[Glycoprotein components of the skin under normal conditions and in several types of pathology].
Content of sialic acids was increased 2.9-3.4-fold in soluble fraction of pathologically altered skin (parakeratotoic scales in psoriasis and allergo dermatoses) as compared with a skin of healthy persons. In parakeratotic scales 7-11 zones of PAS (positive glycoproteins) were found by polyacrylamide gel disc electrophoresis; they occurred in skin of healthy persons only in several cases. Hemoglobin-binding activity (haptoglobin) was observed in pathologically altered skin of 64-93% patients with psoriasis; it was not found in healthy persons. The spectrum of haptoglobin fractions in skin correlated with its phenotype in blood.


Humic-like substances extracted from composts can promote the photodegradation of Irgarol 1051 in solar light.
Humic-like substances (HLS) were extracted from a mixture of sewage sludges and trimmings (70-30%, w/w) after different times of composting (0, 70 days and 130 days). HLS were analyzed by elemental analysis, UV-visible and fluorescence spectroscopy and also tested for their ability to photosensitize the degradation of Irgarol. The rate of Irgarol photodegradation in artificial solar light was found to be 2.5- to 4.3-fold higher in the presence of HLS than in buffered Milli-Q water. These results were confirmed by experiments in solar light that evidenced the photodegrading properties of HLS in a more striking way. Using 2-propanol as hydroxyl radical scavenger, we could show that hydroxyl radicals contributed to the photosensitized Irgarol degradation for about 25%. The photodegrading activity of HLS, their absorbance and their emissive properties were all found to increase between 0 and 70 days of composting and to remain quite constant between 70 and 130 days. The degree of humification varied in the same way, linking all these properties to the humification process.


Lymphadenopathy in connection with human herpes virus type 6 (HHV-6) infection.
Two siblings and their mother developed afebrile generalized lymphadenopathy. The lymph nodes were movable and painless. During the course of the illness, the mother and one child developed an uncharacteristic rash. Increased titers of human herpes virus type 6 (HHV-6) antibodies were found in all three family members and in an unrelated patient with lymphadenitis colli. The enlarged lymph nodes decreased in size within several weeks. We speculate these symptoms to be caused by an infection with this lymphotropic virus.


Peanut lectin histochemistry of 120 mammary carcinomas and its relation to tumor type, grading, staging, and receptor status.
Peanut lectin (PNL) is known to bind beta-D-galactosyl-(1-3)-N-acetyl-D-galactosamine, which provides antigenic determination of the Thomsen-Friedenreich antigen ( TFAg ). The aim of this study was to analyse the expression of peanut lectin binding sites in mammary carcinomas and to correlate these with tumor type, histological grading, staging and biochemical receptor status. The series comprised 120 invasive mammary carcinomas and 14 cases with normal breast tissue or benign epithelial proliferations as controls. In controls mainly luminal or apical PNL-binding was discovered, however, in all except three carcinomas a cytoplasmatic localisation of TFAg with three major patterns was found: diffuse, granular-globular and vacuolar reactions. The quantitative-qualitative evaluation of the PNL-staining revealed a statistically significant correlation between globular-vacuolar PNL-reaction and tumor type with a higher percentage of this type of reaction in invasive lobular carcinomas as opposed to tubular and invasive ductal carcinomas. Furthermore a statistically significant relationship was disclosed between PNL- histopositivity and estrogen positive - progesterone positive cases. However, the findings of contradictory PNL-status and hormone-receptor status illustrates clearly the difficulty of predicting the biochemical receptor status. No correlation was found between PNL-histochemistry, histological grading, and pathological staging. The practical implications of PNL-histochemistry of mammary carcinomas are discussed.


Exploring Hikikomori-like idiom of distress a year into the SARS-CoV-2 pandemic in Oman: Factorial validity of the 25-item Hikikomori Questionnaire, prevalence and associated factors.
Existing literature that examines the Hikikomori-like idiom of distress (HLID) initially labelled this phenomenon as a culture-bound syndrome. However, the increasing number of reports from other parts of the world suggest that HLID could instead be a culture-reactive idiom of distress, originating from biopsychosocial disequilibrium and cultural upheaval. The impact of imposed social withdrawal due to the Coronavirus 2 severe acute respiratory syndrome (SARS-CoV-2) pandemic on the growing prevalence of HLID has not yet been adequately explored. Aims: The first objective is to examine the factorial validity of the 25-item Hikikomori Questionnaire (HQ-25) in Oman. Second, we aimed to investigate the prevalence of HLID following the lifting of SARS-COV-2 restrictions in the Arabian Gulf country of Oman. The third related objective is to examine factors associated with the variation of HLID. This cross-sectional online survey was widely distributed across the diverse socio-demographic population residing in Oman. After the validation of the questionnaire and the factorial validity, the Arabic version of HQ-25 was used to explore the prevalence and factors associated with HLID. A total of 1529 participants were included in the study (response rate = 76.5%), of whom 44% (n = 673) expressed HLID. We randomly split it into half, one for exploratory factor analysis (EFA) (n = 764) and the other half for confirmatory factor analysis (CFA) (n = 765). From the EFA results, a three-factor model was found for the Omani version of HQ-25, which represented 52.87% of the variance with good internal reliability (Overall Cronbach's: 0.92; Socialisation: 0.92; Isolation: 0.84; Emotional support: 0.73). The CFA results report acceptable goodness-of-fit indices (χ2/df = 17.92, p < .001; CFI = 0.90; TLI = 0.95; RMSEA = 0.04, 95% CI 0.02-0.07; SRMR = 0.05) of the three-factor model of the collected samples. All 1529 data were used in the respondents. The results of the logistic regression showed that married marital status (OR = 1.51, 95% CI: 1.12-2.03, p = 0.007), older age (OR = 0.97, 95% CI: 0.95-0.99, p = 0.008), living in an urban area (OR = 0.71, 95% CI: 0.56-0.91, p = 0.006), unemployed occupational status (OR = 1.72, 95% CI: 1.30-2.88, p < .001), screen time (7+ hours vs. <4 hours: OR = 4.50, 95% CI: 3.16-6.41, p < .001; 4-7 hours vs. <4 hours: OR = 2.10, 95% CI: 1.61-2.70, p < .001), history of mental illness (OR = 3.70, 95% CI: 2.29-5.91, p < .001), and adverse childhood experiences (OR = 2.60, 95% CI: 2.03-3.20, p < .001) were significant risk factors for HLID. The factorial validity of the HQ-25 performed in this study appears to mirror the previously reported 3-factor structures. Some of the associated factors appear to support and, conversely, dissent from the findings of previous studies. These are discussed in terms of the attributions of the SARS-COV-2 pandemic, demographic trends in Oman, and sociocultural factors specific to the region of interest.


Saccharomyces cerevisiae fungemia with granulomas in the bone marrow in a patient undergoing BMT.
A 48-year-old woman underwent allogeneic BMT for CML in chronic phase. One day +180 she experienced fever (37.8 degrees C) and skin rash. Blood cultures from the Hickman catheter and peripheral veins were positive for Saccharomyces cerevisiae. The clinical course of this patient indicates that Saccharomyces should be considered as a possible cause of fever of otherwise unknown origin.


Engineering osteogenic microenvironments by combination of multilayers from collagen type I and chondroitin sulfate with novel cationic liposomes.
Cationic liposomes composed of a novel lipid (N-{6-amino-1-[N-(9Z) -octadec9-enylamino] -1-oxohexan-(2S) -2-yl} -N'- {2- [N, N-bis(2-aminoethyl) amino] ethyl} -2-hexadecylpropandiamide) (OO4) and dioleoylphosphatidylethanolamine (DOPE) possess high amounts of amino groups and are promising systems for lipofection. Moreover, these cationic liposomes can also be used as a polycationic entity in multilayer formation using layer-by-layer technique (LbL), which is a method to fabricate surface coatings by alternating adsorption of polyanions and polycations. Since liposomes are suitable for endocytosis by or fusion with cells, controlled release of their cargo on site is possible. Here, a polyelectrolyte multilayer (PEM) system was designed of chondroitin sulfate (CS) and collagen type I (Col I) by LbL technique with OO4/DOPE liposomes embedded in the terminal layers to create an osteogenic microenvironment. Both, the composition of PEM and cargo of the liposomes were used to promote osteogenic differentiation of C2C12 myoblasts as in vitro model. The internalization of cargo-loaded liposomes from the PEM into C2C12 cells was studied using lipophilic (Rhodamine-DOPE conjugate) and hydrophilic (Texas Red-labeled dextran) model compounds. Besides, the use of Col I and CS should mimic the extracellular matrix of bone for future applications such as bone replacement therapies. Physicochemical studies of PEM were done to characterize the layer growth, thickness, and topography. The adhesion of myoblast cells was also evaluated whereby the benefit of a cover layer of CS and finally Col I above the liposome layer was demonstrated. As proof of concept, OO4/DOPE liposomes were loaded with dexamethasone, a compound that can induce osteogenic differentiation. A successful induction of osteogenic differentiation of C2C12 cells with the novel designed liposome-loaded PEM system was shown. These findings indicate that designed OH4/DOPE loaded PEMs have a high potential to be used as drug delivery or transfection system for implant coating in the field of bone regeneration and other applications.


Biochemical validation of self-reported exposure to environmental tobacco smoke.
Biochemical validation of reported exposure to environmental tobacco smoke (ETS) lends credibility to epidemiological studies investigating the association of passive inhalation of smoke to respiratory disease or lung cancer. In the current study, a series of questions regarding ETS exposure was self-administered to nonsmokers and self-reported intensity of exposure was compared with cotinine levels in urine samples obtained on site. The target population of this study was a group of municipal workers who reported exposure in a domestic setting and/or in the workplace. When asked if they were exposed to ETS on social occasions, both males and females who responded positively had higher urinary cotinine levels (P less than 0.02) than those who gave a negative response. Mean urinary cotinine concentrations were found to be elevated in both men and women who reported that they lived with a smoker. Cotinine levels in the urine of those reporting exposure were over twice as high as those in the urine of respondents who denied having been exposed. ETS exposure in the home was the greatest contributor to increased urinary cotinine levels in both men and women. Among individuals who were exposed at work only, the reported degree of exposure agreed well with the mean urinary cotinine values. Those findings emphasize that the validation of exposure status with a biomarker is an essential prerequisite for epidemiological studies investigating passive smoking.


Probing Network Mechanisms of Brain Stimulation in the Mood Circuit.
Direct brain stimulation has diverse effects on network activity. In this issue of Neuron, Qiao et al. (2020) demonstrate a novel approach for using stimulation to characterize and modulate interactions between areas of the mood processing network.


Lipolysis products promote the formation of complexes of very-low-density and low-density lipoproteins.
In the course of lipolysis, surface lipid products may accumulate on very-low-density lipoproteins (VLDL). To investigate potential lipoprotein interactions mediated by such products, radiolabeled low-density lipoproteins (LDL) were incubated with VLDL and bovine milk lipoprotein lipase in the presence of limited free fatty acid acceptor. With partial VLDL degradation, association of radiolabeled LDL with VLDL remnants or larger aggregates of VLDL density was demonstrated by gradient gel electrophoresis, agarose chromatography, and density gradient ultracentrifugation. VLDL-LDL complex formation was also observed in incubations with lipid extracts from lipolyzed VLDL or with purified palmitic acid in the absence of lipolysis. Complex formation was inhibited by addition of increasing amounts of albumin as free fatty acid acceptor, but could be detected at molar ratios of free fatty acids/albumin that occur in vivo. Composition analysis of LDL reisolated following incubation with VLDL and lipase under conditions favoring partial complex formation revealed enrichment in glycerides and depletion of cholesterol. We conclude that lipolysis products can promote the formation of stable complexes of LDL and VLDL, and that physical interactions of this nature may play a role in the transfer of lipids and apolipoproteins between lipoprotein particles.


Ultrasimple air-annealed pure graphene oxide film for high-performance supercapacitors.
Realizing both high gravimetric and volumetric specific capacitances (noted as CW and CV, respectively) is an essential prerequisite for the next-generation, high performance supercapacitors. However, the need of electronic/ionic transport for electrochemical reactions causes a "trade-off" between compacted density and capacitance of electrode, thereby impairing gravimetric or volumetric specific capacitances. Herein, we report a high-performance, film-based supercapacitor via a thermal reduction of graphene oxide (GO) in air. The reduced, layer-structured graphene film ensures high electrode density and high electron conductivity, while the hierarchical channels generated from reduction-induced gas releasing process offer sufficient ion transport pathways. Note that the resultant graphene film is employed directly as electrodes without using any additives (binders and conductive agents). As expected, the as-prepared electrodes perform particularly well in both CW (420F g-1) and CV (360F cm-3) at a current density of 0.5 A g-1. Even at an ultrahigh current density of 50 A g-1, CW and CV maintain in 220F g-1 and 189F cm-3, respectively. Furthermore, the corresponding symmetric two-electrode supercapacitor achieves both high gravimetric energy density of 54 W h kg-1 and high gravimetric power density of 1080 W kg-1, corresponding to volumetric energy density of 46 W h L-1 and volumetric power density of 917 W L-1.


Treatment of MSW landfill leachate by a thin gap annular UV/H2O2 photoreactor with multi-UV lamps.
The treatment of leachate from landfills is a major disposal problem for municipal solid waste. The leachate is generally recalcitrant to be treated according to complicated characteristics and high color intensity resulting further threat for environment and human health. In this work, the designed thin gap annular photoreactor with 4-UV lamps in UV/H2O2 process was proposed to decolor and remove chemical oxygen demand (COD) from the landfill leachate for solving this environmental problem. Meanwhile, the operating parameters such as UV dosage, hydrogen peroxide concentration and leachate strength were evaluated. The landfill leachate treated with the maximum dosage of 4-UV lamps and 232.7 mM of hydrogen peroxide concentration achieved 72 and 65% of color and COD removal efficiencies in 300 min. As for less concentrated leachate of 20% strength, 91% of color and 87% of COD were removed within only 120 min. From the experimental results, the UV/H2O2 process in this work was an effective pre-treatment or treatment technology for landfill leachate.


High resolution cryo-EM structures of TRPC5-Gαi3 complexes reveal direct activation of an ion channel by Gαi-GTP.
Transient receptor potential canonical 4 and 5 (TRPC4 and TRPC5) are Ca2+-permeable nonselective cation channels known to be activated by Gi/o proteins. Recently, Won et al. (Nat Commun. 2023, 14:2550) reported the cryo-EM structures of TRPC5 in complex with Gαi3. The G protein alpha subunit was found to directly bind to an ankyrin-like repeat domain in the periphery of the cytosolic portion of TRPC5 some 50 Å away from the membrane. This establishes the TRPC4/C5 ion channels as true effectors of Gα subunits, although the channel gating still depends on the coexistence of Ca2+ and phosphatidylinositol 4,5-bisphosphate.


[Gastric leiomyoblastoma. Description of a case with the cytological findings and review of the literature].
A case of gastric leiomyoblastoma observed in a 76 year old woman, with details of its cytological and histological diagnosis, is reported. Cytologically, the tumour showed spindle-shaped cells, either single or arranged in clusters and bundles and constituted of epithelial-like cells with moderately irregular and hyperchromatic nuclei. The macroscopic specimen showed an ulcerated mass measuring 3.5 x 2 x 2 cm. Histologically the neoplasm showed interlacing fascicles of spindle-shaped, pleomorphic and epithelioid cells, infiltrating the gastric smooth muscle tissue, but not extending beyond it. The main cyto-histological diagnosis and parameters predictive of benign and malignant behaviour in leiomyoblastoma are discussed.


XeCl laser action at medium fluences on biological tissues: fluorescence study and simulation with a chemical solution.
A rat heart, isolated and perfused, was irradiated with a XeCl excimer laser at 308 nm. The evolution of the fluorescence spectrum was measured. For an incident energy E greater than 4 kJ m-2 per pulse the fluorescence changed with time in a complex and spectrally non-uniform way. The proposed interpretation is that the radiation acts on the cellular respiratory chain. Buffered solutions of NADH, cytochrome c and FAD, which play a role in the respiratory chain, were irradiated in order to simulate the in vivo findings. The conclusion of this study is that XeCl radiation introduces a modification in the functioning of the respiratory chain: it accelerates electron transfer, but this quickly leads to an interruption of the respiratory chain.


Difficulties of healthcare workers encountered under cohort isolation in a psychiatric hospital during the COVID-19 pandemic: A qualitative study.
This study examined the experiences of healthcare workers who were quarantined within the psychiatric wards due to COVID-19 and analyzed those experiences with a consensual qualitative research method. Participants experienced (a) difficulties due to the specificity of a mental hospital, including a lack of protocols, noncompliance with quarantine guidelines among patients with severe mental illness, and a shortage of institutions capable of containing confirmed COVID-19 patients with severe mental illness. Furthermore, (b) difficulties related to isolation of the cohort itself included a workforce shortage, physical problems, fear of infection, limited facilities, guilt toward newly confirmed cases, exhaustion, and distress caused by separation from family. The participants also described (c) difficulties related to external factors, including administrative orders and the perceived stigma, and (d) positive experiences. Appropriate support is needed during the COVID-19 pandemic to reduce the difficulties among healthcare workers in psychiatric hospitals. This includes preparation for future scenarios, facilities, and workers in response to outbreaks of infection in psychiatric hospitals that cause unique risks and challenges among those workers.


Long Follow-Up of Radiosurgery for Brainstem Cavernoma.
There is a relative paucity of long-term follow-up of treatment of brainstem cavernous angiomas. This has led to uncertainty and a lack of consensus regarding optimum therapy, especially radiosurgery. Report of a single case with a 24-year follow-up. This patient was minimally symptomatic before her radiosurgery procedure. She developed an acute complication, from which she incompletely recovered. Two decades later she has become more symptomatic, with new deficits, and magnetic resonance imagings disclose progressive brainstem atrophy. Long-term follow-up of patients treated with radiosurgery is important.


Estrogen protects primary cortical neurons from glutamate toxicity.
The gonadal steroid estrogen has been shown to affect neuronal growth, differentiation and survival. We examined the ability of estrogen to protect primary cortical neurons from toxicity induced by the excitatory neurotransmitter glutamate. In these experiments, a 24-h pretreatment with 15 and 50 nM 17 beta-estradiol significantly reduced cellular lactate dehydrogenase (LDH) release from primary cortical neurons, indicating that neurons treated with 17 beta-estradiol were protected from a toxic glutamate exposure. Pretreatment with related steroids such as progesterone, dihydrotestosterone, dexamethasone or cholesterol did not significantly decrease LDH release. The anti-estrogen tamoxifen blocked the protective effects of 17 beta-estradiol suggesting that a classical steroid hormone receptor may be involved in the mechanism subserving estrogen neuroprotection during glutamate toxicity.


Dietary supplementation of Pseudoalteromonas piscicida 1UB and fructooligosaccharide enhance growth performance and protect the whiteleg shrimp (Litopenaeus vannamei) against WSSV and Vibrio harveyi coinfection.
P. piscicida 1Ub and FOS were evaluated for their potential synbiotic effects on growth, immunological responses, and disease resistance against white spot syndrome virus and V. harveyi coinfection, the major pathogen in whiteleg shrimp aquaculture. Four different supplemented diets were used to feed the experimental shrimp for 40 days: control (control, no probiotic, and prebiotic), probiotic (PRO, P. piscisida 1UB 108 CFU mL-1), prebiotic (PRE, FOS 0.5% w/w), and the synbiotic (SYN, PRO + PRE). Shrimp's body weight, weight gain, specific growth rate, feed conversion ratio, survival, digestive enzyme activity, and metabolism-related gene expression were all evaluated on day 40. After 40 days, shrimp were infected with WSSV as the primary infection and V. harveyi as the secondary infection 24 h later. Shrimp were then grown for seven days and fed with a control diet. Survival, total hemocyte count (THC), differential hemocyte, phenol-oxidase (PO), respiratory burst activity (RB), and immune-gene expression were all analyzed at 0, 3, and 7 days after infection. The results showed that the PRO, PRE, and SYN supplementation improves whiteleg shrimp growth performance, immune responses, and protection against WSSV and V. harveyi coinfection. The increased activity of digestive enzymes and metabolism-related genes correlates with higher growth performance. The increase in THC, PO, RB, and immune-related gene expression after coinfection was associated with a significant reduction in shrimp mortality. Our findings also suggest that supplementing with synbiotics improves the overall performance of whiteleg shrimp significantly more than probiotics or prebiotics only.


Bactericidal or bacteristatic effects of two sulphonamide plus trimethoprim preparations in human urine.
Rrine collections were made by ten volunteers taking cotrimoxazole and a sulphamoxole/trimethoprim combination on a cross-over basis. The latter was given in approximately half the dose of cotrimoxazole. Following collection of urine and its sterile filtration, the trimethoprim and sulphonamide concentrations were estimated. The urines were then inoculated with various species of Enterobacteriaceae whose minimum inhibitory concentrations had been previously determined. The viable counts in these urines were followed for 24 hours and from these the times to kill 90% of bacteria were calculated. These were very reproducible for any one experiment but showed no correlation with drug concentration, source of the urine or organism sensitivity, except for one organism which had high resistance to both sulphonamide and trimethoprim. When the organism was sensitive to at least trimethoprim a slow bactericidal effect was generally seen with either combination. We concluded that in this type of experiment the higher dosed combination showed no advantage contrary to a previous report, but in agreement with another. This brings into question the current dosage regime of cotrimoxazole when used to treat urinary tract infections in that its higher dosage over certain other sulphonamide/trimethoprim combinations appears to confer no advantage in our experiments.


A mutant EGF-receptor defective in ubiquitylation and endocytosis unveils a role for Grb2 in negative signaling.
Ligand-induced desensitization of the epidermal growth factor receptor (EGFR) is controlled by c-Cbl, a ubiquitin ligase that binds multiple signaling proteins, including the Grb2 adaptor. Consistent with a negative role for c-Cbl, here we report that defective Tyr1045 of EGFR, an inducible c-Cbl docking site, enhances the mitogenic response to EGF. Signaling potentiation is due to accelerated recycling of the mutant receptor and a concomitant defect in ligand-induced ubiquitylation and endocytosis of EGFR. Kinetic as well as morphological analyses of the internalization-defective mutant receptor imply that c-Cbl-mediated ubiquitylation sorts EGFR to endocytosis and to subsequent degradation in lysosomes. Unexpectedly, however, the mutant receptor displayed significant residual ligand-induced ubiquitylation, especially in the presence of an overexpressed c-Cbl. The underlying mechanism seems to involve recruitment of a Grb2 c-Cbl complex to Grb2-specific docking sites of EGFR, and concurrent acceleration of receptor ubiquitylation and desensitization. Thus, in addition to its well-characterized role in mediating positive signals, Grb2 can terminate signal transduction by accelerating c-Cbl-dependent sorting of active tyrosine kinases to destruction.


Acute vasculitis resulting in free flap failure: the importance of early recognition and options for management.
Unusual or unexpected medical causes for free flap failure do occur but are uncommon. We present a rare case of a fibula free flap failure due to an acute vasculitis which was undiagnosed until after the flap had failed. In addition to two successful flap salvages and intravenous heparin, an epoprostenol infusion was commenced but a third salvage was not successful. The vasculitis resulted in marked blood vessel wall thickening, and cutaneous manifestations which presented as late signs. High peri-nuclear anti nuclear cytoplasmic antibody (pANCA) and myeloperoxidase (MOP) titres were subsequently found and histology from several blood vessels showed marked inflammation throughout the wall. A diagnosis of microscopic polyangiitis was made and high dose steroids were subsequently commenced. Interestingly, he had vasculitis several years previously treated with oral steroids but had been discharged from the rheumatology clinic. This rare case illustrates the potential hazards of free flap surgery in the vasculitides and discusses the warning signs and various management options to reduce the likelihood of flap failure in these patients.


The Look AHEAD Trial: Implications for Lifestyle Intervention in Type 2 Diabetes Mellitus.
Given the array of adverse health consequences of obesity, including increased risk for type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD), the Look AHEAD trial (N=5145) was conducted to test the hypothesis that an intensive lifestyle intervention (ILI) for weight loss would achieve significantly greater reductions in CVD morbidity and mortality than a control condition of diabetes support and education (DSE) among participants with T2DM. A number of significant and long-term improvements were observed for ILI, including body weight, physical fitness and physical function, glucose control, quality-of-life (QoL), and healthcare costs. However, ILI did not significantly reduce CVD-related morbidity/mortality (i.e., CVD death, non-fatal MI, non-fatal stroke, hospitalized angina) after nearly 10 years of follow-up. There was a suggestion of heterogeneity of response based on the history of prior CVD at baseline (p=0.06). Despite the overall lack of CVD risk reduction, ILI remains important for care of patients with T2DM, particularly when accompanied by medication management. In particular, ILI may be an appealing option for patients wanting to minimize medication intensification. Also, ILI carries with it other potential benefits important to patients (e.g., improvements in physical functioning and QoL). Based on data from other trials, intensive medication management, such as tight glycemic control, is not without potential risks, which should be weighed in making treatment decisions. Future research is needed to determine if results observed in this trial would be replicated among younger patients, those without established T2DM, and/or those with no pre-existing CVD.


Depression and anxiety in unemployed men.
Psychiatric status and psychosocial variables were assessed in a group of 80 unemployed men. Symptoms of depression and anxiety were assessed using the Present State Examination and 'caseness' rated according to the Bedford College criteria. Among men who were normal at the time of job loss, 14% developed a 'case' disorder and a further 17% a 'borderline case' disorder over the first 6 months of unemployment. These rates are similar to those found in studies concerned with a wider range of severe life events. An increased risk of onset was associated with three factors: lack of an intimate relationship with a wife or girlfriend, trait shyness, and pre-existing economic difficulties.


"Self-Healing": A Novel and Integrated Multimodal Concept for the Management of Musculoskeletal Pain.
Musculoskeletal (MSK) conditions, particularly low back pain and osteoarthritis, are a leading cause of disability worldwide. The number of people with MSK conditions is set to increase over the coming decades highlighting the need for better tools for both patients and medical practitioners. A recent paper by McSwan, Gudin and co-authors introduces the concept of the innate ability of the body to "self-heal" through five body networks, whilst being optimized by integrative multi-modal medicine and natural remedies ranging from the physical to psychological, that are starting to be incorporated into clinical management and treatment guidelines. "Self-Healing" is a new concept for MSK pain management and reinforces the potential for integrating multi-modal medicine into current care through open dialogue between patients and healthcare providers.


Hypertension in urban slums of southern India: Burden, awareness, health seeking, control and risk factor profile.
Hypertension is the leading risk factor for global disease burden. Inequalities in health among urban poor and non-poor is a matter of concern. The current study was done to estimate the prevalence of hypertension and to describe the health seeking and risk factor profile of people with hypertension in the urban slums of Kochi, Kerala, India. Blood pressure of 5980 adults from 20 randomly selected slums were measured by door to door survey by trained nurses as a part of baseline assessment for a cluster randomised controlled trial. Prevalence of hypertension was found to be 34.8% (95% CI 33.5-34.9). Among those with hypertension, 66.9% were aware of their hypertensive status, of which 75.8% were initiated on treatment for hypertension. Proportion of hypertensive in the population who had their blood pressure under control was 24.5%. Among hypertensive, 53% were obese, 25.1% had diabetes mellitus, 14% had history of hospitalisation for high blood pressure. Of them, 60.3% had a per capita salt consumption above 8 g/day and 47.5% of them reported sitting for more than 8 h on a usual day. Mean monthly out of pocket expenditure for treatment of hypertension was $9(Median $8, IQR $16). One in three adults in urban slums of Kochi had hypertension. High rates of obesity, salt intake, physical inactivity prevails among the people with hypertension. Awareness, treatment initiation and control rate of hypertension are lower in urban slums as compared to non-slum urban areas. Slums require additional attention to ensure equitable and universal access to hypertension control.


[Inhibitory effects of AA-2414, a thromboxane (Tx) A2 receptor antagonist, on U-46619-, prostaglandin (PG) D2- and 9 alpha, 11 beta PGF2-induced contractions of guinea pig tracheas and isolated human bronchi].
The effects of a novel TXA2 receptor antagonist, AA-2414 [(+-)-7-(3,5,6-trimethyl-1,4-benzoquinone-2-yl)-7-phenyl-heptanoic acid], on U-46619-, PGD2- and 9 alpha, 11 beta-PGF2 alpha-induced contractions of isolated guinea pig tracheas and human bronchi were investigated. AA-2414 competitively inhibited the contractile responses of both human and guinea pig preparations induced by U-46619 with similar pA2 values (7.7 and 7.6, respectively). In addition, the compound also inhibited the contractions of both preparations caused by PGD2 and 9 alpha, 11 beta-PGF2 alpha, the IC50 values of which were 1.2 x 10(-7) and 1.8 x 10(-7) M in guinea pig tracheas and 2.8 x 10(-8) and 8.5 x 10(-8) M in human bronchi. These results suggest that AA-2414 may be a therapeutically useful drug for bronchial asthma.


Recurrent lentigo maligna melanoma commingling the tumour nests of a basal cell carcinoma.
There are various types and combinations of coexisting cutaneous neoplasms which have been documented in the past but are uncommon. In this report we describe a case of basal cell carcinoma (BCC) colonised by recurrent lentigo maligna melanoma. A review of the literature has established the coexistence of lentigo maligna and BCC in six cases. The unusual combination of melanoma and BCC poses a therapeutic and prognostic dilemma. BCC is known to have a favourable outcome whereas melanoma tends to behave in a more aggressive manner leading to a less favourable outcome. There are conflicting views as to whether these lesions should be treated as BCC's or lentigo maligna melanoma. Our case appears to be unique, in that it was a recurrent lentigo maligna melanoma which was colonising the BCC. We treated our patient with wide local excision and full thickness skin graft and will continue to observe him on an outpatient basis. There needs to be long term follow up of a larger number of patients for us to truly appreciate the biological significance of parasitism of BCC by lentigo maligna melanoma.


Renal, vesical, and prostatic calculi associated with ochronosis.
A case report of a patient with ochronosis and simultaneously occurring renal, vesical, and prostatic calculi is presented. Literature review suggests an increased incidence of urinary calculi in this syndrome, yet stone composition in such cases is not remarkable.


A catalogue of 1,167 genomes from the human gut archaeome.
The human gut microbiome plays an important role in health, but its archaeal diversity remains largely unexplored. In the present study, we report the analysis of 1,167 nonredundant archaeal genomes (608 high-quality genomes) recovered from human gastrointestinal tract, sampled across 24 countries and rural and urban populations. We identified previously undescribed taxa including 3 genera, 15 species and 52 strains. Based on distinct genomic features, we justify the split of the Methanobrevibacter smithii clade into two separate species, with one represented by the previously undescribed 'Candidatus Methanobrevibacter intestini'. Patterns derived from 28,581 protein clusters showed significant associations with sociodemographic characteristics such as age groups and lifestyle. We additionally show that archaea are characterized by specific genomic and functional adaptations to the host and carry a complex virome. Our work expands our current understanding of the human archaeome and provides a large genome catalogue for future analyses to decipher its impact on human physiology.


LncRNA LINC00968 accelerates the proliferation and fibrosis of diabetic nephropathy by epigenetically repressing p21 via recruiting EZH2.
Emerging evidence have indicated the vital roles of long noncoding RNAs (lncRNAs) in the pathophysiological process of diabetic nephropathy. However, the deepgoing mechanism that lncRNAs regulate the diabetic nephropathy pathogenesis is still ambiguous. In present study, we found that lncRNA LINC00968 expression was high-expressed in the diabetic db/db mouse tissue and high-glucose induced mesangial cells. Functional experiments indicated that LINC00968 silencing by siRNAs significantly inhibited the proliferation and cycle progression, and decreased the extracellular matrix (ECM) proteins (fibronectin, collagen IV) expression in the high glucose induced of mesangial cells. RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) assay revealed that LINC00968 recruit EZH2 to the promoter of p21 to inhibit its expression. In summary, our results support the conclusion that lncRNA LINC00968 accelerates the proliferation and fibrosis of mesangial cells by epigenetically repressing p21 via recruiting EZH2, providing a novel insight for the diabetic nephropathy pathogenesis.


Chiroptical-responsive nanoprobe for the optosensing of chiral amino acids.
A supersensitive chiroptical-responsive system of enantioselectively recognizing L- and D-tryptophan (Trp) based on ( +)-diacetyl-L-tartaric anhydride-functionalized 1,3,5-triformylphloroglucinol (DTA-functionalized Tp) was constructed for the first time. With a high fluorescence quantum yield of 15.2% and fluorescence lifetime of 57.6 μs, DTA-functionalized Tp as both fluorescent and chiral recognition nanoprobe was used for the discrimination of L- and D-Trp with excitation/emission maxima at 330/490 nm within 3 min. The linear range of the fluorescence sensing was 0.002-0.15 μg mL-1, and the detection limit achieved 1.4 ng mL-1. Furthermore, a smartphone was employed as a detector and processor to couple with the chiroptical-responsive nanoprobe for establishing a novel and visual integration system for rapid and real-time detection of chiral amino acids with a detection limit of 13 ng mL-1. The spiked recoveries of L-Trp in two commercially available functional beverages ranged from 86.00 to 118.33% in fluorescence and smartphone-based sensing system. Based on the excellent chiroptical-responsive effects, high stability, and biocompatibility, the chiroptical-responsive nanoprobe was successfully applied to visual optosensing and fluorescence imaging in response to L- and D-Trp in HeLa cells. This discrimination methodology with high sensitivity and enantioselectively shows great potential for in-site visually monitoring chiral amino acids in real food samples and tracking physiological processes.


Radioprotective effect of a protein free parathyroid extract.
The radioprotective effect of a bovine protein-free parathyroid extract was studied in rats, being administered orally after irradiation. A significant increase in survival was found after treatment compared to conrols. It is assumed that the extract contains a new, probably as yet unknown bioactive agent responsible for the radioprotection.


Retrospective Case Control Study: Clinical and Computer Tomographic Fusion and Subsidence Evaluation for Single Level Uniportal Endoscopic Posterolateral Approach Transforaminal Lumbar Interbody Fusion Versus Microscopic Minimally Invasive Transforaminal Interbody Fusion.
Retrospective comparative study. Assessment of difference in clinical and computer tomographic outcomes between the 2 cohorts. Computer tomographic evaluation by Bridwell's grade, Kim's stage, Kim's subsidence grade and clinical evaluation by VAS, ODI and McNab's criteria on both cohorts. 33 levels of Endo-TLIF and 22 levels of TLIF were included, with a mean follow up of 14.3 (10-24) and 22.9 (13-30) months respectively. Both Endo-TLIF and TLIF achieved significant improvement of pain and ODI at post-operative 4 week, 3 months and at final follow up with VAS 4.39 ± 0.92, 5.27 ± 1.16 and 5.73 ± 1.21in Endo-TLIF and 4.55 ± 1.16, 5.05 ± 1.11 and 5.50 ± 1.20 in TLIF respectively and ODI at post-operative 1 week, 3 months and final follow up were 43.15 ± 6.57, 49.27 ± 8.24 and 51.73 ± 9.09 in Endo-TLIF and 41.73 ± 7.98, 46.18± 8.46 and 49.09 ± 8.98 in TLIF respectively, P < 0.05. Compared to TLIF, Endo-TLIF achieved better VAS with 0.727 ± 0.235 at 3 months and 0.727 ± 0.252 at final follow up and better ODI with 3.88 ± 1.50 at 3months and 3.42 ± 1.63 at final follow up, P < 0.05. At 6 months radiological evaluation comparison of the Endo-TLIF and TLIF showed significant with more favorable fusion rate in Endo-TLIF of -0.61 ± 0.12 at 6 months and -0.49 ± 0.12 at 1 year in Bridwell's grading and 0.70 ± 0.15 at 6 months and 0.56 ± 0.14 at 1 year in Kim's stage.There is less subsidence of 0.606 ± 0.18 at 6 months and -0.561 ± 0.20 at 1 year of Kim's subsidence grade, P < 0.05. Application of single level uniportal endoscopic posterolateral lumbar interbody fusion achieved better clinical outcomes and fusion rate with less subsidence than microscopic minimally invasive transforaminal lumbar interbody fusion in mid-term evaluation for our cohorts of patients.


Factors influencing discharge location following high lesion spinal cord injury rehabilitation in British Columbia, Canada.
Retrospective chart review. To identify and describe factors that influence discharge location -- extended care unit (nursing home) or other (private home, group home, or acute care) -- following rehabilitation for individuals with a new high lesion spinal cord injury (SCI) (C1-C4) in British Columbia, Canada. GF Strong Rehabilitation Centre, Vancouver, British Columbia, Canada. Eligible clients were adults admitted to the GF Strong Rehabilitation Centre Spinal Cord Program between 1994 and 2003, with a new C1-4 lesion (traumatic or nontraumatic), and an ASIA score of A-C at time of discharge. Medical charts of 52 individuals were reviewed and data regarding individual characteristics, health-related characteristics, personal context, hospitalization factors, health resources, and other contextual factors were extracted. In total, 40% of clients were discharged to extended care units post rehabilitation. Seven variables were associated at a univariate level: age, employment at the time of injury, pre-existing medical conditions, social support, preinjury living situation, and insurance (worker's compensation or motor vehicle) or private funding for equipment. Four variables were associated at the multivariate level: age, preinjury living situation, and insurance or private funding for equipment. A range of individual, health-related, family and social policy variables influence discharge location following rehabilitation for high lesion SCI in British Columbia. The unique combination of variables presented by each individual should be considered by the rehabilitation team in the discharge planning process.


Use of stored serum from Uganda for development and evaluation of a human immunodeficiency virus type 1 testing algorithm involving multiple rapid immunoassays.
We report the development and evaluation of a human immunodeficiency virus type 1 testing algorithm consisting of three rapid antibody detection tests. Stored serum samples from Uganda were utilized with a final algorithm sensitivity of 100% and a specificity of 98.9% (95% confidence interval, 98.6% to 99.3%).


SH3P2, an SH3 domain-containing protein that interacts with both Pib and AvrPib, suppresses effector-triggered, Pib-mediated immunity in rice.
Plants usually keep resistance (R) proteins in a static state under normal conditions to avoid autoimmunity and save energy for growth, but R proteins can be rapidly activated upon perceiving pathogen invasion. Pib, the first cloned blast disease R gene in rice, encoding a nucleotide-binding leucine-rich repeat (NLR) protein, mediates resistance to the blast fungal (Magnaporthe oryzae) isolates carrying the avirulence gene AvrPib. However, the molecular mechanisms about how Pib recognizes AvrPib and how it is inactivated and activated remain largely unclear. In this study, through map-based cloning and CRISPR-Cas9 gene editing, we proved that Pib contributes to the blast disease resistance of rice cultivar Yunyin (YY). Furthermore, an SH3 domain-containing protein, SH3P2, was found to associate with Pib mainly at clathrin-coated vesicles in rice cells, via direct binding with the coiled-coil (CC) domain of Pib. Interestingly, overexpression of SH3P2 in YY compromised Pib-mediated resistance to M. oryzae isolates carrying AvrPib and Pib-AvrPib recognition-induced cell death. SH3P2 competitively inhibits the self-association of the Pib CC domain in vitro, suggesting that binding of SH3P2 with Pib undermines its homodimerization. Moreover, SH3P2 can also interact with AvrPib and displays higher affinity to AvrPib than to Pib, which leads to dissociation of SH3P2 from Pib in the presence of AvrPib. Taken together, our results suggest that SH3P2 functions as a "protector" to keep Pib in a static state by direct interaction during normal growth but could be triggered off by the invasion of AvrPib-carrying M. oryzae isolates. Our study reveals a new mechanism about how an NLR protein is inactivated under normal conditions but is activated upon pathogen infection.


The wavelength dependence of 8-methoxypsoralen photosensitization of radiation-enchanced reactivation in a mammalian cell-virus system.
The combined effect of 8-methoxypsoralen (8-MOP) and ultraviolet (UV) radiation on the ability of an irradiated mammalian cell (CV-1) to reactivate UV-irradiated mammalian virus (Herpes simplex) was tested. Prior treatment of cells with 8-MOP was found to increase Radiation-Enhanced Reactivation (RER) at one wavelength (297 nm) in the far ultraviolet but not at others (240-289 nm). This same treatment induced RER in the near UV (302-370 nm) and the visible region (380-400 nm). An action spectrum for the photo-sensitized induction of this cellular parameter was obtained. This action spectrum is consistent with the absorption spectrum for 8-MOP and the theory that damage to DNA is, at least in part, responsible for Radiation-Enhanced Reactivation.


Identification of the novel HLA-B*15:257 allele by polymerase chain reaction sequence-based typing in a Chinese individual.
HLA-B*15:257 has one nucleotide change in exon 2 at position 232C>G from B*15:01:01:01.


Kinetics of aggregation of UV-irradiated glyceraldehyde-3-phosphate dehydrogenase from rabbit skeletal muscle. Effect of agents possessing chaperone-like activity.
An aggregation test system based on the aggregation of UV-irradiated glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from rabbit skeletal muscle has been proposed. On the basis of the measurements of the enzyme activity and differential scanning calorimetry data a conclusion has been made that UV radiation results in formation of damaged protein molecules with lower thermostability. It was shown that the order of aggregation rate for UV-irradiated GAPDH with respect to the protein was close to 2. This means that such a test system allows detecting the effect of various agents exclusively on the stage of aggregation of unfolded protein molecules. The influence of α-crystallin and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) on aggregation of UV-irradiated GAPDH was studied. Despite the fact that HP-β-CD accelerates thermal aggregation of non-irradiated GAPDH, in the case of aggregation of UV-irradiated GAPDH HP-β-CD reveals a purely protective effect.


Development of a rabbit model of Wiskott-Aldrich syndrome.
The Wiskott-Aldrich syndrome (WAS) is a severe recessive X-linked immunodeficiency resulting from loss-of-function mutations in the WAS gene. Mouse is the only mammalian model used for investigation of WAS pathogenesis. However, the mouse model does not accurately recapitulate WAS clinical phenotypes, thus, limiting its application in WAS clinical research. Herein, we report the generation of WAS knockout (KO) rabbits via embryo co-injection of Cas9 mRNA and a pair of sgRNAs targeting exons 2 and 7. WAS KO rabbits exhibited many symptoms similar to those of WAS patients, including thrombocytopenia, bleeding tendency, infections, and reduced numbers of T cell in the spleen and peripheral blood. The WAS KO rabbit model provides a new valuable tool for preclinical trials of WAS treatment.


The radiographic and surgical evaluation of meniscal dysfunction of the temporomandibular joint.
A retrospective study of 106 patients who underwent temporomandibular joint surgery for meniscal dysfunction was conducted. The patients were evaluated by tomography and arthrography of the temporomandibular joint and abnormalities of the hard and soft tissue structures were determined by these investigations and compared directly with the findings at surgical examination. Tomography had a high degree of correlation with bony pathology as did arthrography with meniscal displacement. The arthrogram also frequently revealed the presence of meniscal scarring associated with the head of condyle in long-standing cases, but gave an incidence of 3% false/positive findings of a perforation of the meniscus.


Improvement with disodium cromoglycate of neutrophil phagocytosis and respiratory burst activity in a patient with hyperimmunoglobulin E syndrome.
We report a case of hyperimmunoglobulin E syndrome (HIE) complicated by neutrophil deficiency which was successfully treated with oral administration of disodium cromoglycate. A 48-year-old Japanese man with HIE developed Streptococcus pneumoniae meningitis. Laboratory tests after the meningitis revealed persistent neutropenia (300-800/mm3) and defects of phagocytosis and bacterial killing by neutrophils. Administration of disodium cromoglycate was started, and neutrophil counts gradually increased to 1200-1600/mm3. The impaired neutrophil activities returned to normal. The patient improved clinically; during the 2-year treatment, he had only two brief episodes of the common cold. Disodium cromoglycate may have potential clinical use in the treatment of cases of HIE even with neutrophil deficiency.


Flowering phenology, floral display and reproductive success in dioecious, Aralia nudicaulis L. (Araliaceae).
Aralia nudicaulis L. is a dioecious, perennial, herbaceous plant that is commonly found in the understory vegetation throughout the boreal forest of North America. Female remets have fewer flowers per inflorescence, initiate flowering earlier, and reach peak flowering before male ramets. The consequences of the asynchrony in flowering between the sexes on pollination and seed set were examined during a two-year study. In both years there was significant variation in seed set associated with the flowering times of individual female ramets. In 1983, seed production was highest in the middle of the flowering season. In 1984, seed production was greatest in the later stages of flowering. Variation in seed set was not attributed to lack of pollination in 1983. In 1984, pollination limited seed set per flower during peak flowering. However, seed production never reached the potential five seeds per flower, suggesting that resource limitation was the most important factor affecting fecundity in both years. The asynchronous pattern of flowering is suggested to be the result of the different inflorescence sizes between the sexes.


Quadriceps and Hamstrings Strength Reference Values for Athletes With and Without Anterior Cruciate Ligament Reconstruction Who Play Popular Pivoting Sports, Including Soccer, Basketball, and Handball: A Scoping Review.
To synthesize and present reference values for quadriceps and hamstrings strength tests in healthy athletes who play pivoting sports and in athletes with anterior cruciate ligament reconstruction (ACLR) who play pivoting sports. Scoping review. We searched PubMed, the Cochrane Library, MEDLINE, Embase, and Web of Science up to January 26, 2021. We included reference values in 2 different categories: (1) quadriceps and hamstrings strength test outcomes in healthy pivoting-sport athletes, and (2) quadriceps and hamstrings strength test outcomes in pivoting-sport athletes with ACLR at a specific time point during rehabilitation. We performed a qualitative synthesis for reference values from isokinetic (at 60°/s, 180°/s, and 300°/s) and isometric quadriceps and hamstrings strength tests. We summarized the data for type of sport, sex, sport participation level, and age group. Of the 42 included studies, 26 reported reference values from healthy soccer players, 4 from healthy basketball players, 4 from healthy handball players, and 11 from other healthy pivoting-sport athletes. The limb symmetry index dominant/nondominant limb (LSI-D/ND) ranged from 98% to 114% for healthy athletes. Six studies reported reference values in pivoting-sport athletes with ACLR at a specific time point during rehabilitation. After 7 months, strength values for athletes with ACLR were comparable to those of healthy pivoting-sport athletes. This scoping review summarizes quadriceps and hamstrings strength reference values for athletes who play the most common pivoting sports, including soccer, basketball, and handball. J Orthop Sports Phys Ther 2022;52(3):142-155. Epub 31 Dec 2021. doi:10.2519/jospt.2022.10693.


High-Quality Surgery for Gallbladder Carcinoma: Rare, Associated with Disparity, and Not Substitutable by Chemotherapy.
Oncologic surgery for T1b-T3 gallbladder carcinoma (GBC) consists of gallbladder fossa resection or bisegmentectomy IVb/V with negative margins and portal/retropancreatic lymphadenectomy. Frequency of high quality oncologic surgery, factors associated with its use, and the ability of chemotherapy to rescue low-quality surgery (LQS) remain unknown. The NCDB was queried for patients diagnosed with stage I-III (T1b-T3) GBC undergoing curative-intent surgery from 2004 to 2016. These patients were divided into two groups based on receiving high quality surgery (HQS) or not; HQS was defined as cholecystectomy with partial hepatectomy, lymph node harvest ≥ 6, and negative margins. Logistic regression and Kaplan-Meier survival analyses were performed. A total of 3796 patients met inclusion criteria; only 364 (9.6%) met HQS criteria, and 3432 (90.4%) did not achieve HQS and were deemed low-quality surgery (LQS). HQS was associated with improved median overall survival (55.1 vs. 25.5 months, P < .001). Adjuvant chemotherapy (AC) was not able to rescue LQS with poorer survival compared to HQS without AC (27.9 vs 55.1 months, P < .001). Factors associated with HQS included private insurance (OR 1.809, P < .001), higher income (OR 1.380, P = .038), urban/rural residence (vs metropolitan) (OR 1.641, P = .001), higher education (OR 1.342, P = .031), Medicaid expansion states (OR 1.405, P = .005), stage 3 GBC (OR 1.642, P = .020), and reresection (OR 2.685, P < .001). Factors associated with LQS included older age (OR 0.974, P < .001), comorbidities (OR 0.701, P = .004), and laparoscopic approach (0.579, P < .001). Facility type incrementally improved HQS rate (integrated cancer network vs. comprehensive community, 9.8% vs. 6.1%, OR 1.694, P = .003; academic/research center vs. integrated cancer network, 14.9% vs. 9.8%, OR 1.599, P = .003). While HQS for GBC strongly improves survival, it is infrequently practiced. The newly identified factors that improve survival for GBC, such as centralization, open approach, and insurance coverage, are modifiable and, therefore, should be considered to achieve optimal outcomes.


Non-toxigenic Vibrio cholerae bacteraemia: case report and review of the literature.
Vibrio cholerae is a serious public health problem worldwide, but in the UK, V. cholerae infections are rare. Here, we report a case of V. cholerae bacteraemia in an elderly patient. To our knowledge, this is the first non-travel-related V cholerae bacteraemia in the UK.


Is There a Role for Cerebral Ultrasonography in Near-Term/Term Neonates Following Assisted Vaginal Delivery? A Prospective, Single-Center Study.
To evaluate the role of cerebral ultrasonography studies (CUSS) in detecting intracerebral and cranial pathologies (hemorrhages, ischemia, skull fractures) in near-term and term neonates following assisted vaginal delivery. Prospective single-center study (11/2017-11/2018) at the University Children's Hospital of Saarland, Homburg, Germany including newborns with a gestational age ≥ 36 weeks born by assisted vaginal delivery. In all newborns, a standardized CUSS was performed within the first three days of life prior to discharge. 200 neonates (43.0 % female, 57.0 % male; gestational age 39.6 ± 1.3 weeks) were included in this study (birth weight 3345.6 ± 450.6 g, body length 51.7 ± 2.5 cm, head circumference 35.0 ± 1.5 cm). 67 (33.5 %) neonates had minor external injuries of the scalp. 5 children showed clinical neurologic abnormalities: 4 (2.0 %) seizures and 1 facial palsy (0.5 %). In 34 (17.0 %) patients, minor incidental intracranial abnormalities unrelated to mode of delivery were detected on CUSS. No intracerebral, cranial pathologies or skull fractures were seen on routine CUSS. Routine CUSS in newborns after assisted vaginal delivery did not yield clinically relevant results in our cohort. Clinical observation and selective CUSS in symptomatic newborns might be more efficient than routine CUSS.


Acute psycosis in systemic lupus erythematosus.
Psychiatric manifestations are common in systemic lupus erythematosus (SLE) and often represent a challenging diagnostic and therapeutic problem, mainly because the uncertainties of the pathogenic mechanisms. We report a case of acute psychosis occurring in a female with SLE due to the stress of having a severe disease, rather than to SLE per se.


Dietary immature Citrus unshiu alleviates UVB- induced photoaging by suppressing degradation of basement membrane in hairless mice.
Ultraviolet (UV) irradiation induces physiological and morphological skin damage, resulting in skin dryness, wrinkle formation, and loss of elasticity. The basement membrane (BM) has been shown to play crucial roles in binding epidermis to dermis tightly, regulating cell differentiation and proliferation, and signaling protein production. Dietary flavonoids have been revealed to improve the damage caused by UV exposure. Immature Citrus unshiu is known to contain high concentrations of flavonoids such as hesperidin and narirutin. In this study, the effects of immature Citrus unshiu powder (ICP) on photoaged skin were demonstrated using UVB irradiated hairless mice. Oral administration of ICP improved loss of skin hydration and increase of transepidermal water loss. The histological analyses of hairless mice dorsal skin revealed that oral administration of ICP improved UVB-induced overgrowth of epidermal cell, suppressed epidermal cell mortality and BM destruction. Therefore, the administration of ICP could improve photoaging by protecting the tissues around BM.


The dawn of aspirin free strategy after short term dual antiplatelet for percutaneous coronary intervention: meta-analysis of randomized controlled trials.
There is still a debate about the safety and efficacy of an aspirin free strategy after percutaneous coronary intervention (PCI). Hence, we performed a meta-analysis comparing aspirin free strategy to dual antiplatlets therapy (DAPT). Randomized trials (RCTs) comparing aspirin free strategy to DAPT in patients who received PCI were included. The primary outcome of interest was bleeding, defined per the Bleeding Academic Research Consortium (BARC). Secondary outcomes included major adverse cardiovascular and cerebrovascular events (MACE); defined as all-cause mortality, myocardial infarction or stroke, the individual component of MACE and stent thrombosis. A total of 4 RCTs with 29,089 patients were included. There was significant reduction in BARC 2,3 or 5 bleeding events in patients who were treated with aspirin free strategy versus DAPT (HR 0.61, 95% CI 0.39-, p = 0.03, I2 = 89%). Moreover, although there was a trend of reduced major bleeding (BARC 3 or 5) outcomes in the aspirin free strategy group compared to the DAPT group, this did not achieve statistical significance (HR 0.63, 95% CI 0.37-1.06, p = 0.08, I2 = 795). Additionally, there was no difference between the aspirin free strategy and DAPT in term of MACE (HR 0.92, 95% CI 0.82-1.03, p = 0.13, I2 = 0%), all-cause mortality (HR 0.89, 95% CI 0.77-1.04, p = 0.15, I2 = 0%), MI (HR 0.89, 95% CI 0.74-1.08, p = 0.24, I2 = 0%), stroke (HR 1.13, 95% CI 0.65-1.99, p = 0.66, I2 = 60%) or stent thrombosis (HR 0.1.01, 95% CI 0.83-1.22, p = 0.93, I2 = 0%). Aspirin free strategy is as effective as DAPT in reducing MACE with better safety profile in term of bleeding.


Microbial interaction ofAspergillus parasiticus andBacillus subtilis withalternaria alternata. production of alternariol, alternariol monomethylether and tenuazonic acid on sunflower seeds.
Production of alternariol, alternariol mono-methylether and tenuazonic acid byAlternaría alternata was studied in competition withAspergillus parasiticus andBacillus subtilis on irradiated sunflower seeds at 0.90 aw.In cultures co-inoculated withAlternaría alternata andAspergillus parasiticus alternariol production decreased by 64%. Similar results were observed in cultures co-inoculated withAlternaría alternata andBacillus subtilis.


The Alcohol Treatment Outcome Measure (ATOM): a new clinical tool for standardising outcome measurement for alcohol treatment.
Whilst many instruments have been developed for screening and treatment outcome evaluation studies in the alcohol and other drug treatment (AOD) sector, very few are suitable for routine, ongoing use by clinicians. The aim of the current study was to assess the psychometric properties of the Alcohol Treatment Outcome Measure (ATOM). The ATOM was designed to measure the key outcomes of alcohol treatment whilst remaining a brief and easy to use clinical tool. Participants (N=134) with a concern for their alcohol use were recruited from AOD treatment agencies and interviewed on two occasions one week apart. Results indicate that the ATOM has overall good to excellent test-retest and inter-rater reliability; and satisfactory concurrent validity and internal reliability. The instrument also demonstrated the ability to measure change in client functioning over time. Results suggest that the ATOM can be used successfully and confidently within alcohol treatment services.


Prevalence and significance of ventriculoatrial conduction.
Because retrograde atrioventricular conduction may predispose to pacemaker-induced tachycardia when DDD pacing is employed, we assessed ventriculo-atrial conduction in 117 patients undergoing electrophysiologic studies. Ventriculo-atrial conduction was present in 40% with a mean (+/- sem) conduction time of 205 +/- 12 ms. The maximum VA conduction time following minimum extrastimulus intervals averaged 258 +/- 14 ms. Antegrade AV nodal properties predicted VA conduction in only 67% by using stepwise discriminant analysis. Only the PR interval, AH interval, and AV nodal effective refractory periods were helpful in predicting ventriculo-atrial conduction. Although ventriculo-atrial conduction time increased on most antiarrhythmic drugs, it was infrequently eliminated.


Eating together as a social network intervention for people with mild intellectual disabilities: a theory-based evaluation.
People with mild intellectual disabilities (MID) generally live independently among the wider community. This can result in social exclusion and feelings of loneliness. Therefore, social work organizations aim to socially include people with MID through organizing activities in neighbourhoods that should lead to enlarged networks and increased societal participation. The "Communal Table" is such a, group-orientated, intervention that organizes monthly dinners in Amsterdam, the Netherlands. Because little is known about the effectiveness of interventions aiming to bring about social inclusion for people with MID we explored which types of participants were reached and whether and how the intervention brought about the intended outcomes. We performed a theory-based evaluation, using participatory observations and qualitative interviews (n = 19). The Communal Table attracted a diverse and loyal group of participants. We distinguished four types of participants-lonely participants, activist participants, satisfied participants and calculating participants-whose pre-existing networks played a significant role in their individual needs for support and the outcomes of the intervention. Outcomes reported included experiences of conviviality and warmth, temporary relief of underlying problems and an overall positive opinion about the intervention, but network enlargement or increased societal participation were not reported. Our findings suggest that social network interventions for people with MID should be tailored to participants' pre-existing networks and related individual needs to be successful.


The Orosomucoid 1 protein is involved in the vitamin D - mediated macrophage de-activation process.
Orosomucoid 1 (ORM1), also named Alpha 1 acid glycoprotein A (AGP-A), is an abundant plasma protein characterized by anti-inflammatory and immune-modulating properties. The present study was designed to identify a possible correlation between ORM1 and Vitamin D3 (1,25(OH)2D3), a hormone exerting a widespread effect on cell proliferation, differentiation and regulation of the immune system. In particular, the data described here indicated that ORM1 is a 1,25(OH)2D3 primary response gene, characterized by the presence of a VDRE element inside the 1kb sequence of its proximal promoter region. This finding was demonstrated with gene expression studies, Chromatin Immunoprecipitation and luciferase transactivation experiments and confirmed by VDR full length and dominant negative over-expression. In addition, several experiments carried out in human normal monocytes demonstrated that the 1,25(OH)2D3--VDR--ORM1 pathway plays a functional role inside the macrophage de-activation process and that ORM1 may be considered as a signaling molecule involved in the maintenance of tissue homeostasis and remodeling.


Politicized Demography and Biomedical Authority in Post-Soviet Russia.
We explore obstetrician-gynecologists' (ob-gyns') shifting involvement in late Soviet and post-Soviet reproductive politics and track broader political-economic dynamics of the profession's ambivalent relations with state demographic discourses. Soviet ob-gyns largely distanced themselves from explicitly pronatalist agendas. Post-soviet national politics of 'population renewal' and the neoliberalization of health care have significantly restructured ob-gyns' orientations. To assert their authority and gain economic footing, ob-gyns have highlighted their contributions to the state's demographic agendas. The post-Soviet context illustrates how understanding the medicalization of population problems requires examining the political-economic relations between physicians and the state - dynamics that can transform ideologies and medical practices.


The glaucoma suspect: differentiation of the future glaucoma eye from the non-glaucomatous suspect eye. 2. Visual field decay.
Visual-field areas to a I2e stimulus were measured planimetrically using an X-Y digitizer and a computer program. Sampling of normal subjects and patients suspected of having glaucoma was done at two points in time. Calculations of eye-wall stress were done using ultrasonic data and intra-ocular pressure (IOP) measurements from patient records. For those suspected of having glaucoma who developed chronic open-angle glaucoma (COAG), the time of transition was the second point in time. The visual field area was regressed against patient age at the two points in time. No difference in the regression slopes was found for the normal subjects and unchanged patients. The patients who did develop glaucoma were significantly different. The mean annual rate of visual-field change (rate of decay) was calculated and found to be 28.5 mm2/year for the normals, 153.5 mm2/year for the suspects, and 376.4 mm2/year for those patients who developed glaucoma. The rate of visual-field decay only correlated with patient age (P = 0.03) and eye-wall stress (P less than 0.01) in the patients who developed glaucoma.


Plasma cortisol responses to stress in lactating and nonlactating female rhesus macaques.
Lactating female rats without their pups exhibit lower HPA responsiveness to stress than nonlactating females. However, responsiveness to stress is similar when lactating females are tested with their pups and the stressor involves a potential threat to the offspring. This study constitutes the first comparison of stress responsiveness in lactating and nonlactating female nonhuman primates. Subjects were 53 multiparous female free-ranging rhesus macaques. Approximately half of the females were lactating and half were nonpregnant/nonlactating. Blood samples were obtained after capture and after overnight housing in an individual cage. Lactating females were tested with their infants. Lactating females had significantly higher plasma cortisol levels than nonlactating females on both days. Having or not having an infant was also a better predictor of plasma cortisol levels among all females than their age, dominance rank, group of origin, time of day at which the sample was obtained, and time elapsed since beginning of the sampling procedure or since anesthesia. Plasma cortisol levels of lactating females were not significantly correlated with post-partum stage or with the cortisol levels of their infants. Capture, handling, and individual housing in a cage are powerful psychological stressors for free-ranging primates. We suggest that the higher plasma cortisol levels exhibited by lactating females reflect greater responsiveness to stress associated with perception of risks to infants. Hyporesponsiveness to stress may not be a general characteristic of lactation in all mammalian species, but a short-term effect of infant suckling that is most apparent with stressors unrelated to the offspring.


De-implementation of Axillary Dissection in Women Undergoing Mastectomy for Breast Cancer.
Completion axillary lymph node dissection (cALND) was standard treatment for breast cancer with positive sentinel lymph nodes (SLNs) until 2011, when data from the Z11 and AMAROS trials challenged its survival benefit in early stage breast cancer. We assessed the contribution of patient, tumor, and facility factors on cALND use in patients undergoing mastectomy and SLN biopsy. Using the National Cancer Database, patients diagnosed from 2012 to 2017 who underwent upfront mastectomy and SLN biopsy with at least one positive SLN were included. A multivariable mixed effects logistic regression model was used to determine the effect of patient, tumor, and facility variables on cALND use. Reference effect measures (REM) were used to compare the contribution of general contextual effects (GCE) to variation in cALND use. From 2012 to 2017, the overall use of cALND decreased from 81.3% to 68.0%. Overall, younger patients, larger tumors, higher grade tumors, and tumors with lymphovascular invasion were more likely to undergo cALND. Facility variables, including higher surgical volume and facility location in the Midwest, were associated with increased use of cALND. However, REM results showed that the contribution of GCE to the variation in cALND use exceeded that of the measured patient, tumor, facility, and time variables. There was a decrease in cALND use during the study period. However, cALND was frequently performed in women after mastectomy found to have a positive SLN. There is high variability in cALND use, mainly driven by interfacility practice variation rather than specific high-risk patient and/or tumor characteristics.


Selected polymorphisms of DNA repair genes and risk of pancreatic cancer.
Genetic variants of DNA repair genes may contribute to pancreatic carcinogenesis. O(6)-methylguanine-DNA methyltransferase (MGMT) is the major protein that removes alkylating DNA adducts, and apurinic/apyrimidinic endonuclease 1 (APE1) and X-ray repair cross-complementing group 1 (XRCC1) play important roles in the base excision repair pathway. We investigated the association between polymorphisms of MGMT (Leu(84)Phe and Ile(143)Val), APE1 (Asp(148)Glu), and XRCC1 (Arg(194)Trp and Arg(399)Gln) and risk of pancreatic cancer in a case-control study. Exposure information from 384 patients with primary pancreatic ductal adenocarcinoma and 357 cancer-free healthy controls were collected and genomic DNAs were genotyped for five markers. Controls were frequency matched to patients by age at enrollment (+/-5 years), gender, and race. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) by using unconditional logistic regression models. There was no significant main effect or interaction with smoking of these genetic variants on the risk of pancreatic cancer. However, the XRCC1(194) polymorphism had a significant interaction with the APE1(148) (p=0.005) or MGMT(84) polymorphism (p=0.02) in modifying the risk of pancreatic cancer. This study suggests that polymorphisms of genes involved in the repair of alkylating DNA adduct and DNA base damage may play a role in modulating the risk of pancreatic cancer. Larger studies are required to validate these preliminary findings. The mechanism of the combined genotype effects remains to be elucidated.


Feasibility of a novel remote daily monitoring system for age-related macular degeneration using mobile handheld devices: results of a pilot study.
This pilot study evaluated the feasibility of the Health Management Tool (HMT), a novel computing system using mobile handheld devices, to remotely monitor retinal visual function daily in patients with neovascular age-related macular degeneration treated with ranibizumab. Patients with neovascular age-related macular degeneration in at least 1 eye (newly diagnosed or successfully treated < 1 year) and eligible for ranibizumab therapy were enrolled in this 16-week, prospective, open-label, single-arm study. Patients performed a shape discrimination hyperacuity test (myVisionTrack [mVT]) daily on the HMT device (iPhone 3GS) remotely and at all clinic visits. Data entered into HMT devices were collected in the HMT database, which also sent reminders for patients to take mVT. Among 160 patients from 24 U.S. centers enrolled in the study (103 [64%] ≥ 75 years of age), 84.7% on average complied with daily mVT testing and ≈ 98.9% complied with at least weekly mVT testing. The HMT database successfully uploaded more than 17,000 mVT assessment values and sent more than 9,000 reminders. Elderly patients with neovascular age-related macular degeneration were willing and able to comply with daily self-testing of retinal visual function using mobile handheld devices in this novel system of remote vision monitoring.


Prediction of in-plane organ deformation during free-breathing radiotherapy via discriminative spatial transformer networks.
External beam radiotherapy is a commonly used treatment option for patients with cancer in the thoracic and abdominal regions. However, respiratory motion constitutes a major limitation during the intervention. It may stray the pre-defined target and trajectories determined during planning from the actual anatomy. We propose a novel framework to predict the in-plane organ motion. We introduce a recurrent encoder-decoder architecture which leverages feature representations at multiple scales. It simultaneously learns to map dense deformations between consecutive images from a given input sequence and to extrapolate them through time. Subsequently, several cascade-arranged spatial transformers use the predicted deformation fields to generate a future image sequence. We propose the use of a composite loss function which minimizes the difference between ground-truth and predicted images while maintaining smooth deformations. Our model is trained end-to-end in an unsupervised manner, thus it does not require additional information beyond image data. Moreover, no pre-processing steps such as segmentation or registration are needed. We report results on 85 different cases (healthy subjects and patients) belonging to multiples datasets across different imaging modalities. Experiments were aimed at investigating the importance of the proposed multi-scale architecture design and the effect of increasing the number of predicted frames on the overall accuracy of the model. The proposed model was able to predict vessel positions in the next temporal image with a median accuracy of 0.45 (0.55) mm, 0.45 (0.74) mm and 0.28 (0.58) mm in MRI, US and CT datasets, respectively. The obtained results show the strong potential of the model by achieving accurate matching between the predicted and target images on several imaging modalities.


Effects of novel microimplant-assisted rapid palatal expanders manufactured by 3-dimensional printing technology: A finite element study.
The expansion effects of several new microimplant-assisted rapid palatal expanders (MARPEs) manufactured by 3-dimensional printing technology were evaluated by finite element analysis (FEA). The aim was to identify a novel MARPE suitable for treating maxillary transverse deficiency. The finite element model was established using MIMICS software (version 19.0; Materialise, Leuven, Belgium). First, the appropriate microimplant insertion characteristics were identified via FEA, and several MARPEs with the above insertion patterns were manufactured by 3-dimensional printing technology. Then, the stress distribution and displacement prediction of the 4 MARPEs and hyrax expander (model E) were evaluated via FEA: bone-borne (model A), bone-tooth-borne (model B), bone-mucous-borne (model C), bone-tooth-mucous-borne (model D). Monocortical microimplants perpendicular to the cortical bone on the coronal plane resulted in better expansion effects. Compared with a conventional hyrax expander, the orthopedic expansion of each of the 4 MARPEs was far larger, the parallelism was greater, and the posterior teeth tipping rate was lower. Among them, the expansion effects of models C and D were the best; the von Mises peak values on the surfaces of the microimplants were smaller than those of models A and B. This study may demonstrate that the 4 MARPEs obtained more advantageous orthopedic expansion effects than a hyrax expander. Models C and D obtained better biomechanical effects and had better primary stability. Overall, model D is the recommended expander for treating maxillary transverse deficiency because its structure acts like an implant guide and is beneficial for the accurate insertion of the microimplant.


GABA attenuates the neurotoxic effects of ethanol in neuron-enriched cultures from 8-day-old chick embryo cerebral hemispheres.
Neuron-enriched cultures were prepared from 8-day-old chick embryo cerebral hemispheres and exposed to ethanol (50 mM), GABA (10(-5) M) and ethanol (50 mM) + GABA (10(-5) M) from day 4 to 8 in culture. At day 8, control, ethanol, GABA and ethanol + GABA-treated cultures were examined morphologically and biochemically. Choline acetyltransferase (ChAT) and glutamic acid decarboxylase (GAD) activities were used as markers for cholinergic and GABAergic neuronal phenotypic expression, respectively. Control cultures showed more numerous and large neuronal aggregates as well as prominent neuritic bundles. Moreover, cultures treated with GABA depicted even more numerous neuronal aggregates with interconnecting neurites as compared to control. In contrast, ethanol-treated cultures exhibited smaller neuronal aggregates with less prominent neuritic bundles than control. However, cultures treated concomitantly with ethanol + GABA exhibited numerous and larger aggregates than cultures treated with ethanol alone. Neuritic bundles which were highly reduced in ethanol-treated cultures became prominent in the presence of GABA. As previously reported, ethanol alone enhanced ChAT and reduced GAD activities. GABA given alone enhanced the expression of both neuronal phenotypes. When GABA was given concomitantly with ethanol the decline in GAD and the rise in ChAT observed in ethanol-treated cultures was restored by GABA to almost control levels. Thus, ethanol-induced alterations in morphology and neuronal phenotypes were counteracted by the neurontrophic effect of GABA.


Is it possible to use low-dose deep learning reconstruction for the detection of liver metastases on CT routinely?
To compare the image quality and hepatic metastasis detection of low-dose deep learning image reconstruction (DLIR) with full-dose filtered back projection (FBP)/iterative reconstruction (IR). A contrast-detail phantom consisting of low-contrast objects was scanned at five CT dose index levels (10, 6, 3, 2, and 1 mGy). A total of 154 participants with 305 hepatic lesions who underwent abdominal CT were enrolled in a prospective non-inferiority trial with a three-arm design based on phantom results. Data sets with full dosage (13.6 mGy) and low dosages (9.5, 6.8, or 4.1 mGy) were acquired from two consecutive portal venous acquisitions, respectively. All images were reconstructed with FBP (reference), IR (control), and DLIR (test). Eleven readers evaluated phantom data sets for object detectability using a two-alternative forced-choice approach. Non-inferiority analyses were performed to interpret the differences in image quality and metastasis detection of low-dose DLIR relative to full-dose FBP/IR. The phantom experiment showed the dose reduction potential from DLIR was up to 57% based on the reference FBP dose index. Radiation decreases of 30% and 50% resulted in non-inferior image quality and hepatic metastasis detection with DLIR compared to full-dose FBP/IR. Radiation reduction of 70% by DLIR performed inferiorly in detecting small metastases (< 1 cm) compared to full-dose FBP (difference: -0.112; 95% confidence interval [CI]: -0.178 to 0.047) and full-dose IR (difference: -0.123; 95% CI: -0.182 to 0.053) (p < 0.001). DLIR enables a 50% dose reduction for detecting low-contrast hepatic metastases while maintaining comparable image quality to full-dose FBP and IR. • Non-inferiority study showed that deep learning image reconstruction (DLIR) can reduce the dose to oncological patients with low-contrast lesions without compromising the diagnostic information. • Radiation dose levels for DLIR can be reduced to 50% of full-dose FBP and IR for detecting low-contrast hepatic metastases, while maintaining comparable image quality. • The reduction of radiation by 70% by DLIR is clinically acceptable but insufficient for detecting small low-contrast hepatic metastases (< 1 cm).


Activation of innate antiviral immune response via double-stranded RNA-dependent RLR receptor-mediated necroptosis.
Viruses induce double-stranded RNA (dsRNA) in the host cells. The mammalian system has developed dsRNA-dependent recognition receptors such as RLRs that recognize the long stretches of dsRNA as PAMPs to activate interferon-mediated antiviral pathways and apoptosis in severe infection. Here we report an efficient antiviral immune response through dsRNA-dependent RLR receptor-mediated necroptosis against infections from different classes of viruses. We demonstrated that virus-infected A549 cells were efficiently killed in the presence of a chimeric RLR receptor, dsCARE. It measurably suppressed the interferon antiviral pathway but promoted IL-1β production. Canonical cell death analysis by morphologic assessment, phosphatidylserine exposure, caspase cleavage and chemical inhibition excluded the involvement of apoptosis and consistently suggested RLR receptor-mediated necroptosis as the underlying mechanism of infected cell death. The necroptotic pathway was augmented by the formation of RIP1-RIP3 necrosome, recruitment of MLKL protein and the activation of cathepsin D. Contributing roles of RIP1 and RIP3 were confirmed by gene knockdown. Furthermore, the necroptosis inhibitor necrostatin-1 but not the pan-caspase inhibitor zVAD impeded dsCARE-dependent infected cell death. Our data provides compelling evidence that the chimeric RLR receptor shifts the common interferon antiviral responses of infected cells to necroptosis and leads to rapid death of the virus-infected cells. This mechanism could be targeted as an efficient antiviral strategy.


Post-tetanic count and profound neuromuscular blockade with atracurium infusion in paediatric patients.
In 38 paediatric surgical patients given atracurium by infusion, the degree of neuromuscular blockade was monitored using the post-tetanic twitch response. This was assessed by counting the number of visible responses when single twitch stimulation was applied at 1 Hz for 30 s after a 5-s tetanic stimulation at 50 Hz. A post-tetanic count of less than 10 correlated with a single twitch height of less than 5% of control, and ensured adequate paralysis. Once the count was greater than 15, the blockade could be antagonized readily.


An assessment of the evidence for the role of ribonucleoprotein particles in the maturation of eukaryote mRNA.
This article has sought to draw together, on the one hand, what is known of mRNA processing and its control and, on the other hand, what is known of the structure and validity of hnRNP and snRNP particles. At the same time, it has attempted to synthesize these two themes into a critical assessment of the evidence which suggests that the particles are intimately involved in processing. It cannot be said that the case is proven. The evidence is compelling but circumstantial. The last few years have seen the development of the first in vitro splicing systems (Weingartner and Keller, 1981; Goldenberg and Raskus, 1981; Kole and Weissman, 1982), the isolation of monoclonal antibodies to defined snRNP (Lerner et al., 1981a; Billings et al., 1982) and hnRNP proteins (Hugle et al., 1982), and the ability to use artificial lipid vesicles to transfer antisera (Lenk et al., 1982) and radioactive snRNA (Gross and Cetron, 1982) into cells. It is to be hoped that further refinements of these and other techniques will allow us to solve this, one of the major outstanding problems of molecular biology.


Common ground: hospitals, physicians and outpatient centers.
Physician-owned ambulatory surgery centers are projected to keep growing. For at least one hospital, it's a sign to start partnering and stop competing.


Changes in serum C-reactive protein during complicated and uncomplicated measles virus infections.
Serum C-reactive protein levels become elevated coincident with the onset of the rash in patients with measles. Serum C-reactive protein elevations are prolonged in measles complicated by pneumonia and may show a second elevation in measles complicated by encephalitis.


Effect of Jiajian Guishen Formula on the senescence-associated heterochromatic foci in mouse ovaria after induction of premature ovarian aging by the endocrine-disrupting agent 4-vinylcyclohexene diepoxide.
Jiajian Guishen Formula (JJGSF), which is a prescription of Traditional Chinese Medicine (TCM), has been reported to be useful in the treatment of premature ovarian insufficiency (POI). To investigate the therapeutic effects of JJGSF on the treatment of POI induced by 4-vinylcyclohexene diep-oxide (VCD), an endocrine-disrupting chemical (EDC), and to elucidate the potential mechanism. Female 8-week-old ICR mice (N = 72) were randomized into six groups, containing the Model group, Control group, three JJGSF groups, and Progynova group which was served as a positive control. After model establishment by VCD, the Progynova group were given a daily intragastric administration of Progynova, and the three JJGSF groups (high dose group, medium dose group and low dose group) received a daily intragastric administration of JJGSF at doses of 9, 4.5 and 2.25 g/kg for four weeks. The general growth of the mice was observed and the estrous cycles were examined. The serum hormone concentrations were measured by enzyme-linked immunosorbent assay (ELISA). To explore the potential mechanism of effect, the protein expressions of H3K9me3, HP1, and HMGA1/HMGA2 related to senescence-associated heterochromatic foci (SAHF), were determined by Immunofluorescence and Western blot analysis, respectively. After treating with JJGSF, the estrous cycles were improved significantly. The level of estrogen (E2) and anti-müllerian hormone (AMH) was increased and the ratio of follicle-stimulating hormone (FSH) to luteinizing hormone (LH) in serum was decreased significantly. Furthermore, a significant down-regulation of HMGA1/HMGA2 on protein level, a reduction distribution of HP1 and H3K9me3 in ovarian, and a lower fraction of SAHF-positive cells were observed after the administration with JJGSF, additionally effects showed a positive correlation with dosages. JJGSF could treat POI by the mechanism of inhibiting SAHF.


Adaptation of Staphylococcus aureus to the cystic fibrosis lung.
Staphylococcus aureus colonizes the lungs of cystic fibrosis (CF) patients and despite treatment with antibiotics results in recurrent and relapsing infections. With increasing duration of the infection, the bacterial population is exposed more and more to changing selective pressures exerted by the host immune system, to frequent therapeutic interventions, and to interference with other microorganisms. S. aureus has evolved a variety of strategies to adapt to these challenges: Recombination and mutation provide the population with a preselected heterogeneity, resulting in an inheritable shift of phenotypic traits. This includes the emergence of isolates with mutations in metabolic (e.g. small-colony variants) and regulatory (e.g. agr mutants) genes. Additionally, phages become mobilized with a higher frequency during infection, raising the propensity for recombination. On the other hand, S. aureus can also adapt to the CF lung using regulatory mechanisms which are not well understood in this context. The quorum-sensing system agr is not activated during lung infection in CF, which is consistent with a proposed biofilm mode of growth in the lungs and also with the observation that in CF patients the organism usually remains localized in the lungs without systemic manifestation. Altogether, adaptive processes result in the generation of a heterogeneous S. aureus population in the CF lung which is highly protected against antibiotic therapy, expressing factors necessary for persistence rather than virulence.


Attitudes of Turkish university employees and their relatives towards whole body and organ donation.
Dissection of human anatomic specimens still keeps its importance in medical curriculum. Experiences of medical students in the anatomy laboratory and the time they spent there makes them feel as doctors at the beginning of their education and helps them to get used to the notion of death. Unfortunately, the number of human body donors available for medical research and education as well as organ transplantation is limited. Obtaining human anatomic specimens continues being a great problem especially in middle-east countries. Religious factors, socioeconomic status, education, marital status or age are probably the main factors those effect body donations. The aim of the present study is to evaluate the attitudes of Turkish university employees and their relatives towards whole body donation and organ donation. A total of 780 questionnaires taken from the participants were evaluated. All the participants were academic and administrative staff from four different universities based in Ankara, Eskişehir, İstanbul and Adana and their relatives. Participants were between the ages of 18-85. All the subjects were provided a questionnaire composed of 38 questions. 26.2% of the individuals declared that they could donate their body for medical education while 73.8% of them did not. In contrast, 69.1% of the participants were willing for being organ donors. Of the ones who had accepted to donate their organs, 64.5% refused to donate their bodies. The results of this study indicate that not only whole body donation, but also organ donation continue being a problem in Turkey.


A comparative study of antipyrine pharmacokinetics in saliva and plasma using a colourimetric method of antipyrine analysis.
1. Half-life, apparent volume of distribution and metabolic clearance rate for antipyrine elimination were reliably estimated from either plasma or saliva samples. 2. Pharmacokinetic analysis of antipyrine from saliva utilizing a simple and sensitive colourimetric technique provided a convenient method for assessing the activity of hepatic microsomal drug-metabolizing enzymes.


Review: systemic toxicity associated with the intravenous administration of colchicine--guidelines for use.
Published experiences with severe toxicity with intravenous colchicine have been reviewed. All reported cases reflect inappropriate use of the drug. Therapeutic rules for colchicine have been derived from this information: (1) Single intravenous doses should not exceed 2-3 mg, and cumulative total doses for an attack should not be more than 4-5 mg. (2) Patients should receive no more colchicine by any route for 7 days. (3) Colchicine doses must be reduced in the presence of renal or hepatic disease, and in the older patient with apparently normal renal function. (4) Intravenous colchicine doses should be half the size of oral ones. (5) Absolute contraindications to intravenous colchicine therapy for acute gout include combined renal and hepatic disease, creatinine clearances below 10 cc/min, and extrahepatic biliary obstruction.


Application of three-dimensional micro-optical components formed by lithography, electroforming, and plastic molding.
Micro-optics is usually associated with planar waveguides or integrated optical circuits. In this case the propagation of light is restricted to one or two dimensions, and the three-dimensional nature of light propagation is disregarded. We present a method of fabricating three-dimensional micro-optical components by the so-called LIGA process, a lithography, electroforming, and plastic molding process in which poly(methyl methacrylate) is structured by high-energy synchrotron radiation. We demonstrate an experimental system of image formation that uses microprisms and microlenses for a threedimensional microintegration of optical components.


Platform for investigating continuum manipulator behavior in orthopedics.
The use of robotic continuum manipulators has been proposed to facilitate less-invasive orthopedic surgical procedures. While tools and strategies have been developed, critical challenges such as system control and intra-operative guidance are under-addressed. Simulation tools can help solve these challenges, but several gaps limit their utility for orthopedic surgical systems, particularly those with continuum manipulators. Herein, a simulation platform which addresses these gaps is presented as a tool to better understand and solve challenges for minimally invasive orthopedic procedures. An open-source surgical simulation software package was developed in which a continuum manipulator can interact with any volume model such as to drill bone volumes segmented from a 3D computed tomography (CT) image. Paired simulated X-ray images of the scene can also be generated. As compared to previous works, tool-anatomy interactions use a physics-based approach which leads to more stable behavior and wider procedure applicability. A new method for representing low-level volumetric drilling behavior is also introduced to capture material variability within bone as well as patient-specific properties from a CT. Similar interaction between a continuum manipulator and phantom bone was also demonstrated between a simulated manipulator and volumetric obstacle models. High-level material- and tool-driven behavior was shown to emerge directly from the improved low-level interactions, rather than by need of manual programming. This platform is a promising tool for developing and investigating control algorithms for tasks such as curved drilling. The generation of simulated X-ray images that correspond to the scene is useful for developing and validating image guidance models. The improvements to volumetric drilling offer users the ability to better tune behavior for specific tools and procedures and enable research to improve surgical simulation model fidelity. This platform will be used to develop and test control algorithms for image-guided curved drilling procedures in the femur.


Absence of contralateral suppression of transiently evoked otoacoustic emissions in fibromyalgia syndrome.
To assess contralateral suppression of transiently evoked otoacoustic emissions in patients with fibromyalgia syndrome and normal hearing. Twenty-four female patients with fibromyalgia syndrome and 24 healthy female controls with normal hearing were assessed using pure tone audiometry and transiently evoked otoacoustic emissions. All patients with fibromyalgia syndrome and all controls had normal hearing on pure tone audiometry. In the patients with fibromyalgia syndrome, the mean transiently evoked otoacoustic emission amplitude was 15.5 +/- 4.8 dB. The mean transiently evoked otoacoustic emission amplitudes after contralateral suppression was 15.5 +/- 4.9 dB. There was no statistically significant difference between the transiently evoked otoacoustic emission amplitudes measured before and after contralateral suppression (p > 0.05). In the controls, the mean transiently evoked otoacoustic emission amplitude was 12 +/- 5 dB. The mean transiently evoked otoacoustic emission amplitudes after contralateral suppression was 11 +/- 4.7 dB. There was a statistically significant decrease in transiently evoked otoacoustic emission amplitudes after contralateral suppression (p < 0.01). The mechanisms related to contralateral suppression of transiently evoked otoacoustic emissions seem dysfunctional in fibromyalgia syndrome. This dysfunction may be at the brain stem level, where the medial superior olivary complex is located, or at the synapses of medial superior olivary complex fibres with the outer hair cells in the cochlea. Demonstration of lack of contralateral suppression of transiently evoked otoacoustic emissions can be used as a diagnostic tool in patients with fibromyalgia syndrome.