The QPLEX™ Plus Assay Kit for the Early Clinical Diagnosis of Alzheimer's Disease.
We recently developed a multiplex diagnostic kit, QPLEX™ Alz plus assay kit, which captures amyloid-β1-40, galectin-3 binding protein, angiotensin-converting enzyme, and periostin simultaneously using microliters of peripheral blood and utilizes an optimized algorithm for screening Alzheimer's disease (AD) by correlating with cerebral amyloid deposition. Owing to the demand for early AD detection, we investigate the potential of our kit for the early clinical diagnosis of AD. A total of 1395 participants were recruited, and their blood samples were analyzed with the QPLEX™ kit. The average of QPLEX™ algorithm values in each group increased gradually in the order of the clinical progression continuum of AD: cognitively normal (0.382 ± 0.150), subjective cognitive decline (0.452 ± 0.130), mild cognitive impairment (0.484 ± 0.129), and AD (0.513 ± 0.136). The algorithm values between each group showed statistically significant differences among groups divided by Mini-Mental State Examination and Clinical Dementia Rating. The QPLEX™ algorithm values could be used to distinguish the clinical continuum of AD or cognitive function. Because blood-based diagnosis is more accessible, convenient, and cost- and time-effective than cerebral spinal fluid or positron emission tomography imaging-based diagnosis, the QPLEX™ kit can potentially be used for health checkups and the early clinical diagnosis of AD.


Advances of droplet-based microfluidics in drug discovery.
Drug discovery through a large number of candidates with nearly unlimited possibilities is laborious, time-consuming, and incurs massive costs. It thus calls for fast and robust methods that allow for handling small amounts of reagents, automation, and high-throughput analysis. In this regard, droplet-based microfluidic platforms provide several unique advantages. Highly monodispersed droplets can be generated in a high frequency and serve as microcontainers with just a few femtoliter to nanoliter volume. Furthermore, each of them can be manipulated to initiate specific reactions in parallel. Consequently, droplet microfluidics is emerging as a useful tool for drug discovery and development. The authors provide a brief overview of the latest developments of droplet-based microfluidic techniques for drug discovery and emphasize their applications at different stages, covering target selection, drug candidate identification, and preclinical research. Droplet-based microfluidics holds great potential in drug discovery due to its capability of reaction miniaturization and high-throughput analysis. However, its commercial applications are still at an early stage as the experiments are mostly implemented utilizing custom-built instruments in laboratory environments. Thus, joint efforts from scientists and engineers with multidisciplinary backgrounds are required to optimize the standardization and stability of droplet-based microfluidic platforms.


Medicinal Plants in the Treatment of Colitis: Evidence from Preclinical Studies.
Ulcerative colitis is a chronic inflammatory condition whose treatment includes aminosalicylates, corticosteroids, and immunomodulators. Medicinal plants seem to be an important alternative treatment for this condition. They have been the subject of a great number of studies in recent years. This study was conducted to systematically review the medicinal plants tested in experimental models of ulcerative colitis. We conducted a systematic literature search through specialized databases (PUBMED, SCOPUS, EMBASE, MEDLINE, LILACS, SCIELO, and SCISEARCH) and selected articles published between January 2000 and June 21, 2016 by using "medicinal plants" and "ulcerative colitis" as key words. Sixty-eight studies were included, and the families Asteraceae and Lamiaceae presented the largest number of studies, but plants from several other families were cited; many of them have shown good results in experimental animals. However, only a few species (such as Andrographis paniculata and Punica granatum) have undergone clinical tests against ulcerative colitis, and the observation that many preclinical studies reviewed are purely descriptive has certainly contributed to this fact. Chemical constituents (mainly flavonoids and terpenes) seem to play a role in the effects of the plants. Thus, the data herein reviewed reinforce the potential of medicinal plants as a source of alternative approaches to the treatment of ulcerative colitis.


Cellular defense of the avian respiratory system: protection against Escherichia coli airsacculitis by Pasteurella multocida-activated respiratory phagocytes.
The concept of nonspecific cellular defense of the respiratory system of poultry against respiratory pathogens by "preventive activation" of avian respiratory phagocytes (ARPs) was tested in an in vivo protection trial. Chickens were stimulated intratracheally by Pasteurella multocida Choloral vaccine strain. Seven hours later, these and mock-inoculated control chickens were challenged with pathogenic Escherichia coli via the air-sac route. Stimulated chickens had a 25-fold-elevated number of ARPs compared with mock-inoculated control chickens. The proportion of active phagocytes and the phagocytic capacity of these cells was higher in the ARP populations of stimulated chickens than in the ARP populations of control chickens. In vivo protection against E. coli air-sac infection was demonstrated by reduction of morbidity and mortality rates, diminished weight loss, and lower scores of gross and histopathological lesions of P. multocida-stimulated chickens compared with mock-inoculated controls.


Progressive dysphasic dementia with localized cerebral atrophy: report of an autopsy.
A 64-year-old Japanese woman showed an initially aphasic disturbance followed by complete mutism, progressive dementia, parkinsonism and muscular atrophy. Autopsy revealed localized cortical atrophy confined to the pars triangularis, pars opercularis of the inferior frontal gyrus, supramarginal and angular gyri of the inferior parietal lobe, precuneus and posterior half of the middle and inferior temporal gyrus predominantly on the left hemisphere. The right cerebellar hemisphere showed crossed cerebellar atrophy with shrinkage of the right middle cerebellar peduncle. In the atrophied cerebral areas there were diffuse outfall of neuronal cells in all cortical layers and remaining neurons generally showed simple atrophy, and there were a few swollen neurons. Gliosis of the subcortical white matter was confined to the affected gyri and GFAP positive astrocytes were observed in the 1st, 2nd, 5th and 6th layers of the cortex. In addition, the degenerative changes of the substantia nigra, gliosis of the amygdaloid complex and inferior olivary nucleus were bilaterally observed. The distribution and characteristics of the cortical and white matter degeneration are different from those of Pick's disease, and it is likely that this case belongs to a group of so-called degenerative dysphasic dementias.


Oscillatory amplification of stochastic resonance in excitable systems.
We study systems which combine both oscillatory and excitable properties, and hence intrinsically possess two internal frequencies, responsible for standard spiking and for small amplitude oscillatory limit cycles (Canard orbits). We show that in such a system the effect of stochastic resonance can be amplified by application of an additional high-frequency signal, which is in resonance with the oscillatory frequency. It is important that for this amplification one needs much lower noise intensities as for conventional stochastic resonance in excitable systems.


Field evaluation of female attractants for monitoring Ceratitis capitata (Diptera: Tephritidae) under a range of climatic conditions and population levels in Western Australia.
Field trials were conducted in Western Australia to compare captures of the Mediterranean fruit fly, Ceratitis capitata (Wiedemann), in a standard male-targeted trap (Lynfield trap baited with Capilure) with a synthetic, female-targeted attractant marketed as BioLure. BioLure was also compared with other fenale attractants (orange ammonia, liquid protein bait) and tested in plastic McPhail, Tephri, and Lynfield traps. The possibility of using one trap to monitor female and male C. capitata populations was also tested by combining BioLure in a trap with the male attractant, Capilure. The results of these experiments show that BioLure outperformed the female-targeted system currently used for monitoring female C. capitala (liquid protein in MePhail trap). More male C. capitata were caught in the standard male-targeted trap, but more females were caught in traps baited with BioLure irrespective of trap type, climate, host tree, or population level. Combined lure traps caught equivalent total numbers of C. capitata to the standard male-targeted trap, but fewer females were captured. Tephri traps caught more flies than McPhail traps, but McPhail traps caught equivalent proportions of females. We compared the performance in commercial orchards of the standard male-targeted trap with a female-targeted trap (McPhail with BioLure). We found that the male trap detected C. capitata more often, caught more flies, triggered the economic threshold more often (66% of the time) and was more cost effective. The male-targeted trap is recommended for use on commercial orchards if cost is limiting. However, using both male and female-targeted traps increases the chance of detecting flies and triggering the economic threshold level. The synthetic female attractant is recommended for replacement of protein hydrolysate lures and may be used in either Tephri or McPhail traps.


[The mind -- body problem].
In this paper I present, in the first place, two of the main problems in the philosophy of mind: 1) the problem of the criteria of the mental, and 2) the problem of the relationship between the mental and the physical. In the last part, I mention two problems highly discussed nowadays which, in my view, will produce the most important advance in the knowledge of our minds in the next decades: the problem of consciousness and its neural basis, and the problem of the origin and development of a theory of mind.


Food insecurity and socio-demographic characteristics in two UK ethnic groups: an analysis of women in the Born in Bradford cohort.
The use of foodbanks has risen sharply in the UK; however, the epidemiology of UK food insecurity is undeveloped. This study contributes to the field by analysing socio-demographic risk factors for food insecurity in a female, ethnically diverse population. Data from the Born in Bradford (BiB) cohort were matched with data on food insecurity from the nested BiB1000 study (N = 1280). Logistic regression was used to model food insecurity in relation to ethnicity and socio-demographic factors. Food insecurity, reported by 13.98% of the sample, was more likely among White British than Pakistani women (crude Odds Ratio (OR) 1.94, 95% CI: 1.37; 2.74, adjusted OR 2.37, 95% CI: 1.57; 3.59). In fully adjusted analyses, food insecurity was associated with a range of socio-economic measures, particularly the receipt of mean-tested benefits (adjusted OR 2.11, 95% CI: 1.41; 3.15) and perception of financial insecurity (adjusted OR 8.91, 95% CI: 4.14; 19.16 for finding it difficult/very difficult compared to living comfortably). The finding that food insecurity prevalence may be higher than previously thought and that food insecurity is highly associated with socio-economic status, notably benefit receipt, is a cause for concern necessitating an urgent policy response.


Pyoderma gangrenosum and pregnancy: an example of abnormal inflammation and challenging treatment.
Pyoderma gangrenosum (PG) is a neutrophil-predominant inflammatory disease that initially presents as a sterile pustule and may progress to ulcerations. Its root cause is unknown, but the presentation is commonly associated with systemic inflammatory conditions such as inflammatory bowel disease, arthritis and haematological abnormalities. On the other hand, pregnant women show a progressive neutrophilia during gestation, which culminates in a major inflammatory event to help drive labour. Although uncommonly, PG has been associated with pregnancy, which provides an additional link to systemic inflammation as an underlying cause of PG. We reviewed documented presentations of PG in gravid and post-partum patients, and have speculated on the possible pathogenesis based on their clinical presentations. Also, we summarize the reported treatments and their outcomes in these patients.


Cavi-Care: a forgotten dressing?
The 'ideal wound dressing' obviously depends on the requirements of the wound in question. Nevertheless, dressing characteristics that commonly facilitate an optimum healing environment are: The ability to adapt to wound position, size, depth and shape Being of high comfort; Being soft, with a moist wound interface Providing an effective barrier against exogenous microbes Being of competitive cost Having the ability.


Cerebral Venous Sinus Thrombosis Secondary to Idiopathic Hypertrophic Cranial Pachymeningitis: Case Report and Review of Literature.
Idiopathic hypertrophic cranial pachymeningitis (IHCP) is a rare fibrosing inflammatory process involving the dura mater. Currently, there is no consensus on the treatments for IHCP, and the usefulness of immunosuppressive agents as a first-line option remains controversial. Cerebral venous sinus occlusion (CVSO) and cerebral venous sinus thrombosis (CVST) secondary to IHCP, which may cause progressive intracranial hypertension and venous obstructive parenchymal lesions, make the diagnosis and treatment of IHCP more complicated. We present a case of IHCP. We also review previous cases of IHCP with secondary CVSO/CVST and then summarize the clinical characteristics of these patients. A 52-year-old female patient with IHCP developed secondary CVST. She had a severe headache with a hyperintense lesion on computed tomography, which was considered as subarachnoid hemorrhage. Lumbar tapping with a cerebrospinal fluid test, in addition to gadolinium contrast-enhanced magnetic resonance imaging, suggested IHCP. Secondary CVST was identified by digital subtraction angiography and magnetic resonance venography. Fatal intracranial hypertension with severe neurologic deficits occurred, despite mannitol, furosemide, and corticoid therapy. After administration of intravenous pulse cyclophosphamide, she obtained complete remission. We experienced a patient with CVST secondary to IHCP, who was successfully treated with cyclophosphamide pulse therapy. Because IHCP with secondary venous obstruction has various differential diagnoses, venography is necessary to avoid misdiagnosis. The use of immunosuppressive agents may be promising but needs further verification.


Isolation and properties of porcine lecithin:cholesterol acyltransferase.
Lecithin: cholesterol acyltransferase (LCAT, phosphatidylcholine: sterol O-acyltransferase, EC 220.127.116.11) was purified approximately 20 000-fold from pig plasma by ultracentrifugation, phenyl-Sepharose and hydroxyapatite chromatography. Purified LCAT had an apparent relative molecular mass of 69 000 +/- 2000. By isoelectrofocusing it separated into five or six bands with pI values ranging from pH 4.9 to 5.2. The amino acid composition was similar to that of the human enzyme. An antibody against pig LCAT was prepared in goat. The antibody reacted against pig LCAT and gave a reaction of partial identity with human LCAT. Incubation of pig plasma or purified enzyme with the antibody virtually inhibited LCAT activity. The same amount of antibody inactivated only 62% of the LCAT activity in human serum. Pig and human LCAT were activated to the same extent by either human or pig apolipoprotein A-I (apo-A-I) using small liposomes as substrate. Human apoA-I, however, caused a higher esterification rate for both enzymes. Using apoA-I and small liposomes as a substrate, the addition of apoC-II up to 4 micrograms/ml had no effect on the LCAT reaction, but above this concentration LCAT was inhibited. Small liposomes with phosphatidylcholine/cholesterol molar ratios of 3:1 up to 8.4:1 did not show any significant differences in the LCAT reaction, when used as substrates in the presence of various amounts of apoA-I and albumin. In contrast, the LCAT activity was significantly reduced by liposomes with phosphatidylcholine/cholesterol molar ratios below 3:1.


An abbreviated area-under-the-curve monitoring for tacrolimus in patients with liver transplants.
This study aims to assess the predictability of individual tacrolimus (FK) concentrations at different time points for the area under the curve (AUC) and to find the best sampling time for the abbreviated AUC to predict the total body exposure of FK. A total of 23 FK blood concentration versus time profiles (11 blood samples per 12 hours) was studied in 12 stable patients with liver transplants at steady state. Each AUC was calculated by the trapezoidal rule, and the relationship between individual concentrations or abbreviated AUC and total AUC was determined by linear regression. The trough concentrations from the morning dose predict AUC better than the trough concentration from the evening dose (r2 = 0.71 for morning dose and r2 = 0.35 for evening dose). In the case of single drug concentration, the 4-hour concentration could predict the total AUC reasonably well (r2 = 0.73). From stepwise multiple regression, the abbreviated AUC at 1, 2.5, 6, and 9 hours could predict the total AUC most accurately (r2 = 0.99). This study shows that the four levels at 1, 2.5, 6, and 9 hours or 1, 4, and 12 hours as an abbreviated AUC is as good as a full pharmacokinetic study. Alternatively, 4-hour concentration is a good predictor of the total body exposure of FK in the stable patients with liver transplants.


[Preparation of the promotion of therapeutic studies as an open planning process].
During the preparation of the government program "Health Research and Development", which was started in 1978, an attempt was made to involve the scientific community directly in establishing priorities for research on rheumatic diseases. At a planning conference open to all interested research scientists the following questions were considered: 1. What are the methodological requirements for therapeutic trials? 2. What are the open questions in the field of clinical rheumatology and which of them should be given priority? 3. What are the conditions for running multicenter therapeutic trials successfully? This paper describes the methodology and the results of the analysis of research needs and priorities and discusses the special problems of clinical rheumatology research in the Federal Republic of Germany.


What proportion of patients with psychosis is willing to take part in research? A mental health electronic case register analysis.
The proportion of people with mental health disorders who participate in clinical research studies is much smaller than for those with physical health disorders. It is sometimes assumed that this reflects an unwillingness to volunteer for mental health research studies. We examined this issue in a large sample of patients with psychosis. Cross-sectional study. Anonymised electronic mental health record data from the South London and Maudsley NHS Foundation Trust (SLaM). 5787 adults diagnosed with a psychotic disorder. Whether approached prior to 1 September 2014 for consent to be approached about research participation. Number of days spent in a psychiatric hospital, whether admitted to hospital compulsorily, and total score on the Health of the Nation Outcome Scale (HoNOS) between 1 September 2014 and 28 February 2015 with patient factors (age, gender, ethnicity, marital status and diagnosis) and treating clinical service as covariates. 1187 patients (20.5% of the total sample) had been approached about research participation. Of those who were approached, 773 (65.1%) agreed to be contacted in future by researchers. Patients who had been approached had 2.3 fewer inpatient days (95% CI -4.4 to -0.3, p=0.03), were less likely to have had a compulsory admission (OR 0.65, 95% CI 0.50 to 0.84, p=0.001) and had a better HoNOS score (β coefficient -0.9, 95% CI -1.5 to -0.4, p=0.001) than those who had not. Among patients who were approached, there was no significant difference in clinical outcomes between those agreed to research contact and those who did not. About two-thirds of patients with psychotic disorders were willing to be contacted about participation in research. The patients who were approached had better clinical outcomes than those who were not, suggesting that clinicians were more likely to approach patients who were less unwell.


The experiences of participating in winter among youths with a physical disability compared with their typically developing peers.
Having a physical disability and using a wheelchair can create difficulties in navigating the physical and built environment, especially during winter when snow and ice become problematic. Little is known about the experiences of winter among youth who use an assistive mobility device. This study aimed to understand how youth with a physical disability experience winter, compared with typically developing peers. A purposive sample of 25 youths (13 with a physical disability; 12 typically developing) completed a 2-week weather journal and photographs in two Canadian cities during winter. These data were used to guide semi-structured interviews with participants. Youths with disabilities experienced many similar challenges in winter, such as health and safety concerns and accessibility issues, compared with typically developing youth - but to a greater extent. Youths with disabilities reported more challenges going outdoors during winter and negative psychosocial impacts, including loneliness and increased dependence, compared with peers without a disability. They also, however, described developing several adaptive strategies to cope with these challenges. There is a strong need to remove physical and environmental barriers to facilitate the participation and inclusion of youth with disabilities in winter.


Effects of stimulus intensity, cervical cord tractotomies and cerebellectomy on somatosensory evoked potentials from skin and muscle afferents of cat hind limb.
The somatosensory evoked potentials (SEPs) recorded from the sensory cortex were investigated by using graded stimulation of skin and muscle nerves from contralateral hind limb in the cat. Sections were made of the middle cervical cord to assess the pathways involved in mediating SEPs evoked by large and small diameter fibers. Dorsal column (DC) section caused a decrease of SEPs from skin group I afferents, and a small increase in those from group I muscle afferents. A subsequent section of dorso-lateral fasciculus (DLF) further decreased SEPs from skin and eliminated SEPs from muscle, evoked at low stimulus intensity. When the stimulus recruited group III fibres, SEPs were still present after DC and DLF section, both from skin and muscle nerves. Section of ALT in addition to DC confirmed a major role played by DLF (mainly spino-cervical tract of Morin) in transmitting impulses from muscle afferents; the role of DLF in mediating potentials evoked from skin is less remarkable than that of DC. Cerebellectomy did not change any SEP, however evoked. Previous results in the literature are discussed, taking into account the methodologies employed by various authors, and the possible interactions among pathways mediating SEPs.


Malignancy risk of thyroid nodules: quality assessment of the thyroid ultrasound report.
Thyroid nodules are a challenge in clinical practice and thyroid ultrasonography is essential for assessing the risk of malignancy. The use of ultrasound-based malignancy risk classification systems has been recommended by several scientific societies but radiologist's adherence to these guidelines may vary. The authors aimed to analyze the quality of the information provided by the thyroid ultrasound report, to assess the malignancy risk of thyroid nodules, in Portugal. Multicenter and retrospective study, conducted in three of the five Portuguese NUTS2 corresponding to about 88.3% of the mainland population. We included 344 consecutive unselected participants aged ≥ 18 years who underwent thyroid ultrasonography in 2019. The description of six features of the dominant thyroid nodule was analyzed: maximum size, shape, margins, composition, echogenicity and echogenic foci. A utility score, including these six features, was used as an indicator of the report's quality. A score of 4 was considered as a minimum value. Maximum diameter was reported for all nodules. Shape, margins, composition, echogenicity and echogenic foci were reported in 8.1%, 25.0%, 76.5%, 53.2% and 20.9%, respectively. Only 21.8% of the nodules had a score ≥ 4. At least one of four suspicious features, including marked hypoechogenicity, microcalcifications, irregular margins and non-oval shape, was identified in 8.7% of the nodules. Cervical lymph nodes' status was reported in 93% of the exams. The risk category was only reported in 7.8% of the participants. The adherence of Portuguese radiologists to a standardized reporting model and to an ultrasound-based malignancy risk stratification system is still low and has implications for the correct characterization of the malignancy risk of nodules and the decision to perform fine-needle aspiration biopsy.


A role for Salmonella typhimurium cbiK in cobalamin (vitamin B12) and siroheme biosynthesis.
The role of cbiK, a gene found encoded within the Salmonella typhimurium cob operon, has been investigated by studying its in vivo function in Escherichia coli. First, it was found that cbiK is not required for cobalamin biosynthesis in the presence of a genomic cysG gene (encoding siroheme synthase) background. Second, in the absence of a genomic cysG gene, cobalamin biosynthesis in E. coli was found to be dependent upon the presence of cobA(P. denitrificans) (encoding the uroporphyrinogen III methyltransferase from Pseudomonas denitrificans) and cbiK. Third, complementation of the cysteine auxotrophy of the E. coli cysG deletion strain 302delta a could be attained by the combined presence of cobA(P. denitrificans) and the S. typhimurium cbiK gene. Collectively these results suggest that CbiK can function in fashion analogous to that of the N-terminal domain of CysG (CysG(B)), which catalyzes the final two steps in siroheme synthesis, i.e., NAD-dependent dehydrogenation of precorrin-2 to sirohydrochlorin and ferrochelation. Thus, phenotypically CysG(B) and CbiK have very similar properties in vivo, although the two proteins do not have any sequence similarity. In comparison to CysG, CbiK appears to have a greater affinity for Co2+ than for Fe2+, and it is likely that cbiK encodes an enzyme whose primary role is that of a cobalt chelatase in corrin biosynthesis.


Effects of lethal and sublethal concentrations of the herbicide, triclopyr butoxyethyl ester, in the diet of zebra finches.
Lethal and sublethal effects of dietary triclopyr butoxyethyl ester (TBEE) on zebra finches (Poephila guttata Gould) were determined in laboratory experiments conducted between 8 January and 1 May 1991. The 8-day median lethal dietary concentration, LC50 (95% confidence interval), of TBEE to zebra finches was 1,923 (1,627 to 2,277) mg/kg. In the sublethal effects experiment, when birds were exposed to 500 mg/kg TBEE in the diet for 29 days, food consumption and body weight were significantly depressed (P < 0.05). Similar prolonged exposures to 50 and 150 mg/kg TBEE in the diet had no significant effect on food consumption or body weight (P > 0.05). Perch-hopping activity was depressed relative to controls in the 500 mg/kg group, and elevated in the 150 mg/kg group, but neither of these differences was significantly (P > 0.05). Disappearance of TBEE residues from treated seeds over the 29 day experimental period followed an exponential decay model, with half-lives in the order of 15 to 18 days. On the basis of our observation that TBEE had no significant adverse effects at a concentration greater than the maximum expected environmental concentration, we propose that forestry applications of triclopyr at registered dosage rates pose little risk to wild songbirds.


Cumulene-like bridged indeno[1,2-b]fluorene π-conjugated polymers synthesized on metal surfaces.
Among the plethora of polycyclic structures that have emerged in recent years, indenofluorenes comprise a unique class of compounds due to their potential in organic electronic systems such as OLEDs, OFETs, and OPVCs. However, the synthesis of fully conjugated indenofluorenes without bulky groups on the apical carbons under standard chemistry conditions is not easily accessible. In this regard, on-surface synthesis has appeared as a newly developing field of research, which exploits the use of well-defined solid surfaces as confinement templates to initiate and develop chemical reactions. Here, we demonstrate the successful fabrication of indeno[1,2-b]fluorene π-conjugated polymers linked via cumulene-like connections on well-defined metallic surfaces under ultra-high vacuum conditions. The structure and electronic properties of the formed polymers have been precisely characterized by scanning tunneling microscopy, noncontact atomic force microscopy and scanning tunneling spectroscopy, complemented by computational investigations.


LC-MS determination of triazolam and its hydroxy metabolites in mouse dried blood spots: application to transgenic mouse pharmacokinetic studies.
The objective of this study was to develop a LC-MS/MS method for the simultaneous determination of triazolam (TRZ) and its two hydroxy metabolites in transgenic mouse dried blood spots (DBS) using BALB/c mouse blood as a surrogate biomatrix. The DBS method involved spotting volume of 10 μl using Ahlstrom 226 sample collection cards. A 'whole spot' analysis (6-mm punch) involved extraction of analytes using water and acetonitrile containing an internal standard. DBS samples were analyzed by a validated LC-MS/MS method with a run time of 4 min. This validated LC-MS/MS method using DBS extraction was applied to quantitation of TRZ, α-hydroxytriazolam and 4-hydroxytriazolam in a CYP3A4 transgenic mouse oral pharmacokinetic study of TRZ.


Factors affecting the outcome of osteochondral autografting (mosaicplasty) in articular cartilage defects of the knee joint: retrospective analysis of 152 cases.
The purpose of this retrospective study was to evaluate the results and prognostic factors affecting the outcome of osteochondral autografting (mosaicplasty) in articular cartilage defects of the knee joint. One hundred fifty-two patients who underwent mosaicplasty for femoral condylar cartilage defects (modified Outerbridge classification: Grade III and IV) of the knee joint between 1998 and 2007 in our institution were included. There were 126 male and 26 female patients with a mean age of 24.8 ± 4.6 years. The average size of the lesion was 2.7 ± 0.7 cm(2). Of these patients, 33 had concomitant meniscal and/or cruciate ligament injuries which were treated simultaneously. All patients were followed up with a mean of 18.2 ± 4.2 months (range 12-24 months) using Lysholm knee score. We analyzed the relationship between the outcome variable (Lysholm knee score at the final follow-up) and the predictor variables (age, gender, lesion size, lesion grade, localization, accompanying intra-articular injuries and duration of follow-up). The mean preoperative Lysholm knee score was 55.2 ± 3.6 points and increased to 88.2 ± 2.5 points at the final follow-up. There was a significant increase in Lysholm score during follow-up period (p = 0.0001). The results were excellent in 2 cases (1.3 %), good in 144 cases (94.7 %) and fair in 6 cases (3.9 %). No patients had infection, systemic complication and revision surgery. Backward regression analysis showed that age, lesion size, localization and associated intraarticular injuries are the only predictors of the final Lysholm knee score in best fit model (R (2) = 0.442, p = 0.0001). The linear regression equation was (Lysholm score at final follow-up) = 93.4 - [0.2 (age of patient) + 0.8 (lesion size) + 0.9 (localization) + 2.8 (presence of associated intraarticular injuries)]. Mosaicplasty is an effective technique for the treatment of articular cartilage defects of the knee joint which restores the joint function in a short period of follow-up. Furthermore, age, lesion size, localization, and concomitant surgical interventions are major factors affecting the final outcome. The final knee score deteriorates as the age of the patient and size of the lesion increases. Furthermore, concomitant surgical interventions and lesions located on the medial femoral condyle have a negative effect on the final knee score.


Novel approaches to imaging basal cell carcinoma.
The gold standard of diagnosis for nonmelanoma and melanoma skin cancer has been skin biopsy with routine paraffin embedded hematoxylin and eosin histopathology. This practice is frequently carried out on suspicious lesions to rule out a malignant process. Therefore, as a result, many biopsies are done on benign lesions. Unlike other fields of medicine that rely on noninvasive imaging modalities, the use of imaging devices in dermatology has not been as robust. This has been mainly due to the limited resolution offered by imaging devices that is needed to detect malignant changes in the cutaneous layers. However, the demand for more efficient in vivo and ex vivo imaging tools to reduce the amount of biopsies have led to new areas of investigation using noninvasive modalities to augment the clinical diagnosis of skin cancer. The use of noninvasive imaging both in vivo and ex vivo has the potential to increase efficiency of diagnosis and management, decrease healthcare cost, improve clinical care and enhance patient satisfaction.


First-round accreditation and pass rates on licensing examination at different medical schools in China: Closing the performance gap.
Although the accreditation approach is widely used to ensure the quality of medical education in many countries, there is scant empirical evidence on whether and how it improves actual medical school performance. We focused on conditions in China, which introduced an accreditation system during the 2010s. Specifically, we examined the relationship between first-round accreditation and actual performance based on the results of medical licensing examinations. Referring to organisation theory, we hypothesised that the impacts of accreditation would depend on existing performance gaps. In 2022, we analysed panel data from 105 Chinese medical schools during accreditation (2012 to 2021) and pass rates on medical licensing examinations (2011 to 2019), as matched into 834 school-year records in a window of years before and after accreditation. We employed fixed-effects regression models with a comparison group to exclude factors that may have confounded the impacts of accreditation time. We also demonstrated the heterogeneous effects of accreditation by tier and performance gap of medical schools. The conservative estimates showed a substantial cumulative improvement (over 15 percentage points) in pass rates during the years before accreditation, with no clear trend indicating performance drops in the years after accreditation. Lower-tiered medical schools gained greater benefits from accreditation. Medical schools with a larger prior performance gap achieved a greater percentage point increase in pass rates with the passage of time in pre-accreditation years. This is the first empirical study to investigate whether accreditation has bridged performance gaps among medical schools. The results support the value of accreditation in China, a country that recently established the system, and might work as a substitute for missing information on early accreditation history in countries with long-established accreditation systems. We encourage more studies in countries that have recently introduced accreditation systems.


Breast milk composition in Ethiopian and Swedish mothers. I. Vitamin A and beta-carotene.
The vitamin A and beta-carotene contents of breast milk were determined at different stages of lactation in three population groups: nonprivileged Ethiopian, privileged Ethiopian, and Swedish mothers. In addition, a fractionation of vitamin A giving the proportion of retinol was performed. The concentrations of retinol-binding protein (RBP) and (in part of the material) beta-carotene and prealbumin in plasma were also measured. The mean concentrations of vitamin A and beta-carotene in the milk from the Swedish mothers (period 0.5 to 6.5 months) were in the range of 40.0 to 53.1 and 16.3 to 20.8 mug/100 ml, respectively. For the privileged Ethiopian mothers (period 0.5 to 3.5 months) the corresponding ranges were 36.2 to 36.4 and 26.2 to 28.1 mug/100 ml and for the nonprivileged Ethiopian mothers (period 0.5 to 6.5 months) 28.1 to 33.1 and 23.9 to 25.6 mug/100 ml. Only the nonprivileged Ethiopian mothers were examined during a later stage of lactation (6.5 to 11.5 and 11.5 to 23.5 months). The concentrations of vitamin A and beta-carotene in their milk showed a downward trend. The proportion of retinyl ester (percentage of total vitamin A content) was significantly higher in the milk of Swedish mothers than in privileged and nonprivileged Ethiopian mothers. In the Swedish mothers retinol constituted 3.5% of the total vitamin A content of the milk; in Ethiopian mothers it was 15 to 30%. Determination of RBP in plasma showed normal values for Swedish mothers and lowered values for Ethiopian mothers--particularly the nonprivileged, in whom 14 of 81 values were below 20 mug/ml. RBP was demonstrated in colostrum, but only in a low concentration (in the order of 5 mug/ml).


Antioxidant Barrier and Oxidative Damage to Proteins, Lipids, and DNA/RNA in Adrenal Tumor Patients.
This study is the first to assess redox balance, glutathione metabolism, and oxidative damage to RNA/DNA, proteins, and lipids in the plasma/serum and urine of patients with adrenal masses. The study included 70 patients with adrenal tumors divided into three subgroups: incidentaloma (n = 30), pheochromocytoma (n = 20), and Cushing's/Conn's adenoma (n = 20), as well as 60 healthy controls. Blood and urine samples were collected before elective endoscopic adrenalectomy. Antioxidant defense capacity was significantly decreased (serum/plasma: superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH), uric acid (UA); urine: SOD, GSH, UA) in patients with adrenal masses. The oxidative damage to proteins (advanced glycation end products (AGE), advanced oxidation protein products (AOPP)) and lipids (lipid hydroperoxides (LOOH), and malondialdehyde (MDA)) was higher in the plasma and urine of these patients. Plasma MDA and DNA/RNA oxidation products, with high sensitivity and specificity, can help to diagnose pheochromocytoma. This biomarker differentiates patients with pheochromocytoma from Cushing's/Conn's adenoma as well as from heathy controls. Plasma RNA/DNA oxidation was also positively correlated with urine metanephrine. Oxidative stress can play a crucial role in adrenal tumors. However, further studies are required to clarify the role of redox signaling in adrenal masses.


Resin acids as inducible chemical defences of pine seedlings against chewing insects.
Inducibility of defences in response to biotic stimuli is considered an important trait in plant resistance. In conifers, previous research has mostly focused on the inducibility of the volatile fraction of the oleoresin (mono- and sesquiterpenes), leaving the inducibility of the non-volatile resin acids largely unexplored, particularly in response to real herbivory. Here we investigated the differences in the inducibility of resin acids in two pine species, one native from Europe (Pinus pinaster Ait.) and another from North America (Pinus radiata D. Don), in response to wounding by two European insects: a bark chewer, the pine weevil (Hylobius abietis L.), and a defoliator, the pine processionary caterpillar (Thaumetopoea pityocampa Schiff.). We quantified the constitutive (control) and induced concentrations of resin acids in the stem and needles of both pine species by gas chromatography techniques. Both pine species strongly increased the concentration of resin acids in the stem after pine weevil feeding, although the response was greater in P. pinaster than in P. radiata. However, systemic defensive responses in the needles were negligible in both pine species after pine weevil feeding in the stem. On the other hand, P. radiata locally reduced the resin acid concentration in the needles after pine caterpillar feeding, whereas in P. pinaster resin acid concentration was apparently unaffected. Nevertheless, systemic induction of resin acids was only observed in the stem of P. pinaster in response to pine caterpillar feeding. In summary, pine induced responses were found highly compartmentalized, and specific to herbivore identity. Particularly, plant defence suppression mechanisms by the pine caterpillar, and ontogenetic factors might be potentially affecting the induced response of resin acids in both pine species.


Time-varying networks of ERPs in P300-speller paradigms based on spatially and semantically congruent audiovisual bimodality.
In the P300-speller paradigm using spatially and semantically congruent audiovisual (AV) stimuli, AV stimuli elicited significantly higher event-related potential (ERP) amplitudes than those for a single visual (V) stimulus. Nevertheless, it remains unclear whether ERPs in AV and V spelling paradigms are generated with identical brain network architecture. In this study, we constructed time-varying networks for ERPs in AV and V spelling paradigms based on adaptive directed transfer function to investigate the dynamic processes underpinning the processing of stimuli in the two spelling paradigms. Our analysis revealed that early AV integration, AV spatial and semantic information, and late AV integration enhanced activation in attention-related areas between 40–160 ms, areas associated with attention to target stimuli between 200–280 ms, and areas associated with decision-making between 320–520 ms, respectively. Left temporal areas were associated with AV spatial-semantic information-processing and late AV integration, the activation of which impacted the activation of brain areas associated with attention (P3a) and decision-making (P3b). In addition, the ability and efficiency of information transmission from brain networks in the AV spelling paradigm were significantly stronger than those in the V spelling paradigm between 40 and 160 ms, 200 and 280 ms, and 320 and 520 ms. This work provides a theoretical basis for deepening our understanding of the neural mechanisms underscoring ERPs production in the AV P300-speller paradigm as well as a theoretical reference for further optimization of the induced paradigm based on AV stimuli and improves the performance of BCI system.


The Role of Artificial Intelligence Model Documentation in Translational Science: Scoping Review.
Despite the touted potential of artificial intelligence (AI) and machine learning (ML) to revolutionize health care, clinical decision support tools, herein referred to as medical modeling software (MMS), have yet to realize the anticipated benefits. One proposed obstacle is the acknowledged gaps in AI translation. These gaps stem partly from the fragmentation of processes and resources to support MMS transparent documentation. Consequently, the absence of transparent reporting hinders the provision of evidence to support the implementation of MMS in clinical practice, thereby serving as a substantial barrier to the successful translation of software from research settings to clinical practice. This study aimed to scope the current landscape of AI- and ML-based MMS documentation practices and elucidate the function of documentation in facilitating the translation of ethical and explainable MMS into clinical workflows. A scoping review was conducted in accordance with PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines. PubMed was searched using Medical Subject Headings key concepts of AI, ML, ethical considerations, and explainability to identify publications detailing AI- and ML-based MMS documentation, in addition to snowball sampling of selected reference lists. To include the possibility of implicit documentation practices not explicitly labeled as such, we did not use documentation as a key concept but as an inclusion criterion. A 2-stage screening process (title and abstract screening and full-text review) was conducted by 1 author. A data extraction template was used to record publication-related information; barriers to developing ethical and explainable MMS; available standards, regulations, frameworks, or governance strategies related to documentation; and recommendations for documentation for papers that met the inclusion criteria. Of the 115 papers retrieved, 21 (18.3%) papers met the requirements for inclusion. Ethics and explainability were investigated in the context of AI- and ML-based MMS documentation and translation. Data detailing the current state and challenges and recommendations for future studies were synthesized. Notable themes defining the current state and challenges that required thorough review included bias, accountability, governance, and explainability. Recommendations identified in the literature to address present barriers call for a proactive evaluation of MMS, multidisciplinary collaboration, adherence to investigation and validation protocols, transparency and traceability requirements, and guiding standards and frameworks that enhance documentation efforts and support the translation of AI- and ML-based MMS. Resolving barriers to translation is critical for MMS to deliver on expectations, including those barriers identified in this scoping review related to bias, accountability, governance, and explainability. Our findings suggest that transparent strategic documentation, aligning translational science and regulatory science, will support the translation of MMS by coordinating communication and reporting and reducing translational barriers, thereby furthering the adoption of MMS.


The glucagon receptor is required for the adaptive metabolic response to fasting.
Glucagon receptor (Gcgr) signaling maintains hepatic glucose production during the fasting state; however, the importance of the Gcgr for lipid metabolism is unclear. We show here that fasted Gcgr-/- mice exhibit a significant increase in hepatic triglyceride secretion and fasting increases fatty acid oxidation (FAO) in wild-type (WT) but not in Gcgr-/- mice. Moreover fasting upregulated the expression of FAO-related hepatic mRNA transcripts in Gcgr+/+ but not in Gcgr-/- mice. Exogenous glucagon administration reduced plasma triglycerides in WT mice, inhibited TG synthesis and secretion, and stimulated FA beta oxidation in Gcgr+/+ hepatocytes. The actions of glucagon on TG synthesis and FAO were abolished in PPARalpha-/- hepatocytes. These findings demonstrate that the Gcgr receptor is required for control of lipid metabolism during the adaptive metabolic response to fasting.


Pavietin, a coumarin from Aesculus pavia with antifungal activity.
A new prenylated coumarin, S-6-[2-(hydroxymethyl)butoxy]-7-hydroxy-4-methyl-2 H-chromen-2-one ( 1), named pavietin, has been isolated from the leaves of an Aesculus pavia genotype along with three known flavonol glycosides, quercetin 3- O-alpha-rhamnoside (quercitrin, 2), quercetin 3- O-alpha-arabinoside ( 3), and isorhamnetin 3- O-alpha-arabinoside (distichin, 4). The chemical structure of compound 1 was determined by chemical and spectroscopic methods, inclusive of UV, MS, and 1D and 2D NMR experiments. It showed appreciable antimicrobial properties against several pathogens, displaying a significant antifungal activity toward one of the main fungal parasites of Aesculus species, Guignardia aesculi. The same biological tests performed with a mixture of flavonoids 2- 4 resulted in weak or no activity. Compound 1 was undetectable in Aesculus hippocastanum, a closely related species lacking resistance to fungal pathogens. The possible role of 1 in plant resistance is discussed.


Abrogation of factor-dependence in two IL-3-dependent cell lines can occur by two distinct mechanisms.
We have investigated the mechanisms of abrogation of factor-dependence of lymphoid (FL5.12) and myeloid (FDC-P1) interleukin-3 (IL-3)-dependent cell lines following infection of the cells with retroviruses that encode different oncogenes and immediate selection of IL-3-independent growth. As previously reported by others, Abelson-MuLV (Ab-MuLV) transforms both cell lines to factor-independence, and the transformed cells express the viral oncogene, do not produce IL-3, and are tumorigenic. In contrast, IL-3-independent lymphoid and myeloid cell lines recovered after infection with retroviruses that encode v-src or v-fms oncogenes lacked the v-src or v-fms provirus. Three of seven IL-3-independent transformants were rearranged at the IL-3 locus, produced IL-3-specific mRNA, secreted IL-3 into the culture medium, and grew better in the presence of IL-3. These IL-3-independent transformants produced tumors upon inoculation into nude mice, albeit with longer latent periods than Ab-MuLV transformants. The expression of hematopoietic cell markers was compared in parental and IL-3-independent transformants by immunofluorescence and analysis of mRNA levels. Significant elevation of LFA-1 and MHC class I molecules and loss of expression of IL-2-receptor molecules was detected in most IL-3-independent transformants. These differences in antigen expression indicate that additional phenotypic changes accompany transformation to factor-independence.


Simultaneous maximization of cell permeabilization and viability in single-cell electroporation using an electrolyte-filled capillary.
A549 cells were briefly exposed to Thioglo-1, which converts thiols to fluorescent adducts. The fluorescent cells were exposed to short (50-300 ms) electric field pulses (500 V across a 15 cm capillary) created at the tip of an electrolyte-filled capillary. Fluorescence microscopy revealed varying degrees of cell permeabilization depending on the conditions. Longer pulses and a shorter cell-capillary tip distance led to a greater decrease in the cell's fluorescence. Live/dead (calcein AM and propidium iodide) testing revealed that a certain fraction of cells died. Longer pulses and shorter cell-capillary tip distances were more deadly. An optimum condition exists at a cell-capillary tip distance of 3.5-4.5 microm and a pulse duration of 120-150 ms. At these conditions, >90% of the cells are permeabilized and 80-90% survive.


[Unusual foreign body aspiration].
Tracheobronchial foreign body aspiration in adults is rare when compared to children. In this case report, 76 year old female patient who aspirated a screw of tracheostomy cannula which was taken out by fiberoptic bronchoscopy (FOB) was presented. This case showed us that education of patients about stoma care is important. The FOB can be used safely to get foreign body from distal airways.


Effect of abdominal infections on peritoneal and systemic production of interleukin 6 and monocyte chemoattractant protein-1.
The aim of the study was to compare peritoneal and systemic production of interleukin 6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) in uninfected patients and in patients with peritonitis. Peritoneum was excised at laparotomy for acute peritonitis (n = 22) or noninfectious reasons (n = 61), and was incubated with or without lipopolysaccharide (LPS). Mediator concentrations in the culture-supernatants, in the patients' serum, and in plasmasupernatants of LPS-stimulated whole blood were related to outcome. Spontaneous production of IL-6 by the peritoneum was increased in infected patients compared with uninfected patients. In contrast to IL-6, LPS-stimulated production of MCP-1 was significantly less in infected patients. Serum concentrations of both mediators were higher in infected patients and the highest concentrations of MCP-1 were in patients who died. LPS-stimulated production of IL-6 in whole blood was least, whereas that of MCP-1 was greatest in infected patients who died. These contrasting results for local and systemic production of mediators illustrate the compartmentalized immune response to intra-abdominal infection.


An international survey of EEG use in the neonatal intensive care unit.
To examine the extent of EEG monitoring in neonatal intensive care units (NICUs), and to survey the level of experience and training of those using it. A web-based survey, the link to which was circulated via e-mail, personal contact, specialist societies and professional groups. Survey data were exported to SPSS for analysis. In total 210 surveys were analysed; 124 from Europe, 54 from the US. Ninety percent of respondents had access to either EEG or aEEG monitoring; 51% had both. EEG was mainly interpreted by neurophysiologists (72%) whereas aEEG was usually interpreted by neonatologists (80%). Only 9% of respondents reported that they felt 'very confident' in their ability to interpret aEEG/EEG with 31% reporting that they were 'not confident'. Half had received no formal training in EEG. Both aEEG and conventional EEG were used extensively in the NICUs surveyed for this study. Most of the survey respondents were not confident in their ability to interpret EEGs despite the fact that they used monitoring routinely. There is an urgent need for a structured and appropriately targeted training programme in EEG methodologies and EEG interpretation for neonatal intensive care unit staff.


The Clinical Value of Breast Specific Gamma Imaging and Positron Imaging: An Update.
In the management of patients with breast cancer (BC), a mammography contributed to screen an early-stage patient, to plan a therapy strategy, to evaluate a therapy outcome, to detect a recurrence, and to reduce a mortality. Currently, various imaging modalities, such as CT, MR, Ultrasound (US), SPECT/CT, PET/CT, PET/MR have been utilized for the management of BC patients. In order to overcome a limited spatial resolution and sensitivity of whole-body systems in nuclear medicine imaging, dedicated breast imaging modalities were developed. One is a gamma imaging system with single/dual head scintillation detectors or semiconductor detectors associated with light compression device for breast parenchyma. Radiopharmaceutical for the gamma imaging is 99mTc-sestamibi. Another is a positron imaging system with opposite-type panel detectors and ring-shaped type detectors. Radiopharmaceutical for positron imaging is 18F-fluorodeoxyglucose. The breast-specific gamma and positron imaging systems were utilized mainly to detect small lesions less than 1 cm in diameter especially in patients with dense breast, to evaluate an effect of preoperative neo-adjuvant therapy, to plan surgical procedures (conservative-surgery vs mastectomy), and to detect a recurrence. By combining higher sensitivity and spatial resolution scanners with new radiopharmaceuticals, an information on molecular-level pathology of BC is increasingly available in an individual patient. This article reviewed clinical impact and future perspective of this field.


Midazolam infusions in critically ill patients.
Fifty consecutive patients were studied prospectively to assess the effects of a continuous intravenous infusion of midazolam hydrochloride for sedation in patients requiring intensive care. Patient comfort was acceptable in all patients. However, to maintain the same degree of sedation it was necessary to increase the daily dose of midazolam indicating that benzodiazepine tolerance may have been developing. The time taken to awaken following cessation of a midazolam infusion was prolonged in some patients. In those patients with renal failure the mean (+/- SD) value was 44.6 +/- 42.5 h compared to patients without renal failure in whom it was 13.6 +/- 16.4 h (P less than 0.01). Two patients with combined hepatic and renal failure took 124 and 140 h to awaken. Continuous intravenous infusion of midazolam offers good patient comfort but increasing dose requirements in critically ill patients may lead to drug accumulation and delayed awakening. The risks of cumulation may be increased if the drug is given by continuous infusion for prolonged periods without intermittent assessment of the patient's conscious state.


In vivo and in vitro assessment of mirtazapine pharmacokinetics in cats with liver disease.
Liver disease (LD) prolongs mirtazapine half-life in humans, but it is unknown if this occurs in cats with LD and healthy cats. To determine pharmacokinetics of administered orally mirtazapine in vivo and in vitro (liver microsomes) in cats with LD and healthy cats. Eleven LD and 11 age-matched control cats. Case-control study. Serum was obtained 1 and 4 hours (22 cats) and 24 hours (14 cats) after oral administration of 1.88 mg mirtazapine. Mirtazapine concentrations were measured by liquid chromatography with tandem mass spectrometry. Drug exposure and half-life were predicted using limited sampling modeling and estimated using noncompartmental methods. in vitro mirtazapine pharmacokinetics were assessed using liver microsomes from 3 LD cats and 4 cats without LD. There was a significant difference in time to maximum serum concentration between LD cats and control cats (median [range]: 4 [1-4] hours versus 1 [1-4] hours; P = .03). The calculated half-life of LD cats was significantly prolonged compared to controls (median [range]: 13.8 [7.9-61.4] hours versus 7.4 [6.7-9.1] hours; P < .002). Mirtazapine half-life was correlated with ALT (P = .002; r = .76), ALP (P < .0001; r = .89), and total bilirubin (P = .0008; r = .81). The rate of loss of mirtazapine was significantly different between microsomes of LD cats (-0.0022 min-1 , CI: -0.0050 to 0.00054 min-1 ) and cats without LD (0.01849 min-1 , CI: -0.025 to -0.012 min-1 ; P = .002). Cats with LD might require less frequent administration of mirtazapine than normal cats.


Studies in diabetic pregnancy. I. Serum lipids.
The serum lipid values at different stages of pregnancy in twenty-six pregnany diabetic women attending a special antenatal clinic at the Department of Obstetrics and Gynecology, were compared with the corresponding values in four control series composed of non-diabetic pregnant women. Control series were studied at weeks 10, 22, 34 and after delivery, respectively. Serum triglycerides were higher in the diabetic women at week 10 (p less than 0.01), week 34 (p less than 0.05) and after delivery (p less than 0.05). Furthermore, in the diabetic women, infant birth weights were correlated (r=0.52, p=0.05) with maternal serum triglyceride values at week 31. Women with the highest serum triglyceride values (greater than 250 mg/100 ml) were delivered of infants with a higher birth weight (p less than 0.05) than those women with lower serum triglyceride values (less than 250 mg/100 ml). Intra-uterine deaths (n=4) were not related to maternal serum triglyceride values, but mean blood glucose values (during the whole pregnancy) were higher (p less than 0.001) in mothers with intra-uterine deaths. Elevated plasma free fatty acids (FFA) in the diabetic mother would be a possible cause for elevated serum triglycerides through increased liver triglyceride synthesis, while in the fetus an excess of plasma FFA (passing through the placental barrier) together with normal or elevated plasma insulin would be a likely explanation for increased triglyceride synthesis in adipose tissue and thereby of increased fat depots and body weight.


The effect of praziquantel treatment on glutathione concentration in Schistosoma mansoni.
A fluorescent dye monochlorobimane (MCB) that binds glutathione (GSH) was used as a tool for measuring the concentration of GSH in skin and mechanically-transformed schistosomula. The specificity of MCB binding to GSH was confirmed by thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). The MCB binding to GSH is an energy-dependent process since no labelling could be seen at low temperature. When 24-h-old schistosomula were depleted of GSH by buthionine sulfoximine (a specific inhibitor of GSH synthesis) for 18 h, a significant decrease (P < 0.001) in fluorescence was observed. PZQ treatment of the schistosomula after first labelling the parasites with MCB did not greatly affect MCB binding to GSH. However, when the 24-h-old schistosomula were first PZQ treated and afterwards labelled with MCB, the pattern of labelling was identical to that of those of the non-labelled parasites. When 24-h-old schistosomula were first PZQ treated, washed and labelled in the presence of 1 mM GSH, the level of fluorescence was recovered. These results suggest that PZQ depletes GSH from schistosomula, and may render them susceptible to the host's immune system.


Evaluating a bacterial hypothesis in IBS using a modification of Koch's postulates: part 1.
It has recently been suggested that irritable bowel syndrome (IBS) symptoms are due partly to small intestinal bacterial overgrowth (SIBO). This "SIBO hypothesis" has led to the use of antibiotics to treat IBS. Koch's postulates have long been used to establish bacteria as a cause of diseases such as tuberculosis. Because SIBO is not a single organism, we use modified Koch's postulates to argue for antibiotics and an SIBO hypothesis in the pathophysiology of IBS. We show that there is evidence for SIBO, that it is culturable, that antibiotic elimination of the bacteria improves subjects clinically, and that when the bacteria return, the symptoms return. On the basis of proof of a bacterial cause of IBS, antibiotics may be a good choice of therapy.


The association between dental, general, and mental health status among underserved and vulnerable populations served at health centers in the US.
Vulnerable populations in underserved communities are disproportionately at high risk for multiple medical, dental, and behavioral health conditions. This study aims to: a) examine the occurrence of acute dental needs and b) investigate the association of acute dental needs and self-rated general and mental health status among the adult dentate health center population. This cross-sectional study analyzed data on adult patients (n = 5,035) from the 2014 Health Center Patient Survey, a nationally representative survey of health center patients. Multivariate logistic regression was used to assess the association of acute dental needs and a) self-rated general health status and b) mental health status. Approximately, two thirds of adult dentate heath center patients reported having an acute dental need. After adjusting for confounding factors, not having or having had health insurance that pays for dental care, general health status of fair or poor, and ever having a mental illness were associated with higher odds of having an acute dental need. The results highlight the role of health centers in addressing oral health disparities among vulnerable populations and the importance of a team-based multidisciplinary approach to ensuring the integration and coordination of oral health services within a comprehensive primary care delivery system.


Effect of β-hydroxy-β-methylbutyrate calcium on growth, blood parameters, and carcass qualities of broiler chickens.
Beta-hydroxy-β-methylbutyrate (HMB), the metabolite of leucine, plays an important role in muscle protein metabolism. To investigate the effect of dietary HMB calcium (HMB-Ca) on growth performance, breast muscle development, and serum parameters in broiler chickens, a total of two hundred seventy 1-d-old Arbor Acres male broiler chicks were randomly allotted into 3 dietary treatments supplemented with 0, 0.05%, or 0.1% HMB-Ca during the starter (1 to 21 d) and grower (22 to 42 d) period. The results showed that broilers fed 0.1% HMB-Ca diet had higher ADG during the starter or the whole period, and gain 148 g more BW than the chicks fed the control diet at 42 d of age (P < 0.05). At 21 d of age, birds receiving 0.1% HMB-Ca had more breast muscle yield, less abdominal fat than the control, and more dressing percentage than birds fed the control or 0.05% HMB-Ca diet (P < 0.05). At 42 d of age, 0.1% HMB-Ca increased breast muscle yield than the control and decreased abdominal fat compared with the control or 0.05% HMB-Ca group (P < 0.05). In comparison with the control, feeding 0.1% HMB-Ca increased the triiodothyronine, thyroxine, triiodothyronine/thyroxine ratio and decreased the serum uric acid level at d 21 (P < 0.05). At 42 d of age, serum thyroxine level was elevated in the 0.05% HMB-Ca treatment, and the uric acid concentration was significantly decreased by the 0.1% HMB-Ca-supplemented diet (P < 0.05). Dietary HMB-Ca did not affect the growth hormone or insulin content. This study suggested that dietary supplementation of HMB-Ca improved growth performance, stimulated the breast muscle development, and decreased the abdominal fat deposition in broiler chickens, and the favorable effects were more pronounced in the starter phase. The growth promotion effect of HMB-Ca may be partly related to the increased serum thyroid hormones in broiler chickens.


Acute neurological conditions during pregnancy and their management: a review.
Less vascular resistance, higher vascular permeability and improved cardiac output include anatomical and physiological changes related to pregnancy. These are needed to accommodate an increase in plasma volume and ensure significant organ infusion. Nevertheless, increases in oestrogen levels may lead to an increase in the risk of coagulation and thrombosis. Increased levels of progesterone increase the risk of thrombosis due to vasodilation, vascular stasis and edoema in these situations. The increased resistance in preeclampsia maternal systemic blood arteries can create high blood pressure that can interfere with blood flow in numerous organs (including liver, kidneys, brain and placenta). The risk of issues such as pulmonary edoema, placental abruption, pneumonia of aspiration, renal failure, hepatic failure and stroke in pregnant women is increased by Preeclampsia and eclampsia. Some peripheral neuropathies (carpal tunnel syndrome, peripheral facial palsy) and central neurological conditions (seizure, migraine, stroke, epilepsy) may become more common during pregnancy because of the exacerbation of the pre-existing neurologic condition or the onset of neurological disturbance caused by pregnancy physiological changes (such as headache or vascular disorders). During the three trimesters of pregnancy, neurological disorders are both peripheral and central. Therefore, an early and correct diagnosis is required to improve pregnancy care, treatment and perinatal outcomes. The aims of this paper are to identify, define and manage the most prevalent peripheral and centrally occurring neurological disorders in the pregnancy.


Analysis of human fecal material for autosomal and Y chromosome STRs.
Human stool samples from eight volunteers were stored under various conditions and extracted by three different procedures. Fecal material and tissue paper soiled with fecal material obtained from a crime scene were also extracted. Extracted DNA was amplified using the AmpFlSTR Profiler Plus, AmpFlSTR COfiler, and the AmpFlSTR Identifiler PCR amplification kits for the detection of the autosomal STR allelic patterns. DNA extracted from the male volunteers and from the soiled tissue paper evidence sample was also amplified using the Y-PLEX 6 and Y-PLEX 5 amplification kits. Analysis of the amplified products was carried out by capillary electrophoresis on the ABI PRISM 310 Genetic Analyzer. Autosomal and Y-STR profiles obtained from the fecal material were concordant with the results from the donors' buccal swabs.


Lidocaine and its analogues inhibit IL-5-mediated survival and activation of human eosinophils.
Eosinophils and cytokines active on eosinophils, especially IL-5, are believed to be critically involved in chronic allergic diseases. IL-5 activates eosinophils and enhances their survival in vitro by delaying apoptosis. In this study, we found that lidocaine and six analogues blunt responses of eosinophils to IL-5. Lidocaine and its derivatives inhibit IL-5-mediated eosinophil survival in a concentration-dependent manner (IC50 = 110 microM for 30 pg/ml IL-5). At suboptimal lidocaine concentrations, the eosinophil survival response to IL-5 shifts and more IL-5 is required to maintain survival. The inhibitory effect requires at least 24-h exposure of eosinophils to lidocaine, and the protein kinase C activator, PMA, completely reverses the inhibition. A multiparameter flow-cytometric analysis shows that lidocaine hastens the apoptosis of eosinophils normally delayed by IL-5. Lidocaine does not affect IL-5R expression or IL-5-induced protein tyrosine phosphorylation. Lidocaine also inhibits eosinophil survival mediated by IL-3 or granulocyte-macrophage CSF, although less potently than that mediated by IL-5. Furthermore, lidocaine inhibits eosinophil superoxide production stimulated by IL-5, granulocyte-macrophage CSF, or IL-3, but not that stimulated by platelet-activating factor, immobilized IgG, or PMA. Lidocaine and its derivatives show novel immunomodulatory properties and are able to blunt eosinophil responses to cytokines in addition to their local anesthetic or antiarrhythmic properties. Thus, lidocaine and its derivatives may represent a new class of therapeutic agents to treat patients with allergic diseases.


Heat-Treatment-Responsive Proteins in Different Developmental Stages of Tomato Pollen Detected by Targeted Mass Accuracy Precursor Alignment (tMAPA).
Recently, we have developed a quantitative shotgun proteomics strategy called mass accuracy precursor alignment (MAPA). The MAPA algorithm uses high mass accuracy to bin mass-to-charge (m/z) ratios of precursor ions from LC-MS analyses, determines their intensities, and extracts a quantitative sample versus m/z ratio data alignment matrix from a multitude of samples. Here, we introduce a novel feature of this algorithm that allows the extraction and alignment of proteotypic peptide precursor ions or any other target peptide from complex shotgun proteomics data for accurate quantification of unique proteins. This strategy circumvents the problem of confusing the quantification of proteins due to indistinguishable protein isoforms by a typical shotgun proteomics approach. We applied this strategy to a comparison of control and heat-treated tomato pollen grains at two developmental stages, post-meiotic and mature. Pollen is a temperature-sensitive tissue involved in the reproductive cycle of plants and plays a major role in fruit setting and yield. By LC-MS-based shotgun proteomics, we identified more than 2000 proteins in total for all different tissues. By applying the targeted MAPA data-processing strategy, 51 unique proteins were identified as heat-treatment-responsive protein candidates. The potential function of the identified candidates in a specific developmental stage is discussed.


Deactivation of implantable cardioverter-defibrillators: results of patient surveys.
The indications for implantable cardioverter-defibrillators (ICDs) have been expanding, especially for primary prevention of sudden cardiac death. Implantable cardioverter-defibrillator saves lives; however, in near end-of-life situations linked to incurable diseases, the question arises as to whether or not to turn off the ICD to avoid excessive numbers of shocks as the heart begins to fail. This study examined the wishes of a cohort of ICD recipients. Consecutive recipients of ICDs for primary or secondary prevention of sudden cardiac death were examined during a routine out-patient follow-up visit. Subjects completed a written survey about expected ICD benefits, feelings and circumstances under which they would want to deactivate the device. One hundred and nine patients fully completed the survey. Mean age was 67.6 ± 8.7 years, 91 (83.5%) were male and the mean systolic ejection fraction was 31.5 ± 10.9%. The severity of symptoms of heart failure according to the New York Heart Association classification was 2.1 ± 0.59 at implantation. Ninety-nine (90.8%) patients felt more secure and safe following ICD implantation and 66 (60.6%) patients reported a sense of improved health status after implantation. Thirty-one (28.4%) patients had experienced an ICD shock. Fifty (45.9%) patients indicated that they had never considered ICD deactivation during near end-of-life situations. This topic had been discussed with only eight (7.3%) patients. Forty-four (40.1%) patients wanted more information about ICD deactivation. On the other hand, 10 (41.7%) patients from secondary prevention and 19 (22.4%) from primary prevention groups categorically refused more information or further discussion on this topic (P = 0.058). Most ICD recipients felt safer following ICD implantation and most wanted more information regarding ICD deactivation. However, a significant number of patients (especially, secondary prevention patients) had no interest in receiving additional information about this topic.


Characterizing patients with multiple chromosomal aberrations detected by FISH in chronic lymphocytic leukemia.
We analyzed the features of chronic lymphocytic leukemia (CLL) with multiple abnormalities (MA) detected by FISH. A local database including 2095 CLL cases was used and 323 with MA (15.4%) were selected. MA was defined by the presence of two or more alterations (deletions of 13q14 (13q-), 11q22 (11q-), 17p13 (17p-) or trisomy 12 (+12)). The combination of 13q- with 11q- and 13q- with 17p-, accounted for 58.2% of the series, in contrast to 11q- with 17p- (3.7%). Patients carrying MA since diagnosis presented a short time to first therapy(TTFT) (27 months) and overall survival (OS) (76 months). The combinations including 17p- had a shorter OS (58 months) than the ones without 17p- (not reached, p = .002). Patients with a complex-FISH were the ones with worse OS (34 months). MA imply poor prognosis when they emerge at diagnosis, probably due to the high incidence of bad prognosis markers, which may be a reflection of a more complex karyotype.


A progressive and complex clinical course in two family members with ERF-related craniosynostosis: a case report.
ERF-related craniosynostosis are a rare, complex, premature trisutural fusion associated with a broad spectrum of clinical features and heterogeneous aetiology. Here we describe two cases with the same pathogenic variant and a detailed description of their clinical course. Two subjects; a boy with a BLSS requiring repeated skull expansions and his mother who had been operated once for sagittal synostosis. Both developed intracranial hypertension at some point during the course, which was for both verified by formal invasive intracranial pressure monitoring. Exome sequencing revealed a pathogenic truncating frame shift variant in the ERF gene. Here we describe a boy and his mother with different craniosynostosis patterns, but both with verified intracranial hypertension and heterozygosity for a truncating variant of ERF c.1201_1202delAA (p.Lys401Glufs*10). Our work provides supplementary evidence in support of previous phenotypic descriptions of ERF-related craniosynostosis, particularly late presentation, an evolving synostotic pattern and variable expressivity even among affected family members.


The impact of patient-reported outcome data from clinical trials: perspectives from international stakeholders.
Patient-reported outcomes (PROs) are increasingly collected in clinical trials as they provide unique information on the physical, functional and psychological impact of a treatment from the patient's perspective. Recent research suggests that PRO trial data have the potential to inform shared decision-making, support pharmaceutical labelling claims and influence healthcare policy and practice. However, there remains limited evidence regarding the actual impact associated with PRO trial data and how to maximise PRO impact to benefit patients and society. Thus, our objective was to qualitatively explore international stakeholders' perspectives surrounding: a) the impact of PRO trial data, b) impact measurement metrics, and c) barriers and facilitators to effectively maximise the impact of PRO trial data upon patients and society. Semi-structured interviews with 24 international stakeholders were conducted between May and October 2018. Data were coded and analysed using reflexive thematic analysis. International stakeholders emphasised the impact of PRO trial data to benefit patients and society. Influence on policy-impact, including changes to clinical healthcare practice and guidelines, drug approval and promotional labelling claims were common types of PRO impact reported by interviewees. Interviewees suggested impact measurement metrics including: number of pharmaceutical labelling claims and interviews with healthcare practitioners to determine whether PRO data were incorporated in clinical decision-making. Key facilitators to PRO impact highlighted by stakeholders included: standardisation of PRO tools; consideration of health utilities when selecting PRO measures; adequate funding to support PRO research; improved reporting and dissemination of PRO trial data by key opinion leaders and patients; and development of legal enforcement of the collection of PRO data. Determining the impact of PRO trial data is essential to better allocate funds, minimise research waste and to help maximise the impact of these data for patients and society. However, measuring the impact of PRO trial data through metrics is a challenging task, as current measures do not capture the total impact of PRO research. Broader international multi-stakeholder engagement and collaboration is needed to standardise PRO assessment and maximise the impact of PRO trial data to benefit patients and society.


Liposomes as chaperone mimics with controllable affinity toward heat-denatured formate dehydrogenase from Candida boidinii.
Chaperone machinery in living systems can catch denatured enzymes and induce their reactivation. Chaperone mimics are beneficial for applying enzymatic reactions in vitro. In this work, the affinity between liposomes and thermally denatured enzymes was controlled to stabilize the enzyme activity. The model enzyme is formate dehydrogenase from Candida boidinii (CbFDH) which is a homodimer and negatively charged in the phosphate buffer solution (pH 7.2) used. The activity of free CbFDH readily decreased at 58 °C following the first-order kinetics with the half-life t1/2 of 27 min. The turbidity measurements showed that the denatured enzyme molecules formed aggregates. The liposomes composed of zwitterionic phosphatidylcholines (PCs) stabilized the CbFDH activity at 58 °C, as revealed with six different PCs. The PC liposomes were indicated to bind to the aggregate-prone enzyme molecules, allowing reactivation at 25 °C. The cofactor β-reduced nicotinamide adenine dinucleotide (NADH) also stabilized the enzyme activity. The affinity between liposomes and denatured CbFDH could be modulated by incorporating cationic 1,2-dioleoyloxy-3-trimethylammonium propane chloride (DOTAP) in PC membranes. The t1/2 values significantly increased in the presence of liposomes ([lipid] = 1.5 mM) composed of PC and DOTAP at the mole fraction f(D) of 0.1. On the other hand, the DOTAP-rich liposomes (f(D) ≥ 0.7) showed strong affinity toward denatured CbFDH, accelerating its deactivation. The liposomes with low charge density function as chaperone mimics that can efficiently catch the denatured enzymes without interfering with their intramolecular interaction for reactivation.


[Chemical safety (1): The origin of the problem].
The genesis of the vast problem--of cognitive and applicatory nature--referred to as chemical safety, has been presented. Chemical safety studies involve all possible sources of man's exposure to chemical compounds, which is aimed at an effective control of adverse health effects. The authors have set up a definition according to which chemical safety occurs where exposure to chemical compounds coming from various sources causes a specific health risk not higher than the socially accepted level. The contribution of Poland to the International Program of Chemical Safety (IPCS) should promote the exchange of experiences and access to scientific and technological information.


Teaching the use of walkers and canes.
Home care and hospice nurses frequently encounter patients who use assistive devices to safely remain mobile in their homes. Incorrectly used, these devices may contribute to falls. This article provides a review on the use and teaching of these devices to patients and caregivers. A physical therapist, occupational therapist, or rehabilitation nurse should be consulted for any questions about applying the guidelines in this article to patients.


Nanoscale uniform self-assembled monolayers of fluorescent zinc(II) complexes on the Si(100) surface.
The synthesis of self-assembled monolayers on Si(100) substrates of a new fluorescent Zn(II) Schiff-base complex is reported. Chemisorbed species are characterized by the combination of fluorescence scanning near-field optical/atomic force microscopy (SNOM/AFM), and by fluorescence spectroscopy. Both SNOM/AFM results indicate the existence of a monolayer on the surface, while optical SNOM images highlight the contribution of the monolayer to the local fluorescence. While chemisorbed molecular monolayers exhibit a distinct fluorescence, analogous to that observed in solution, cast thin films do not show any emission. Photoluminescent properties of the monolayer can be related to its nanoscale uniform, ordered structure.


Satisficing in split-second decision making is characterized by strategic cue discounting.
Much of our real-life decision making is bounded by uncertain information, limitations in cognitive resources, and a lack of time to allocate to the decision process. It is thought that humans overcome these limitations through satisficing, fast but "good-enough" heuristic decision making that prioritizes some sources of information (cues) while ignoring others. However, the decision-making strategies we adopt under uncertainty and time pressure, for example during emergencies that demand split-second choices, are presently unknown. To characterize these decision strategies quantitatively, the present study examined how people solve a novel multicue probabilistic classification task under varying time pressure, by tracking shifts in decision strategies using variational Bayesian inference. We found that under low time pressure, participants correctly weighted and integrated all available cues to arrive at near-optimal decisions. With increasingly demanding, subsecond time pressures, however, participants systematically discounted a subset of the cue information by dropping the least informative cue(s) from their decision making process. Thus, the human cognitive apparatus copes with uncertainty and severe time pressure by adopting a "drop-the-worst" cue decision making strategy that minimizes cognitive time and effort investment while preserving the consideration of the most diagnostic cue information, thus maintaining "good-enough" accuracy. This advance in our understanding of satisficing strategies could form the basis of predicting human choices in high time pressure scenarios. (PsycINFO Database Record


A review of cardiovascular risk factors in US military personnel.
As the civilian population exhibits increasing trends in major cardiovascular (CV) risk factors in younger age groups, the US military is observing similar trends. These worrisome developments are seen even in young adulthood. Despite the need for a fit, combat-ready force, increases in CV risk are increasingly evident in the military population. This review provides an overview of coronary artery disease in the young and the prevalence of risk factors in the military population. With increases in current military operations in an acutely stressful environment, the role of stress and the manifestation of CV disease are also examined.


Direct Mg(2+) binding activates adenylate kinase from Escherichia coli.
We report evidence that adenylate kinase (AK) from Escherichia coli can be activated by the direct binding of a magnesium ion to the enzyme, in addition to ATP-complexed Mg(2+). By systematically varying the concentrations of AMP, ATP, and magnesium in kinetic experiments, we found that the apparent substrate inhibition of AK, formerly attributed to AMP, was suppressed at low magnesium concentrations and enhanced at high magnesium concentrations. This previously unreported magnesium dependence can be accounted for by a modified random bi-bi model in which Mg(2+) can bind to AK directly prior to AMP binding. A new kinetic model is proposed to replace the conventional random bi-bi mechanism with substrate inhibition and is able to describe the kinetic data over a physiologically relevant range of magnesium concentrations. According to this model, the magnesium-activated AK exhibits a 23- +/- 3-fold increase in its forward reaction rate compared with the unactivated form. The findings imply that Mg(2+) could be an important affecter in the energy signaling network in cells.


The benefits of integrating a statistician into a nursing research department.
In today's competitive healthcare market, more hospitals are seeking Magnet® designation. To meet the expectations for evidence-based practice and research, many organizations are considering the addition of statistical expertise to their team. The authors discuss the benefits of analytical support and integration of a statistician on the team.


Activity of Pseudomonas aeruginosa in biofilms: effect of calcium.
Aerobic glucose metabolism by Pseudomonas aeruginosa biofilms at various calcium loading rates was investigated. The influence of calcium on specific growth rate, extracellular polymeric substance (EPS) formation rate, biofilm detachment rate, and biofilm calcium concentrations was determined. Calcium accumulated in the biofilm in proportion to the liquid phase concentration. Increasing calcium concentration increased the cohesiveness of the biofilm as indicated by a lower relative detachment rate. Specific activity in the biofilm was the same as that measured in a chemostat and was not influenced by changing calcium concentration. EPS formation rate in the biofilm was unaffected by calcium concentration but was higher than that observed in a chemostat.


Population-based survival from cancers having a poor prognosis in Mumbai (Bombay), India.
Oesophagus, stomach, pancreas and lung cancers contribute more than 35% of the total cancer incidence in Mumbai and survival rates for these cancers are very poor in most populations in the world. The authors here report and discuss the population-based survival from these cancers in Mumbai, India. Follow-up information on 5717 cancers patients having a low prognosis, registered in the Mumbai Population-Based Cancer Registry for the period 1987-1991, was obtained by a variety of methods, including matching with death certificates from the Mumbai vital statistics registration system, postal/telephone enquiries, home visits and scrutiny of medical records. The survival for each case was determined as the duration between the date of diagnosis and date of death, loss to follow-up or the closing date of the study at the end of 1996. Cumulative observed and relative survival rates were calculated by the Hakulinen Method. For comparison of results with other populations, age-standardized relative survival (ASRS) was calculated by directly standardizing age specific relative survival to the specific age distributions of the estimated global incidence of major cancers in 1985. The log rank test was used with univariate analysis to identify the potentially important prognostic variables. The variables showing statistical significance in univariate analysis were introduced stepwise into a Cox Regression model to identify the independent predictors of survival. The 5-year relative survival rates were 11.8% for oesophagus, 10.1% for the stomach, 4.1% for the pancreas, and 7.0% for lung. Females had higher survival rates than males, except with lung cancer. Lower survival was observed for those younger than 35 years for all 4 sites. For each site, survival declined with advancing age. Single patients who remained unmarried had better survival, except with pancreatic cancer. For all sites Muslims had a better survival and Christians had a lower survival as compared to Hindus. Education did not show any pattern for any site. Survival decreased rapidly with advancing clinical extent of disease for all sites. Survival for localized cancer ranged from 12.5% to 31.3%, for regional spread 1.3% to 3.4% and with distant metastasis not a single site recorded more than 1%. On multivariate analysis, extent of disease emerged as an independent predictor of survival with all the sites. Also, age for oesophagus, stomach and lung, religion for oesophagus and stomach, and education for stomach and lung, emerged as independent predictors of survival. All the sites included in the study demonstrated very low survival rates with significant variation. Comparison with other populations revealed lower survival rates than for Shanghai-China. In remaining populations, survival proportions did not show much variation for pancreas and lung cancers. For stomach cancer, European countries showed better survival rates. Early detection with treatment is clearly important to reduce the mortality from these cancers.


[Contribution of the mechanocardiography to the study of obstructive chronic bronchopneumopathy].
Kinetocardiography, ECG and radiography, were compared as ways of obtaining early diagnosis of chronic cor pulmonale in two series of patients (81 in all) with chronic obstructive bronchopneumopathy. Kinetocardiography proved markedly superior in this respect. It revealed right ventricular pressure overload in a higher percentage of cases and at an earlier stage, i.e. when PAP values were little above normal resting values, of even when their increase appeared only during physical effort.


A Vaginal Tract Signal Detected by the Group B Streptococcus SaeRS System Elicits Transcriptomic Changes and Enhances Murine Colonization.
Streptococcus agalactiae (group B streptococcus [GBS]) can colonize the human vaginal tract, leading to both superficial and serious infections in adults and neonates. To study bacterial colonization of the reproductive tract in a mammalian system, we employed a murine vaginal carriage model. Using transcriptome sequencing (RNA-Seq), the transcriptome of GBS growing in vivo during vaginal carriage was determined. Over one-quarter of the genes in GBS were found to be differentially regulated during in vivo colonization compared to laboratory cultures. A two-component system (TCS) homologous to the staphylococcal virulence regulator SaeRS was identified as being upregulated in vivo One of the SaeRS targets, pbsP, a proposed GBS vaccine candidate, is shown to be important for colonization of the vaginal tract. A component of vaginal lavage fluid acts as a signal to turn on pbsP expression via SaeRS. These data demonstrate the ability to quantify RNA expression directly from the murine vaginal tract and identify novel genes involved in vaginal colonization by GBS. They also provide more information about the regulation of an important virulence and colonization factor of GBS, pbsP, by the TCS SaeRS.


Adipocyte-Specific Deletion of Manganese Superoxide Dismutase Protects From Diet-Induced Obesity Through Increased Mitochondrial Uncoupling and Biogenesis.
Obesity and insulin resistance are associated with oxidative stress (OS). The causal role of adipose OS in the pathogenesis of these conditions is unknown. To address this issue, we generated mice with an adipocyte-selective deletion of manganese superoxide dismutase (MnSOD). When fed a high-fat diet (HFD), the AdSod2 knockout (KO) mice exhibited less adiposity, reduced adipocyte hypertrophy, and decreased circulating leptin. The resistance to diet-induced adiposity was the result of an increased metabolic rate and energy expenditure. Furthermore, palmitate oxidation was elevated in the white adipose tissue (WAT) and brown adipose tissue of AdSod2 KO mice fed an HFD, and the expression of key fatty acid oxidation genes was increased. To gain mechanistic insight into the increased fat oxidation in HFD-fed AdSod2 KO mice, we quantified the mitochondrial function and mitochondrial content in WAT and found that MnSOD deletion increased mitochondrial oxygen consumption and induced mitochondrial biogenesis. This effect was preserved in cultured adipocytes from AdSod2 KO mice in vitro. As expected from the enhanced fat oxidation, circulating levels of free fatty acids were reduced in the HFD-fed AdSod2 KO mice. Finally, HFD-fed AdSod2 KO mice were protected from hepatic steatosis, adipose tissue inflammation, and glucose and insulin intolerance. Taken together, these results demonstrate that MnSOD deletion in adipocytes triggered an adaptive stress response that activated mitochondrial biogenesis and enhanced mitochondrial fatty acid oxidation, thereby preventing diet-induced obesity and insulin resistance.


Effects of physical training programs on female tennis players' performance: a systematic review and meta-analysis.
Background: Tennis is among the world's most popular and well-studied sports. Physical training has commonly been used as an intervention among athletes. However, a comprehensive review of the literature on the effects of physical training programs on female tennis players' performance is lacking. Therefore, this systematic review and meta-analysis aimed to determine the effects of physical training on performance outcomes in female tennis players. Methods: A comprehensive search was conducted on Web of Science, PubMed, SPORTDicus, Scopus, and CNKI from inception until July 2023 to select relevant articles from the accessible literature. Only controlled trials were included if they examined the effects of physical training on at least one measure of tennis-specific performance in female tennis players. The Cochrane RoB tool was employed to assess the risk of bias. The CERT scale was used to examine the quality of program information. The GRADE approach was adopted to evaluate the overall quality of the evidence. The Comprehensive Meta-Analysis software was used for the meta-analysis. Results: Nine studies were selected for the systematic review and seven for the meta-analysis, totaling 222 individuals. The study's exercise programs lasted 6-36 weeks, with training sessions ranging from 30 to 80 min, conducted one to five times per week. Muscle power (ES = 0.72; p = 0.003), muscle strength (ES = 0.65; p = 0.002), agility (ES = 0.69; p = 0.002), serve velocity (ES = 0.72; p = 0.013), and serve accuracy (ES = 1.14; p = 0.002) demonstrated significant improvement following physical training, while no notable changes in linear sprint speed (ES = 0.63; p = 0.07) were detected. Conclusion: Although research on physical training in sports is diversified, studies on training interventions among female tennis players are scarce. This review found that existing training programs yield some favorable outcomes for female tennis players. However, further research with high methodological quality is warranted on the tailoring of specific training programs for female tennis players. There should be more consistent measuring and reporting of data to facilitate meaningful data pooling for future meta-analyses.


Anomalous Charge Transfer from Organic Ligands to Metal Halides in Zero-Dimensional [(C6 H5 )4 P]2 SbCl5 Enabled by Pressure-Induced Lone Pair-π Interaction.
Low-dimensional (low-D) organic metal halide hybrids (OMHHs) have emerged as fascinating candidates for optoelectronics due to their integrated properties from both organic and inorganic components. However, for most of low-D OMHHs, especially the zero-D (0D) compounds, the inferior electronic coupling between organic ligands and inorganic metal halides prevents efficient charge transfer at the hybrid interfaces and thus limits their further tunability of optical and electronic properties. Here, using pressure to regulate the interfacial interactions, efficient charge transfer from organic ligands to metal halides is achieved, which leads to a near-unity photoluminescence quantum yield (PLQY) at around 6.0 GPa in a 0D OMHH, [(C6 H5 )4 P]2 SbCl5 . In situ experimental characterizations and theoretical simulations reveal that the pressure-induced electronic coupling between the lone-pair electrons of Sb3+ and the π electrons of benzene ring (lp-π interaction) serves as an unexpected "bridge" for the charge transfer. Our work opens a versatile strategy for the new materials design by manipulating the lp-π interactions in organic-inorganic hybrid systems.


Plasmid presence changes the relative levels of many host cell proteins and ribosome components in recombinant Escherichia coli.
Relative levels of many individual proteins in Escherichia coli HB101 strains with 0, 37, 56, and 240 plasmids per chromosome were determined by computer image analysis of two-dimensional gel electrophoresis patterns. The plasmids investigated had very similar sequences except for small domains encoding the repressor of plasmid replication. At the intermediate plasmid copy number of 56, levels of several of the TCA cycle enzymes (oxoglutarate dehydrogenase complex, succinate thiokinase, and succinate dehydrogenase) as well as in aspartate transcarbamoylase increased. At a plasmid copy number of 240, higher amounts of PEP carboxylase as well as several of the heat shock proteins were observed. Furthermore, at high plasmid levels, significant decreases occurred in growth rate, pyruvate kinase I, pyruvate dehydrogenase complex, unadenylated glutamine synthetase, aspartate transcarbamoylase as well as in several of the proteins involved in translation. Decreases in ribosome content as well as in the free 30S and 50S ribosomal subunit pool fractions were also observed in separate analyses. These results indicate that recombinant DNA manipulations can cause major alterations in numerous host cell properties which could significantly influence cloned protein production or metabolic engineering endeavors.