with inhibitors targeting TLR9 or its downstream signaling pathways might therefore represent a novel approach to SSc therapy.


A review of the biological effects of total sleep deprivation in man.
This biologically oriented review attempts to complement earlier and more psychological performance based reviews of total sleep deprivation. Also, the effects of total sleep deprivation are interpreted, here, from a function of human sleep perspective, rather than from the more usual stress viewpoint. It would appear that total sleep deprivation does not produce any major changes in biochemical and physiological measures of somatic functioning. Such a conclusion would not seem to support an hypothesis that human sleep is for body restitution. Although there are equivocal results amongst several of the more psychophysiological measures, EEG does show a pronounced change. This latter finding, together with many reports of psychological performance detriment, would appear to sustain a CNS or cerebral restitutional role for human sleep. However, before definitive conclusions can be drawn from the biochemical and physiological findings of total sleep deprivation, the following qualifications of experimental methodology are made: (1) Apart from sleep loss, many studies have provided unnatural regimes which may have ameliorated possible effects of total sleep deprivation. (2) Most studies are of relatively short duration and may not have been sufficiently long for effects to develop. (3) Measures are often limited in range and depth of analysis. (4) Subjects are mostly fit, young adult, intelligent males and there is little constitutional variability. (5) Reported changes of statistical significance may be of no physiological significance and changes of possible physiological significance may be obscured by statistical procedures. (6) Intervening behavioural variables, such as novelty and anticipation of the sleep deprivation situation, may confound real effects.


Generation of crossreacting tumor antigens in ascitic derivatives from murine methylcholanthrene-induced sarcomas.
Sarcomas induced by the chemical carcinogen 3-methyl-cholanthrene (MC) in pedigreed BALB/c strain mice were studied for the existence and characteristics of tumor-specific antigens that induce protective immune defenses in syngeneic mice (TATA). It was found that each of the neoplasms expressed a unique immunogenicity that was stable and heritable over a period of 125 transfers in vivo. Common or crossreacting TATA were not observed. When converted to an ascitic form, two of these sarcomas, CII-7 and CII-10, were found to be crossreactive, presumably sharing TATA with each other and with the MC-induced sarcoma Meth A. Two other neoplasms converted to the ascitic form, however, retained their unique TATA. Although the precise nature of unique and crossreacting TATA is not known, it is hoped that recent investigations in the purification of TATA of chemically induced neoplasms will shed light on the mechanisms responsible for the diversity of tumor-specific antigens.


Field-amplified sample injection in capillary zone electrophoresis for the pharmacokinetic research of trace risperidone and its major metabolite 9-hydroxyrisperidone in beagle dogs.
This article describes a method for the simultaneous quantitation of risperidone and its major metabolite, 9-hydroxyrisperidone, in beagle dog plasma by field-amplified sample injection in capillary zone electrophoresis. The separation was carried out at 25°C in a 48 cm × 75 µm fused-silica capillary with an applied voltage of 20 kV using 60 mM NaH2 PO4 buffer (pH 3.6). The detection wavelength was 280 nm. Clean-up and preconcentration of plasma samples were conducted by 96-well formatted liquid-liquid extraction. In this study, this stacking technique provided a sensitivity enhancement of approximately 158 to 188 fold compared with the same sample without stacking. The method was suitably validated with respect to stability, specificity, linearity, lower limit of quantitation, accuracy, precision, and extraction recovery. Calibration curves exhibited good linearity (r2 > 0.995) over a wide concentration range of 2.5 to 200 ng/mL for both risperidone and 9-hydroxyrisperidone. The intra- and interday precisions at the three quality control levels were less than 11.40%. The intra- and interday accuracies ranged from 87.90 to 107.17% for risperidone and from 88.43 to 105.92% for 9-hydroxyrisperidone. All validation data were within the required limits. In conclusion, the method developed was successfully applied to pharmacokinetic studies of risperidone and 9-hydroxyrisperidone in beagle dogs.


Rimegepant Orally Disintegrating Tablet for Acute Migraine Treatment: A Review.
To review the pharmacology, pharmacokinetics, efficacy, safety, and place in therapy of rimegepant for treatment of migraine. A comprehensive PubMed and Cochrane search (1985 to May 2020) was performed utilizing the keywords rimegepant, Nurtec, orally disintegrating tablet, migraine, migraine headache, migraine disorder, calcitonin gene-related peptide, and calcitonin gene-related peptide antagonist. Additional data were obtained from the references of identified articles, manufacturer's product labeling and website, ClinicalTrials.gov, and governmental sources. All English-language trials evaluating oral rimegepant were included for this review. Rimegepant orally disintegrating tablet (ODT) is Food and Drug Administration approved for the treatment of migraine. According to data from 3 phase 3 randomized controlled trials, rimegepant has been shown to significantly improve freedom from pain at 2 hours after the dose and freedom from the most bothersome symptom 2 hours postdose. Additional outcomes improved include freedom from photophobia and phonophobia at 2 hours postdose and pain relief 2 hours after the dose. Adverse effects of rimegepant include nausea, urinary tract infection, and dizziness. Orally disintegrating rimegepant provides a novel mechanism of action for the treatment of acute migraine. When patients experience inadequate relief from other therapies, have contraindications to triptans, or are unable to tolerate the adverse effects of triptans, rimegepant is a promising therapeutic option. Rimegepant ODT is an efficacious migraine treatment option with a novel mechanism of action, convenient dosage form, and limited adverse effect profile.


Correlation between clinical features and circulating levels of soluble intercellular adhesion molecule-1 in Hodgkin's disease.
Previous reports have suggested soluble intercellular adhesion molecule-1 as a marker of disease activity in Hodgkin's disease. In the present study we investigated serum levels of intercellular adhesion molecule-1 at diagnosis in 104 patients with Hodgkin's disease and in 77 of these patients following the achievement of complete remission (within 12 months of diagnosis). Mean serum levels at diagnosis were significantly higher in patients than in controls (P < 0.0001) and were related to advanced stages of disease (P = < 0.0001), presence of "B" symptoms (P < 0.0001), abnormality of laboratory indexes (P < 0.0001), erythrocyte sedimentation rate values (r = 0.41, P < 0.0001) and serum levels of soluble interleukin-2 receptor alpha chain (r = 0.51, P < 0.0001). Mean values in complete remission were significantly lower than at diagnosis (P = 0.003). Lower mean values at diagnosis were detected in 30 patients with advanced disease who attained complete remission, compared with 6 patients who failed to attain complete remission with standard treatment. We conclude that in Hodgkin's disease, high serum levels of soluble intercellular adhesion molecule-1 are detectable at presentation and strictly correlate with some clinical features. Response to treatment is paralleled by reduced serum levels. Larger prospective studies are needed to evaluate the possible prognostic significance of serum levels of soluble intercellular adhesion molecule-1 at diagnosis.


The degradation of guar gum by a faecal incubation system.
1. Homogenized and diluted faeces (50 g/l) from one human source were incubated with the complex plant polysaccharide, guar gum, to investigate the degradation of viscous polysaccharides by intestinal bacteria. 2. Incubation of the faecal homogenate with guar gum produced a rapid decrease in viscosity and in pH, accompanied by the release of hydrogen. 3. No changes in viscosity or pH were observed and there was no production of H2 gas when guar gum was incubated with autoclaved faecal homogenate (20 min, 1.03 x 10(5) Pa). 4. A bacteria-free filtrate of faeces was prepared by centrifuging the faecal homogenate (2400 g for 100 min) followed by filtration through a Seitz filter and then a millipore filter (size 0.45 micron). Incubating this with guar gum produced a slow decrease in viscosity, but no significant change in pH and no generation of H2. 5. Our results show that guar gum can be fermented by human colonic bacteria and suggest the possibility of predigestion by extracellular free enzymes.


Ni2P nanocrystals embedded Ni-MOF nanosheets supported on nickel foam as bifunctional electrocatalyst for urea electrolysis.
It's highly desired but challenging to synthesize self-supporting nanohybrid made of conductive nanoparticles with metal organic framework (MOF) materials for the application in the electrochemical field. In this work, we report the preparation of Ni2P embedded Ni-MOF nanosheets supported on nickel foam through partial phosphidation (Ni2P@Ni-MOF/NF). The self-supporting Ni2P@Ni-MOF/NF was directly tested as electrode for urea electrolysis. When served as anode for urea oxidation reaction (UOR), it only demands 1.41 V (vs RHE) to deliver a current of 100 mA cm-2. And the overpotential of Ni2P@Ni-MOF/NF to reach 10 mA cm-2 for hydrogen evolution reaction HER was only 66 mV, remarkably lower than Ni2P/NF (133 mV). The exceptional electrochemical performance was attributed to the unique structure of Ni2P@Ni-MOF and the well exposed surface of Ni2P. Furthermore, the Ni2P@Ni-MOF/NF demonstrated outstanding longevity for both HER and UOR. The electrolyzer constructed with Ni2P@Ni-MOF/NF as bifunctional electrode can attain a current density of 100 mA cm-2 at a cell voltage as low as 1.65 V. Our work provides new insights for prepare MOF based nanohydrid for electrochemical application.


Effect of rapamycin on lysosomal accumulation in a CRISPR/Cas9-based cellular model of VPS13A deficiency.
VPS13A is a lipid transfer protein localized at different membrane contact sites between organelles, and mutations in the corresponding gene produce a rare neurodegenerative disease called chorea-acanthocytosis (ChAc). Previous studies showed that VPS13A depletion in HeLa cells results in an accumulation of endosomal and lysosomal markers, suggesting a defect in lysosomal degradation capacity leading to partial autophagic dysfunction. Our goal was to determine whether compounds that modulate the endo-lysosomal pathway could be beneficial in the treatment of ChAc. To test this hypothesis, we first generated a KO model using CRISPR/Cas9 to study the consequences of the absence of VPS13A in HeLa cells. We found that inactivation of VPS13A impairs cell growth, which precludes the use of isolated clones due to the undesirable selection of edited clones with residual protein expression. Therefore, we optimized the use of pool cells obtained shortly after transfection with CRISPR/Cas9 components. These cells are a mixture of wild-type and edited cells that allow a comparative analysis of phenotypes and avoids the selection of clones with residual level of VPS13A expression after long-term growth. Consistent with previous observations by siRNA inactivation, VPS13A inactivation by CRISPR/Cas9 resulted in accumulation of the endo-lysosomal markers RAB7A and LAMP1. Notably, we observed that rapamycin partially suppressed the difference in lysosome accumulation between VPS13A KO and WT cells, suggesting that modulation of the autophagic and lysosomal pathway could be a therapeutic target in the treatment of ChAc.


Posterior reversible encephalopathy syndrome revealing Takayasu's arteritis in a child.
Posterior Reversible Encephalopathy Syndrome (PRES) is a rare complication of Takayasu's Arteritis. We report the case of an 11-year-old girl who presented with a tonic-clonic seizure and loss of consciousness, without fever. Imaging revealed characteristic white matter edema of the occipital and parietal lobes, in keeping with PRES. Further imaging demonstrated right renal artery stenosis and wall thickening of the abdominal aorta. The combination of hypertension, the discrepancy of blood pressure recordings between upper limbs, and imaging abnormalities of the aorta and the left renal artery led to the diagnosis of PRES secondary to Takayasu's Arteritis. Treatment with oral corticosteroids, azathioprine, amlodipine, and propranolol resulted in the complete resolution of the patient's symptoms and imaging abnormalities.


Kampo medicines for gastrointestinal tract disorders: a review of basic science and clinical evidence and their future application.
Treatment with kampo, the Japanese traditional medicine, is a form of pharmacological therapy that combines modern Western and traditional Asian medical practices. In Japan, various traditional medicines are often combined with Western medicines and prescribed for patients with diseases such as gastroesophageal reflux disease, functional dyspepsia, chronic gastritis, irritable bowel syndrome, and post-operative ileus. Based on numerous past observations, Japanese traditional medicines are thought to be particularly useful in the treatment of medically unexplained physical symptoms such as nausea, abdominal discomfort, and anorexia. However, the detailed mechanism by which they mediate their pharmacological action is yet unknown. In addition, the clinical evidence to support their use is insufficient. This review focuses on the basic evidence of the pharmacological action and the clinical efficacies of kampo medicines accumulated over several past decades. In addition, we introduce both the current novel insights into kampo medicines and the therapeutic approach employed when they are used to treat various disorders of the gastrointestinal tract.


Percutaneous puncture of abdominal cystic masses in children.
A technique of percutaneous puncture and opacification of cystic abdominal masses is outlined, and its diagnostic and therapeutic potential demonstrated in a series of 16 masses in 15 children. It is suggested as an alternative to ultrasound and computed tomography in certain situations.


Complete genome sequence of human pathogen Kosakonia cowanii type strain 888-76T.
Kosakonia cowanii type strain 888-76T is a human pathogen which was originally isolated from blood as NIH group 42. In this study, we report the complete genome sequence of K. cowanii 888-76T. 888-76T has 1 chromosome and 2 plasmids with a total genome size of 4,857,567bp and C+G 56.15%. This genome sequence will not only help us to understand the virulence features of K. cowanii 888-76T but also provide us the useful information for the study of evolution of Kosakonia genus.


Prevalence and risk factors for postpartum depressive symptoms among women enrolled in WIC.
The objectives of this study were to determine the prevalence and correlates of postpartum depressive symptoms (PDS) among women with a recent live birth and specifically among women participating in and eligible for the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC). Pregnancy Risk Assessment and Monitoring System data from 22 states in 2006-2008 (n = 75,234) were used to estimate the prevalence of PDS using a two-question screener. Associations between PDS and respondent demographics, risk factors and behaviors, and WIC program eligibility and participation were assessed using logistic regression. Overall prevalence of PDS was 13.8 %:19.8 % among WIC participants, 16.3 % among non-participants eligible for WIC, and 6.8 % of women not eligible for the program. PDS prevalence was higher among younger, less educated, and poorer women, as well as those engaging in risky behaviors during pregnancy (smoking and binge drinking), and those with an unintended pregnancy and who experienced intimate partner violence during pregnancy. Controlling for these factors, the odds of PDS were no different between WIC participants and women eligible but not participating in the program (aOR 1.08, 95 % CI 0.97-1.22), but WIC enrollees were significantly more likely than ineligible women to report PDS (aOR 1.65, 95 % CI 1.39-1.95). WIC serves more than 1 million pregnant women each year, one-fifth of whom may experience PDS. WIC has a unique opportunity to screen and provide referrals to new mothers receiving postpartum WIC benefits.


Adjuvant vinblastine, actinomycin D, bleomycin, cyclophosphamide and cis-platinum chemotherapy regimen with and without maintenance in patients with resected stage IIB testis cancer.
A total of 42 patients with stage IIB nonseminomatous germ cell tumors of the testis after orchiectomy and retroperitoneal lymph node dissection received adjuvant chemotherapy with the modified vinblastine, actinomycin D, bleomycin, cyclophosphamide and cis-platinum regimen. Of the patients 29 had N2B and 13 had N3 nodal categories. Adjuvant vinblastine, actinomycin D, bleomycin, cyclophosphamide and cis-platinum chemotherapy was given with maintenance in the first 24 patients and without maintenance (2 months of chemotherapy) in the subsequent 18. Chemotherapy with maintenance was given for 1 year and began with 2 inductions 3 to 4 weeks apart: 600 mg./m.2 intravenous cyclophosphamide, 30 mg. intravenous bleomycin, 1 mg./m.2 intravenous actinomycin D and 4 mg./m.2 intravenous vinblastine on day 1, 20 mg./m.2 bleomycin daily by continuous 24-hour induction on days 1 to 3 and 120 mg./m.2 intravenous cis-platinum with mannitol-induced diuresis on day 4. Maintenance with 6 mg./m.2 intravenous vinblastine and 1 mg./m.2 intravenous actinomycin D every 3 weeks was initiated 3 weeks after the second induction for the remainder of the year. Adjuvant vinblastine, actinomycin D, bleomycin, cyclophosphamide and cis-platinum chemotherapy without maintenance was given for 2 months and used 3 inductions identical to those described previously. Complete remission has been maintained in 41 of 42 patients: all 24 who received maintenance chemotherapy and 17 of 18 who did not. One patient had a relapse with sarcoma and 6 required broad-spectrum antibiotics for fever during myelosuppression. A temporary increase in the serum creatinine of more than 2 mg. per cent occurred in 1 patient. Chronic renal failure or pulmonary fibrosis was not seen. Our results show that vinblastine, actinomycin D, bleomycin, cyclophosphamide and cis-platinum chemotherapy is effective in the prevention of recurrences in patients with resected stage IIB disease, and suggest that adjuvant chemotherapy is equally effective with or without maintenance.


A possible explanation of sudden infant death syndrome (SIDS).
Research into (lucid) dreaming has shown that the images of a dream are supported by the corresponding body actions, utilizing those muscles which remain active during dreaming. We suggest that Sudden Infant Death Syndrome (SIDS) or Cot Death may be a result of an infant dreaming about its life as a fetus. In the course of that dream, since a fetus does not breathe in the usual sense, the infant may cease to breathe and die. Our hypothesis is consistent with the known facts about SIDS, including social factors such as sleeping position and climatic variation. We suggest that the risk of SIDS can be reduced by making the environment of the infant, as much as possible, unlike that of the womb.


Learning, attention/hyperactivity, and conduct problems as sequelae of excessive daytime sleepiness in a general population study of young children.
Although excessive daytime sleepiness (EDS) is a common problem in children, with estimates of 15%; few studies have investigated the sequelae of EDS in young children. We investigated the association of EDS with objective neurocognitive measures and parent reported learning, attention/hyperactivity, and conduct problems in a large general population sample of children. Cross-sectional. Population based. 508 children from The Penn State Child Cohort. N/A. Children underwent a 9-h polysomnogram, comprehensive neurocognitive testing, and parent rating scales. Children were divided into 2 groups: those with and without parent-reported EDS. Structural equation modeling was used to examine whether processing speed and working memory performance would mediate the relationship between EDS and learning, attention/hyperactivity, and conduct problems. Logistic regression models suggest that parent-reported learning, attention/hyperactivity, and conduct problems, as well as objective measurement of processing speed and working memory are significant sequelae of EDS, even when controlling for AHI and objective markers of sleep. Path analysis demonstrates that processing speed and working memory performance are strong mediators of the association of EDS with learning and attention/hyperactivity problems, while to a slightly lesser degree are mediators from EDS to conduct problems. This study suggests that in a large general population sample of young children, parent-reported EDS is associated with neurobehavioral (learning, attention/hyperactivity, conduct) problems and poorer performance in processing speed and working memory. Impairment due to EDS in daytime cognitive and behavioral functioning can have a significant impact on children's development.


The relationships between measures of stature recovery, muscle activity and psychological factors in patients with chronic low back pain.
Individuals with low back pain (LBP) often exhibit elevated paraspinal muscle activity compared to asymptomatic controls during static postures such as standing. This hyperactivity has been associated with a delayed rate of stature recovery in individuals with mild LBP. This study aimed to explore this association further in a more clinically relevant population of NHS patients with LBP and to investigate if relationships exist with a number of psychological factors. Forty seven patients were recruited from waiting lists for physiotherapist-led rehabilitation programmes. Paraspinal muscle activity while standing was assessed via surface electromyogram (EMG) and stature recovery over a 40-min unloading period was measured on a precision stadiometer. Self-report of pain, disability, anxiety, depression, pain-related anxiety, fear of movement, self-efficacy and catastrophising were recorded. Correlations were found between muscle activity and both pain (r=0.48) and disability (r=0.43). Muscle activity was also correlated with self-efficacy (r=-0.45), depression (r=0.33), anxiety (r=0.31), pain-related anxiety (r=0.29) and catastrophising (r=0.29) and was a mediator between self-efficacy and pain. Pain was a mediator in the relationship between muscle activity and disability. Stature recovery was not found to be related to pain, disability, muscle activity or any of the psychological factors. The findings confirm the importance of muscle activity within LBP, in particular as a pathway by which psychological factors may impact on clinical outcome. The mediating role of muscle activity between psychological factors and pain suggests that interventions that are able to reduce muscle tension may be of particular benefit to patients demonstrating such characteristics, which may help in the targeting of treatment for LBP.


History of heart-lung transplantation.
Over the next few years we will see expanded application of the single lung transplant. At the moment domino procedure, with its advantage of very reliable tracheal healing, has the advantage over the double lung operation. We would expect routine use of the heart from those heart-lung recipients with anything more than moderately impaired cardiac function.


Static FET-PET and MR Imaging in Anaplastic Gliomas (WHO III).
O-(2-[18F]-fluoroethyl)-L-tyrosine-positron emission tomography (FET-PET) imaging is an additional tool for tumor grading and surgery planning. Up to now, not much is known about FET-PET imaging in anaplastic gliomas. Our objective was to assess the FET uptake in anaplastic gliomas, compared with magnetic resonance imaging (MRI), histopathologic markers, and its prognostic value. Forty-six patients (27 males/19 females) with an anaplastic glioma (WHO III) who received MRI and FET-PET imaging before surgery were retrospectively analyzed. Tumor volume was calculated in MRI and FET-PET imaging using a tumor-to-background ratio (TBR), and maximum FET uptake (TBRmax) was calculated. Overall survival (OS) and histopathologic markers (isocitrate-dehydrogenase 1/2-mutation, oligodendrial differentiation, and Ki67 proliferation index) were assessed. Univariate and multivariate analysis was performed for OS. In univariate analysis a significant correlation of TBRmax to OS was observed (P = 0.031). Tumor volume in FET-PET imaging (TBR > 2.0) (P = 0.028) showed a higher correlation to OS than the volume of the contrast-enhancing tumor part (P = 0.031). The highest correlation was observed for intersection of volume TBR > 1.3 and the volume of the contrast-enhancing tumor part (P = 0.005); fluid-attenuated inversion recovery volume showed no significant correlation to OS (P = 0.401) in the univariate analysis. Anaplastic glioma with oligodendrial differentiation showed significantly higher TBRmax values (P = 0.029), while no significant difference was observed for isocitrate hydrogenase 1/2-mutation (P = 0.752). Static FET-PET provides significant prognostic information in anaplastic gliomas, which adds to the value of MRI, supporting the use of both modalities preoperatively to assess individual risks and estimate prognosis. Definition of the histopathologic subtype using static FET-PET remains challenging.


Peridialysis BP levels and risk of all-cause mortality: a dose-response meta-analysis.
Blood pressure (BP) management posed great challenge in hemodialysis (HD) population. We conducted a dose-response meta-analysis to investigate the quantitative features and the potential threshold effect of the associations between peridialysis BP levels and all-cause mortality risk in HD population. We searched all of the prospective cohort studies (published before 18 March 2017) on the associations between peridialysis BP levels and all-cause mortality risk. A total of 229,688 prevalent HD patients from 8 studies were included. Significant non-linear associations were noted between peridialytic BP levels and all-cause mortality risk. Significant increased risk of death was found in four peridialysis BP ranges, that is, low levels of predialysis SBP (<135 mmHg, 140 mmHg as the reference), two extremes of predialysis DBP (<55 and >95 mmHg, 90 mmHg as the reference), high levels of postdialysis SBP (>180 mmHg, 130 mmHg as the reference), and low levels of postdialysis DBP (<75 mmHg, 80 mmHg as the reference). Threshold effect was determined in the associations between peridialysis BP and all-cause mortality risk, and potential BP thresholds were identified (149 mmHg for predialysis SBP, 79 mmHg for predialysis DBP, 147 mmHg for postdialysis SBP and 76 mmHg for postdialysis DBP). In conclusion, the proposed peridialysis BP ranges and the threshold values could help clinicians identify high risk HD patients. The interpretation of the peridialysis BP mortality associations should be based on the features of HD population (especially the cardiovascular conditions, volume status and the dialysis vintage).