Is vaccination with quadrivalent HPV vaccine after loop electrosurgical excision procedure effective in preventing recurrence in patients with high-grade cervical intraepithelial neoplasia (CIN2-3)?
This study was conducted to determine whether vaccination with the quadrivalent human papillomavirus (HPV) vaccine after loop electrosurgical excision procedure (LEEP) for high-grade cervical intraepithelial neoplasia (CIN2-3) is effective in preventing recurrence of CIN2-3. Between August 2007 and July 2010, 737 patients aged 20-45 years who were diagnosed with CIN2-3 were treated by LEEP and followed. Three hundred and sixty patients were vaccinated with the quadrivalent HPV vaccine after LEEP (vaccination group), and 377 patients were followed without vaccination (non-vaccination group). The vaccination group received the first dose at 1 week after LEEP and the remaining two doses two and six months later. Post-LEEP follow-up was performed at 3, 6, 9, 12, 18, and 24 months during the first 2 years and yearly thereafter. Irrespective of causal HPV type, 36 (4.9%) patients developed recurrence. In the vaccination group (360 patients), 9 patients (2.5%) developed recurrence, whereas 27 patients (7.2%) in the non-vaccination group (377 patients) developed recurrence. In patients infected with HPV of 16 and/or 18 type, 5 patients (2.5%) in the vaccination group (197 patients) and 18 patients (8.5%) in the non-vaccination group (211 patients) developed recurrent disease related to vaccine HPV types (HPV 16 or 18 types) after LEEP (P<0.01). Multivariate analysis showed that no vaccination after LEEP was an independent risk factor for recurrent CIN2-3 (HR=2.840; 95% confidence interval, 1.335-6.042; P<0.01). Vaccination with the quadrivalent HPV vaccine after treatment may be considered in preventing recurrence of CIN2-3.


Surgical indications for infantile subdural effusion.
Thirty-four cases of infantile subdural effusion (ISE) were reviewed in relation to surgical treatment and its prognosis during an average of 4 years of extended follow-up. The surgical indications were determined mainly by the size of the ISE on computed tomography (CT) scan and by metrizamide CT cisternography (MCTC). Consequently, 18 cases were categorized as type A according to MCTC, including 11 cases (61.1%) of ISE CT grade 1. All type A cases were closely observed. This nontreatment regimen yielded excellent results in 15 cases (83.3%). For 10 cases categorized as type B according to MCTC, including 5 cases (50%) of ISE CT grade 3, surgical treatment was indicated and excellent results were obtained in 8 cases (80%). For 6 cases categorized as type C according to MCTC and as ISE CT grade 3, surgery yielded excellent results in 4 cases (66.7%). Antiepileptic drugs have been given to three (27.3%) of the 11 patients who had convulsive attacks. In conclusion, the surgical indications for ISE were based mainly on MCTC in addition to the clinical course, and it is emphasized that, in the early stages, surgery on ISE cases categorized as MCTC types B and C is necessary.


Pathways between lymph vessels and sinuses in lymph nodes: a study in horses.
The pathways through which lymph flows from terminal afferent lymphatics to the lymph sinuses, and from the sinuses to initial efferent lymphatics, were studied in horse lymph nodes by using Microfil casts and electron microscopy. Terminal afferent lymphatics are continuous with the subcapsular sinus through oval holes, about 3 microns wide, along their length, and through larger openings near their end. Other terminal afferents penetrate into the node within trabeculae and are supported by processes across the lumen. They connect with trabecular and medullary sinuses through oval or round holes, generally 20-30 microns across. Some of these have processes, similar to the luminal strands of the adjacent sinuses, extending across them, apparently providing reinforcement. Initial efferent lymphatics receive lymph from medullary sinuses through holes which are similar to those in afferent lymphatics, though more common, especially near the origin of the vessel. Initial efferents within the medulla appear to be supported by the luminal strands of the surrounding medullary sinuses. It seems likely that these strands, like the trabeculae which surround the penetrating afferent lymphatics, may help to keep the lymphatic vessels open as the node swells while draining an area of infection.


Frequency and patterns of protease gene resistance mutations in HIV-infected patients treated with lopinavir/ritonavir as their first protease inhibitor.
Selection of protease mutations on antiretroviral therapy (ART) including a ritonavir-boosted protease inhibitor (PI) has been reported infrequently. Scarce data exist from long-term cohorts on resistance incidence or mutational patterns emerging to different PIs. We studied UK patients receiving lopinavir/ritonavir as their first PI, either while naive to ART or having previously received non-PI-based ART. Virological failure was defined as viral load ≥ 400 copies/mL after previous suppression <400 copies/mL, or failure to achieve <400 copies/mL during the first 6 months. pol sequences whilst failing lopinavir or within 30 days after stopping were analysed. Major and minor mutations (IAS-USA 2008-after exclusion of polymorphisms) were considered. Predicted susceptibility was determined using the Stanford HIVdb algorithm. Three thousand and fifty-six patients were followed for a median (IQR) of 14 (6-30) months, of whom 811 (27%) experienced virological failure. Of these, resistance test results were available on 291 (36%). One or more protease mutations were detected in 32 (11%) patients; the most frequent were I54V (n = 12), M46I (n = 11), V82A (n = 7) and L76V (n = 3). No association with viral subtype was evident. Many patients retained virus predicted to be susceptible to lopinavir (14, 44%), tipranavir (26, 81%) and darunavir (27, 84%). This study reflects the experience of patients in routine care. Selection of protease gene mutations by lopinavir/ritonavir occurred at a much higher rate than in clinical trials. The mutations observed showed only partial overlap with those previously identified by structural chemistry models, serial cell culture passage and genotype-phenotype analyses. There remained a low degree of predicted cross-resistance to other widely used PIs.


Progesterone and progestins: neuroprotection and myelin repair.
Progesterone, known for its role in pregnancy, also exerts marked effects on the nervous system. Its neuroprotective and promyelinating actions, now well documented by experimental studies, make it a particularly promising therapeutic agent for neuroinjury and neurodegenerative diseases. This concept has recently been translated into clinical practice, though there is need for more experimental studies and investigations on the mechanisms of the actions of progesterone. However, it is important to be aware that most of the experimental research concerns the effects of physiological progesterone. Although progesterone represents an interesting therapeutic option, the recognition of its beneficial effects on the nervous system also suggests novel therapeutic benefits for some synthetic progestins derived from progesterone, currently used for contraception or in postmenopausal hormone replacement therapies (HRTs).


Applications of quaternary ammonium compounds in the prevention and treatment of oral diseases: State-of-the-art and future directions.
The aim of this review is to comprehensively summarize the state-of-the-art developments of quaternary ammonium compounds (QACs) in the prevention and treatment of oral diseases. By discussing the structural diversity and the potential killing mechanism, we try to offer some insights for the future research of QACs. A literature search was conducted in electronic databases (Web of Science, PubMed, Medline, and Scopus). Publications that involved the applications of QACs, especially those related to the prevention and treatment of oral diseases, are included. We have reviewed the relevant research on QACs over the past two decades. The research results indicate that the current applications are mainly focused on dental material modification and direct pharmacological interventions. Concurrently, challenges such as potential risks to normal tissues and impediments in drug resistance and microbial persistence present certain application constraints. The latest studies have encompassed the exploration of smart materials and nanoparticle formulations. The killing mechanism may possess a threshold related to charge density. However, the exact process remains enigmatic. The structural diversity and the exploration of intelligent materials and nanoparticle formulations provide directions in development of novel QACs. The intricate oral anatomy, combined with the multifaceted oral microbiome, necessitates specialized materials for the targeted prevention and treatment of oral pathologies. QACs represent a cohort of compounds distinguished by potent anti-infective and anti-tumor attributes. Innovations in intelligent materials and nanoparticle formulations amplify their potential in significantly advancing the prevention and therapeutic interventions for oral diseases.


DNA/RNA binding and anticancer/antimicrobial activities of polymer-copper(II) complexes.
Water soluble polymer-copper(II) complexes with various degrees of coordination in the polymer chain were synthesized and characterized by elemental analysis, IR, UV-visible and EPR spectra. The DNA/RNA binding behavior of these polymer-copper(II) complexes was examined by UV-visible absorption, emission and circular dichroism spectroscopic methods, and cyclic voltammetry techniques. The binding of the polymer-copper(II) complexes with DNA/RNA was mainly through intercalation but some amount of electrostatic interaction was also observed. This binding capacity increased with the degree of coordination of the complexes. The polymer-copper(II) complex having the highest degree of coordination was subjected to analysis of cytotoxic and antimicrobial properties. The cytotoxicity study indicated that the polymer-copper(II) complexes affected the viability of MCF-7 mammary carcinoma cells, and the cells responded to the treatment with mostly through apoptosis although a few cells succumbed to necrosis. The antimicrobial screening showed activity against some human pathogens.


Workplace factors can predict the stress levels of healthcare workers during the COVID-19 pandemic: First interim results of a multicenter follow-up study.
Research is lacking on the long-term influence of workplace factors on the mental health of health care workers during the COVID-19 pandemic. We distributed two online surveys to health care workers between May and October 2020 (T1) and between February and April 2021 (T2). Perceived stress, coronavirus-related risks, and workplace factors were measured via self-report questionnaires at both time points. We conducted hierarchical linear regression to investigate the predictive factors for high stress. A total of 2,110 participants from seven countries and 4,240 participants from nine countries were enrolled at T1 and T2, respectively. Among them, 612 participated in both surveys. We called this cohort T1 + T2. High stress was reported in 53.8 and 61.6% of participants at T1 and T2, respectively. In cohort T1 + T2, compared with the baseline, the level of stress rose significantly (6.0 ± 2.9 vs. 6.4 ± 3.1), as did health/safety in the workplace (3.9 ± 0.8 vs. 4.2 ± 0.7). Unfortunately, we did not detect any significant difference concerning support in the workplace. Among all factors at baseline, being older than 35 [β (95% CI) = -0.92 (-1.45, -0.40)], support [-0.80 (-1.29, -0.32)], and health/safety in the workplace [-0.33 (-0.65, -0.01)] were independent protective factors, while a positive history of mental disorders [0.81 (0.26, 1.37)] and rejection in private life [0.86 (0.48, 1.25)] were risk factors for high stress at T2. To relieve the high stress of health care workers, organizational-level approaches should be implemented, especially measures designed to enhance support, health/safety in the workplace, and to reduce the rejection of the public.


Pediatric malpractice: an overview of Turkey.
The objective of this study was to evaluate juridical and medical responsibilities of health-care professionals accused of malpractice in Turkey while they care for patients under the age of 18. The cases sent to the Council of Forensic Medicine Institution by the courts, including claims of medical malpractice (n = 1458), in order to get an expert opinion between 2002 and 2006, were examined retrospectively. Cases of negligence by health-care professionals who gave medical care to children between the ages of 0 and 18 were evaluated statistically. There was medical malpractice in 28.8% of the cases; and 68.2% of the cases were male. A large proportion of the cases were found to occur in emergency departments; and 57.9% of injuries resulted in death. The specialist doctors seemed to be sued or to be accountable for compensation more frequently than the general practitioners. This can be attributed to the fact that they perform more complicated medical interventions. Courts specializing in health legislation may be useful to decrease the time consumed by trials. These specialized courts will also support logical judgment. In addition, postgraduate education is useful in reducing malpractice claims.


A rare missense mutation in CHRNA4 associates with smoking behavior and its consequences.
Using Icelandic whole-genome sequence data and an imputation approach we searched for rare sequence variants in CHRNA4 and tested them for association with nicotine dependence. We show that carriers of a rare missense variant (allele frequency=0.24%) within CHRNA4, encoding an R336C substitution, have greater risk of nicotine addiction than non-carriers as assessed by the Fagerstrom Test for Nicotine Dependence (P=1.2 × 10(-4)). The variant also confers risk of several serious smoking-related diseases previously shown to be associated with the D398N substitution in CHRNA5. We observed odds ratios (ORs) of 1.7-2.3 for lung cancer (LC; P=4.0 × 10(-4)), chronic obstructive pulmonary disease (COPD; P=9.3 × 10(-4)), peripheral artery disease (PAD; P=0.090) and abdominal aortic aneurysms (AAAs; P=0.12), and the variant associates strongly with the early-onset forms of LC (OR=4.49, P=2.2 × 10(-4)), COPD (OR=3.22, P=2.9 × 10(-4)), PAD (OR=3.47, P=9.2 × 10(-3)) and AAA (OR=6.44, P=6.3 × 10(-3)). Joint analysis of the four smoking-related diseases reveals significant association (P=6.8 × 10(-5)), particularly for early-onset cases (P=2.1 × 10(-7)). Our results are in agreement with functional studies showing that the human α4β2 isoform of the channel containing R336C has less sensitivity for its agonists than the wild-type form following nicotine incubation.


Ten patients with refractory status epilepticus in an intensive care department.
Status epilepticus (SE) is a serious disease, associated with a high morbidity and mortality, particularly if refractory to initial therapy. We describe the clinical manifestations and outcome in ten cases with refractory SE admitted to our medical intensive care unit. Three of these selected group of cases with SE had pre-existent epilepsia. Of the seven patients with new-onset epilepsia, six had multiple underlying systemic diseases. The three patients with pre-existent epilepsia had a favourable outcome of their SE. However, in the seven patients without known structural and/or functional cerebral defects SE was also refractory to second or third line therapy. Administration of thiopental suppressed epileptic activity only temporarily. None of them survived due to coexistent pathology and the onset of secondary metabolic complications. Thus, especially cases with new-onset epilepsia debuting as refractory SE in the presence of underlying systemic diseases had a fatal outcome in our medical intensive care unit.


Iterative image reconstruction algorithms using wave-front intensity and phase variation.
Iterative algorithms that reconstruct images from far-field x-ray diffraction data are plagued with convergence difficulties. An iterative image reconstruction algorithm is described that ameliorates these convergence difficulties through the use of diffraction data obtained with illumination modulated in both intensity and phase.


Material gradients in gastropod radulae and their biomechanical significance: a combined approach on the paludomid Lavigeria grandis.
The radula, a chitinous membrane spiked with teeth, is the molluscan autapomorphy for the gathering and processing of food. The teeth, as actual interfaces between the organism and the ingesta, act as load transmitting regions and have to withstand high stresses during foraging - without structural failure or high degrees of wear. Mechanisms contributing to this were studied previously in paludomid gastropods from Lake Tanganyika. For some species, gradients in hardness and Young's modulus along the teeth were detected, enabling the bending and relying of teeth onto the next row, distributing the stresses more equally. The here presented study on one of them - Lavigeria grandis - aims at shedding light on the origin of these functional gradients. The mechanical properties were identified by nanoindentation technique and compared to the elemental composition, determined by elemental dispersive X-ray spectroscopy (EDX, EDS). This was done for the complete radular (mature and immature tooth rows), resulting in overall 236 EDX and 700 nanoindentation measurements. Even though teeth showed regional differences in elemental composition, we could not correlate the mechanical gradients with the elemental proportions. By applying confocal laser scanning microscopy (CLSM), we were finally able to relate the mechanical properties with the degree of tanning. CLSM is a common technique used on arthropod cuticle, but was never applied on radular teeth before. In general, we found that nanoindentation and CLSM techniques complement one another, as for example, CLSM is capable of revealing heterogeneities in material or micro-gradients, which leads to a better understanding of the functionalities of biological materials and structures.


MfERG waveform characteristics in the RS1h mouse model featuring a 'negative' ERG.
Several retinal disorders lead to a relatively greater attenuation of the b-wave compared to the a-wave of the electroretinogram (ERG), a constellation called 'negative' ERG. To determine the waveform characteristics of multifocal ERGs (mfERGs) and their dependence on recording parameters in such a case, we studied the Rs1h(-/Y) mouse, the model for x-linked juvenile retinoschisis. mfERGs were recorded with a VERIS 4 system connected to a piggyback stimulator prototype that added the stimulus to the optical pathway of a HRA scanning-laser ophthalmoscope (SLO) by means of a wavelength-sensitive mirror. Real-time fundus visualization was achieved with the infrared laser of the SLO (835 nm). High-pass filter settings and the time interval used by the 'artefact removal' feature were varied to study their influence on the waveform. The mfERG in the Rs1h(-/Y) mouse had a 'negative' shape. However, the high-pass filter setting had to be lowered from the usual 10 Hz down to about 2 Hz in order to obtain that result, otherwise the negative shape was lost and mainly a positive peak remained. Similarly, a short time interval used by the 'artefact removal' feature also removed the negative shape. The Rs1h(-/Y) mouse was found to be a valuable model of diseases with a 'negative' waveform shape also in mfERG. Our results underline the importance of a lower high-pass filter cutoff frequency when recording mfERGs in such disorders. In addition, if the 'artefact removal' feature is used, it should be verified that it doesn't distort the waveform shape.


American medical education at a crossroads.
New medical-education models in which research plays a modest role could engender a two-tiered educational system, cause a reduction in the physician-scientist pipeline, and diminish the translation of biomedical advances.


Functional identification of SLC43A3 as an equilibrative nucleobase transporter involved in purine salvage in mammals.
The purine salvage pathway plays a major role in the nucleotide production, relying on the supply of nucleobases and nucleosides from extracellular sources. Although specific transporters have been suggested to be involved in facilitating their transport across the plasma membrane in mammals, those which are specifically responsible for utilization of extracellular nucleobases remain unknown. Here we present the molecular and functional characterization of SLC43A3, an orphan transporter belonging to an amino acid transporter family, as a purine-selective nucleobase transporter. SLC43A3 was highly expressed in the liver, where it was localized to the sinusoidal membrane of hepatocytes, and the lung. In addition, SLC43A3 expressed in MDCKII cells mediated the uptake of purine nucleobases such as adenine, guanine, and hypoxanthine without requiring typical driving ions such as Na(+) and H(+), but it did not mediate the uptake of nucleosides. When SLC43A3 was expressed in APRT/HPRT1-deficient A9 cells, adenine uptake was found to be low. However, it was markedly enhanced by the introduction of SLC43A3 with APRT. In HeLa cells, knock-down of SLC43A3 markedly decreased adenine uptake. These data suggest that SLC43A3 is a facilitative and purine-selective nucleobase transporter that mediates the cellular uptake of extracellular purine nucleobases in cooperation with salvage enzymes.


Penicillium polonicum a new isolate obtained from Cerrado soil as a source of carbohydrate-active enzymes produced in response to sugarcane bagasse.
Penicillium species have been studied as producers of plant cell wall degrading enzymes to deconstruct agricultural residues and to be applied in industrial processes. Natural environments containing decaying plant matter are ideal places for isolating fungal strains with cellulolytic and xylanolytic activities. In the present study, Cerrado soil samples were used as source of filamentous fungi able to degrade xylan and cellulose. Penicillium was the most abundant genus among the obtained xylan and carboxymethylcellulose degraders. Penicillium polonicum was one of the best enzyme producers in agar-plate assays. In addition, it secretes CMCase, Avicelase, pectinase, mannanase, and xylanase during growth in liquid media containing sugarcane bagasse as carbon source. The highest value for endo-β-1,4-xylanase activity was obtained after 4 days of growth. Xyl PP, a 20 kDa endo-β-1,4-xylanase, was purified and partially characterized. The purified enzyme presented the remarkable feature of being resistant to the lignin-derived phenolic compounds, p-coumaric and trans-ferulic acids. This feature calls for its further use in bioprocesses that use lignocellulose as feedstock. Furthermore, future work should explore its structural features which may contribute to the understanding of the relationship between its structure and resistance to phenolic compounds. The online version contains supplementary material available at 10.1007/s13205-022-03405-x.


Consequences of using poly-ether-ether-ketone versus traditional implant on tibial cement penetration and short-term clinical outcomes during total knee arthroplasty: a randomized controlled trial.
The use of poly-ether-ether-ketone (PEEK) prosthesis during total knee arthroplasty (TKA) is a relatively new concept. Several studies have suggested that the thickness of cement penetration during TKA may affect the stability of the implants. The present study aimed to compare the cement penetration and clinical performance between PEEK and traditional cobalt chromium molybdenum (CoCrMo) prosthesis during TKA. This study was a randomized controlled trial with level I of evidence. A total of 48 patients were randomly assigned to either the PEEK group (n = 24) or the CoCrMo group (n = 24). Mean bone cement penetration under the tibial baseplate was assessed radiographically in four zones in the anteroposterior view and two zones in the lateral view, in accordance with the Knee Society Scoring System. Furthermore, parameters such as the Knee Society Score (KSS), visual analogue scale (VAS) scores, complications and survivorship at 1 year postoperatively were also compared. According to the results of this study, the mean bone cement penetration exhibited no significant difference between PEEK and CoCrMo groups (2.49 ± 0.61 mm vs. 2.53 ± 0.68 mm, p = 0.85). Additionally, there were no remarkable differences in the KSS clinical score, functional score, and VAS score between the two groups. Moreover, complications and survivorship were also statistically compared between the groups and presented no significant differences. Based on the current findings, it can be concluded that PEEK implant present similar bone cement penetration, short-term clinical outcomes, and survivorship with traditional CoCrMo implant in TKA without added complications. Trial registration Chinese Clinical Trial Registry (ChiCTR2100047563).


Rituximab as induction therapy in pediatric kidney transplantation: A single-center experience in four patients.
The anti-CD20 rituximab is often used in the treatment of children with steroid-resistant nephrotic syndrome or EBV-induced post-transplant lymphoproliferative disorder. This single-center series reports the use of rituximab as induction therapy in pediatric kidney transplantation. Four children who received rituximab as induction therapy for kidney transplantation since 2016 were retrospectively analyzed. Clinical and laboratory data were extracted from medical records. The patients (2 boys and 2 girls) were aged from 6.1 to 11.9 years and were treated with rituximab on the day of the transplantation procedure; all the transplants came from deceased donors. In all patients, rituximab was used because of positive EBV viral loads before kidney transplantation. Viral loads remained undetectable for the first 6 months after the transplantation procedure and remained below the 4.5 log threshold thereafter. After a median follow-up of 2.3 years, none of the patients displayed rejection or de novo donor-specific antibodies; the glomerular filtration rate remained above 70 ml/min/1.73 m2 . No post-transplant lymphoproliferative disorder was observed. The results suggest that rituximab can be used as induction therapy to prevent EBV replication and its complications in case of positive viral load prior to kidney transplantation.


Phenological variation in fruit characteristics in vertebrate-dispersed plants.
We investigated inter-specific variation in fruit characteristics - fruit size, seed number per fruit, seed weight, nutritional content, fruit persistence, and fruit synchronization - in relation to flowering and fruiting phenology in 34 species of fleshy fruited plants. Except for aspects of fruit synchrony and persistence, the results in general were inconsistent with previous suggestions about adaptive variation in phenologically related fruit traits. The main results were as follows: (1) Late flowering, late fruiting, lengthy development time from flower to fruit, and highly persistent fruits constitute a complex of correlated characteristics among the species. (2) Synchronization of fruiting within individuals increased from early ripening fruits to late ripening fruits. Fruiting synchrony was more pronounced in species with a small crop size than in species with a large fruit crop, whereas synchrony was not significantly related to flowering synchronization, nor to life form. (3) Nitrogen and carbohydrate content of fruit pulp did not vary in relation to phenology, whereas lipid content decreased from early to late ripening fruits. (4) No seasonal trends were found for variation in seed size or seed number per fruit. (5) Interactions with flowering phenology and developmental constraints are important in phenological fruiting patterns. Temporal variation in start of fruiting was partly (36%) explained by variation in flowering time. Seed weight variation explained 17% of variation in development time from flower to fruit. (6) Despite constraints from flowering and seed development, some adaptive adjustment in fruiting phenology is likely to be allowed for among the investigated species. Such an adaptive variation in fruiting phenology was suggested by intra-generic comparisons of Prunus and Vaccinium species.


Alcohol consumption increases non-adherence to ART among people living with HIV enrolled to the community-based care model in rural northern Uganda.
Non-adherence to anti-retroviral therapy (ART) is associated with considerable morbidity and mortality among people living with Human Immunodeficiency Virus (PLHIV). Community-based ART delivery model offers a decentralized and patient-centered approach to care for PLHIV, with the advantage of improved adherence to ART hence good treatment outcomes. However, data are limited on the magnitude of non-adherence to ART among PLHIV enrolled to the community-based ART model of care. In this study, we determined the frequency of non-adherence to ART and the associated factors among PLHIV enrolled to the community-based ART delivery model in a large health facility in rural northern Uganda. This analytic cross-sectional study randomly sampled participants from 21 community drug distribution points at the AIDS Support Organization (TASO) in Gulu district, northern Uganda. Data were collected using a standardized and pre-tested questionnaire, entered in Epi-Data and analyzed in Stata at univariate, bivariate, and multivariate analyses levels. Binary logistic regression analysis was used to determine factors independently associated with non-adherence to ART, reported using odds ratio (OR) and 95% confidence level (CI). The level of statistical significance was 5%. Of 381 participants, 25 (6.6%) were non-adherent to ART and this was significantly associated with alcohol consumption (Adjusted (aOR), 3.24; 95% CI, 1.24-8.34). Other factors namely being single/or never married (aOR, 1.97; 95% CI, 0.62-6.25), monthly income exceeding 27 dollars (aOR, 1.36; 95% CI, 0.52-3.55), being on ART for more than 5 years (aOR, 0.60; 95% CI, 0.23-1.59), receipt of health education on ART side effects (aOR, 0.36; 95% CI, 0.12-1.05), and disclosure of HIV status (aOR, 0.37; 95% CI, 0.04-3.20) were not associated with non-adherence in this setting. Non-adherence to ART was low among PLHIV enrolled to community-based ART delivery model but increases with alcohol consumption. Accordingly, psychosocial support programs should focus on alcohol consumption.


Observations on the joints of the hand.
Thirty-two hands (sixty-eighty years) were dissected to study configuration and spatial setting of the articular surfaces of the joints of the thumb in order to note the features which are associated with deviation, torsion and rotatory movements. Four varieties of the trapezial surface were encountered in the carpometacarpal joint: saddle-shaped, triangular, ovoid and semicylindrical. The last exhibited marked osteoarthrosis with formation of osteophytes.


Multi-slice CT angiography in the evaluation of patients with acute cerebrovascular disease--a promising new diagnostic tool.
Single-slice computed tomographic angiography (CTA) is an established imaging method for the cerebrovascular system (CVS), but it suffers from technical limitations with respect to the coherent high resolution visualization of longer vascular segments, such as the extra- and intracranial CVS. The recently introduced multi-slice (MS) technology has been attributed with a superior imaging quality for angiographic procedures due to increased scan speed and improved spatial resolution. The purpose of this study was to evaluate the suitability of multi-slice CTA (MS-CTA) for the assessment of the arteriovenous CVS in patients with acute symptoms of either arterial or venous occlusive diseases. 41 patients with clinically suspected acute cerebral ischaemia (hemispheric in 29 and vertebrobasilar in 12 patients) and 4 patients with suspected cerebral venous thrombosis (CVT) underwent CTA in a MS-CT scanner. In addition, doppler ultrasonography (DUS) was erformed in 34, magnetic resonance angiography (MRA) in 5 and digital subtraction angiography (DSA) in 6 patients. All findings were reviewed for stenoses or occlusion of the extra-and intracranial CVS and correlated with the clinical outcome. In 43 (96%) of 45 patients, MS-CTA yielded images of diagnostic quality with comprehensive visualization of the arterial and venous CVS including the cervical carotid bifurcation, the third segment of the major cerebral arteries and the dural sinus as well as internal cerebral veins. In 2 patients, assessment of the carotid bifurcation was limited because of tooth artefacts. In all patients, in whom imaging and clinical follow-up proved a non-lacunar infarction (n = 22), MS-CTA detected the underlying vascular pathology. Suspected CVT could be confirmed in 2 and ruled out in another 2 patients through MS-CTA. In conclusion, multi-slice CT an giography may be a promising new diagnostic tool for the rapid and comprehensive assessment of the arteriovenous CVS in patients with clinical signs of acute cerebrovascular diseases.


Bordetella pertussis epidemiology and evolution in the light of pertussis resurgence.
Whooping cough, or pertussis, is resurgent in many countries world-wide. This is linked to switching from the use of whole cell vaccines to acellular vaccines in developed countries. Current evidence suggests that this has resulted in the earlier waning of vaccine-induced immunity, an increase in asymptomatic infection with concomitant increases in transmission and increased selection pressure for Bordetellapertussis variants that are better able to evade vaccine-mediated immunity than older isolates. This review discusses recent findings in B. pertussis epidemiology and evolution in the light of pertussis resurgence, and highlights the important role for genomics-based studies in monitoring B. pertussis adaptation.


[The expression of MTS1 gene product in transitional mucosa adjacent to rectal carcinomas and its clinical significance].
To study the property of transitional mucosa (TM) adjacent to rectal carcinoma and the clinical significance of MTS1 gene deficit. We used the immunohistochemical methods to observe the range of TM adjacent to rectal carcinoma, and the immunohistochemical method to observe the expression of MTS1 gene product on TM, using normal mucosa and carcinoma tissue as control. The positive expression level of MTS1 gene product was the highest in the normal rectal mucosa, gradually defective in TM and carcinoma tissue (P < 0.05). The range of TM with MTS1 negative cases was prominently larger than that with MTS1 positive cases (P < 0.05). The inactivation of MTS1 gene is relative to the occurrence of rectal carcinoma, suggesting that the TM adjacent to rectal carcinoma possess as certain potential malignancy. TM is related to MTS1 gene expression deficit of rectal carcinoma, showing that MTS1 gene expression deficit or mutation may be a factor inducing transitional change adjacent to carcinoma.


Investigation of Relationship Between Small Noncoding RNA (sncRNA) Expression Levels and Serum Iron, Copper, and Zinc Levels in Clinical Diagnosed Multiple Sclerosis Patients.
In our study, we aimed to investigate the relationship between microRNA (miRNA) expression levels and serum iron (Fe), copper (Cu), and zinc (Zn) levels in Multiple sclerosis (MS) patients. Total RNA was isolated from peripheral venous blood containing ethylenediaminetetraacetic acid (EDTA) of MS patients and controls. Total RNA was labeled with Cy3-CTP fluorescent dye. Hybridization of samples was performed on microarray slides and arrays were scanned. Data argument and bioinformatics analysis were performed. Atomic absorption spectrophotometer method was used to measure serum Fe, Cu, and Zn levels. In our study, in bioinformatics analysis, although differently expressed miRNAs were not detected between 16 MS patients and 16 controls, hsa-miR-744-5p upregulation was detected between 4 MS patients and 4 controls. This may be stem from the patient group consisting of MS patients who have never had an attack for 1 year. Serum iron levels were detected significantly higher in the 16 MS patients compared to the 16 controls. This may be stem from the increase in iron accumulation based on inflammation in MS disease. According to the findings in our study, hsa-miR-744-5p upregulation has been determined as an early diagnostic biomarker for the development together of insulin resistance, diabetes mellitus associated with insulin signaling, and Alzheimer's diseases. Therefore, hsa-miR-744-5p is recommended as an important biomarker for the development together of diabetes mellitus, Alzheimer's disease, and MS disease. In addition, increased serum Fe levels may be suggested as an important biomarker for neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, and MS disease.


Relationship of hairless mouse skin surface temperature to wound severity and maturation time.
Skin surface temperature (SST) changes measured on live hairless mice are presented as a simple means of following wound healing. SST is generally determined by 3 factors which are the ambient temperature, the rate of water loss from the surface of the skin and the diffusion of thermal energy from the body's core. The SST increase immediately after a burn injury reflects the amount of thermal energy absorbed by the skin surface. For burns and other injuries, the drop in SST following injury, but after thermal equilibrium has been established, provides an early indication of the degree of impairment of the skin's barrier. Three kinds of mouse skin wounds, mechanical (tape stripping), thermal and chemical (phenol application), were investigated. SST nadirs ranged from 2.1 to 4.4 degrees C with mild to full-thickness burns, respectively. Except for the earliest moments after wounding, striking parallels were noted between SST and transepidermal water loss profiles for these injuries. The SST profile over the full course of wound healing clearly indicates the severity of the injury, the stages of wound maturation and the time to complete skin healing.


Ecological restoration of Xingu Basin headwaters: motivations, engagement, challenges and perspectives.
Over the past two decades, the headwaters of the Xingu Basin in the Amazon have been subjected to one of the highest deforestation rates in Brazil, with negative effects on both terrestrial and aquatic systems. The environmental consequences of forest land conversion have concerned the indigenous people living downstream, and this was the first motivation for the Y Ikatu Xingu campaign--'save the good water of the Xingu'. Among the objectives of the initiative was to restore riparian forests on private land across the basin. For a region where the rivers, rainstorms, forest remnants, distances and farms are huge, the challenges were equally large: crossing the biotic and abiotic thresholds of degradation, as well as addressing the lack of technology, know-how, seeds, forest nurseries, trained personnel and roads, and the lack of motivation for restoration. After 6 years, despite the remarkable advances in terms of technical innovation coupled with a broad and effective social involvement, the restored areas represent only a small portion of those aimed for. The still high costs of restoration, the uncertainties of legislation and also the global economy have been strong forces constraining the expansion of restored forests. Additional efforts and strategies are necessary to overcome these barriers.


Modified Lynch procedure for chronic frontal sinus diseases: rationale, technique, and long-term results.
The modified Lynch operation (Neel-Lake) differs in several ways from the operation described by Lynch. The operation begins with an intranasal anterior ethmoidectomy. The agger nasi cells are removed by curetting forward between the frontal process of the maxilla and the septum. The middle turbinate, normal-appearing mucosa of the frontal-ethmoid complex, and frontal process of the superior maxilla are preserved. Bone removal is limited in most cases to the anterior floor of the frontal sinus, a portion of the lacrimal bone, and the bone over the anterior ethmoid cells. Another important difference is the use of soft, nonreactive material (thin Silastic sheeting) to stent the nasal-frontal passageway. Removal of all the mucosa of the frontal-ethmoid-sphenoid complex is unnecessary for a good postoperative result, and the remaining normal mucosa hastens the process of reepithelialization of the nasal-frontal duct. The patients in our original study group have been observed for a period of 5 to 20 years (mean, 13.5 years) after the surgical procedure. This is the longest period of follow-up for any group of patients reported in the literature. The incidence of failures increased from 7% (one duct) to 20% (3 of 15 ducts) after an additional 7 years of follow-up.


Living Anatomy of the Pericardial Space: A Guide for Imaging and Interventions.
The pericardium of the human heart has received increased attention in recent times due to interest in the epicardial approach for cardiac interventions to treat cardiac arrhythmias refractory to conventional endocardial approaches. To support further clinical application of this technique, it is fundamental to appreciate the living anatomy of the pericardial space, as well as its relationships to the surrounding structures. The anatomy of the pericardial space, however, is extremely difficult regions to visualize. This is due to its complex 3-dimensionality, and the "potential" nature of the space, which becomes obvious only when there is collection of pericardial fluid. This potential space, which is bounded by the epicardium and pericardium, can now be visualized by special techniques as we now report, permitting appreciation of its living morphology. Current sources of knowledge are limited to the dissection images, surgical images, and/or illustrations, which are not necessarily precise or sufficient to provide relevant comprehensive anatomical knowledge to those undertaking the epicardial approach. The authors demonstrate, for the first time to their knowledge, the 3-dimensional living anatomy of the pericardial space relative to its surrounding structures. They also provide correlative anatomy of the left sternocostal triangle as a common site for subxiphoid access. The authors anticipate their report serving as a tool for education of imaging and interventional specialists.


Specific high performance liquid chromatographic determination of quinidine in serum, blood, and urine.
A reversed-phase high performance liquid chromatographic method for determination of quinidine in serum, blood, and urine has been developed. An alkylnitrile column is used with a mobile phase of acetonitrile in an acetate buffer. The method was rigorously tested and shown to be specific for quinidine using the following methods: comparison of capacity factors among methanolic reference standards of quinidine, known metabolites, and 36 other drugs; comparison of the quinidine capacity factor with the capacity factors from components in patient sera and urines, from which quinidine was selectively removed by thin-layer chromatography; and, correlation of quinidine concentrations in patient sera using ultraviolet absorbance versus fluorescence detection. Application of the method to a single-dose pharmacokinetic study, including serum protein binding and blood/serum concentration ratio measurements.


CD44v6 expression in gastroenteropancreatic neuroendocrine neoplasms: Clinicopathological correlation and prognosis.
Clinical course of gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) patients are determined by complicated and multifaceted factors. Ki-67 has been used to predict the behavior of NEN with statistically significant high probability. Immunohistochemical prognostic markers other than Ki-67 have been reported, but due to insufficient validation, they have not been used routinely. CD44 and its isoform variants showed significant inverse correlation with lymph node status, distant metastasis, and mortality in pancreatic neuroendocrine neoplasm (Pan-NEN). The aim of this study is to determine the prognostic value of CD44v6 expression among GEP-NENs. Immunohistochemical staining (IHC) of CD44v6 was studied in 26 formalin-fixed-paraffin-embedded (FFPE) specimens from GEP-NENs patients in the Srinagarind Hospital, Khon Kaen University, Thailand, between 2013 and 2018. Demographic data were collected. IHC staining result was interpreted based on H-score and correlated with neuroendocrine IHC markers, proliferation index, lymph nodes status, metastasis, and patients' survival. All cases showed variable staining for CD44v6 without statistically significant correlation with age, gender, histological grading, lymph node metastasis, distant metastasis, Ki-67 proliferative index, or neuroendocrine marker expression. Survival analysis showed association of higher CD44v6 expression with better prognosis (p = 0.033). Hazard ratio of CD44v6 low expression patients with age ≥ 49 was 12.736 (p = 0.028, 1.318-123.073), presence of lymph node metastasis was 8.267 (p = 0.036, 1.142-59.841), presence of distant metastasis 12.736 (p = 0.028, 1.318-123.073). Higher expression of CD44v6 IHC is significantly associated with better overall survival, histological grading, and Ki-67 index of GEP-NENs patients. CD44v6 IHC can be used as an additional prognostic immunohistochemical marker related to the metastatic status.


Thymosin beta 4 expression and nuclear transport are regulated by hMLH1.
For hMLH1, a key enzyme of DNA mismatch repair and frequently mutated in human cancers, several additional functions have been suggested. We now identified Thymosin beta4 (Tbeta4), an actin-binding and cell motility regulating protein, by bacterial two-hybrid screening. Interaction was confirmed by coimmunoprecipitation. Tbeta4 was weakly expressed in the hMLH1-deficient cell lines 293T and HCT-116. Reconstitution of hMLH1 resulted in strong expression of Tbeta4. Confocal laser microscopy revealed nuclear colocalization of both proteins. Reconstitution with hMLH1 mutants lacking a functional nuclear localization sequence resulted in cytoplasmatic retention of both proteins. After Tbeta4- or hMLH1-siRNA treatment, cell migration of hMLH1-proficient cells was markedly decreased. Our results show that hMLH1 interacts with Tbeta4 and regulates its expression and nuclear transport. Moreover, loss of hMLH1 causes Tbeta4 deprivation and results in reduced migratory activity in vitro. These data give insight into novel functions of hMLH1 and probably disease related dysregulated mechanisms.


HPV genotyping in biopsies of HSIL and invasive cervical cancers in women living with HIV: A cohort- and a nested -case control study.
To characterize HPV genotype distribution in HSIL and ICC- biopsies, of WLWH, in Europe, as compared to HIV-negative women. Cohort- and nested -case control study. We characterized HPV genotype distribution by performing PCR on HSIL and ICC biopsies from WLWH (n = 170); 85 cases were compared to 85 HIV-negative matched controls. The proportion of patients that might be protected by HPV vaccines was estimated. Among WLWH (median age 36 years-old, median duration of HIV infection 70,5 months, 79% under cART): the most frequently detected HPV were HPV16 (30%), HPV35 (16%), HPV58 (14,7%), HPV31 (13,5%), and HPV52 (11,7%). HPV16 was less frequently found in WLWH, originating from Central Africa (20,5%) compared to other African regions (35,5%) (p = 0,05) or world regions (38,8%) (p = 0,007). Multiple versus single high-risk HPV infections were associated with younger age (≤35 years)(odds ratio (OR) 2,65 (95%IC: 1,3-5,2,p = 0,002), lymphocyte CD4 count < 350 cells / µL (OR 2,7 (95%IC: 2-8,5; p = 0,005), use of cART for < 18 month OR 2,2 (95%IC: 1,1-4,5),p = 0,04) or a cumulative time with undetectable HIV viral load of less than 12 months (OR 4,2 (95%IC: 2-8.5,p = 0,001). HPV 31, 33 and 35 were more frequently detected in samples from WLWH than in HIV-negative controls (p < 0,05). The 9-valent vaccine would increase HPV protection, in HIV-positive and negative women (p < 0,001). WLWH are more frequently infected with high-risk HPV other than 16 and 18 than HIV-negative ones. The use of 9-valent vaccine may prevent HSIL or ICC in up to 85% of the women. Adding HPV 35 to the HPV vaccine panel, might improve vaccine effectiveness in WLWH.


New molecular techniques for microbial epidemiology and the diagnosis of infectious diseases.
A major aim of clinical microbiologists over the last century has been to demonstrate the presence of pathogenic microorganisms in clinical or pathologic samples associated with infectious diseases. With the development of molecular genetics over the last two decades, new technologies have become available that allow more sensitive and specific determinations to be made in shorter periods. Two considerable benefits have accrued: Epidemiologists are now capable of judging clonality among various clinical isolates more powerfully, permitting added accuracy in the evaluation of the epidemic spread of microbes, and clinicians have gained enormous ability to diagnose previously difficult-to-detect pathogens.


Trends and socioeconomic disparities in diabetes prevalence and quality of care among Israeli children; 2011-2018.
Despite Israel's universal health coverage, disparities in health services provision may still exist. We aimed to assess socioeconomic disparities in diabetes prevalence and quality of care among Israeli children, and to assess whether these changed over time. We used repeated cross-sectional analyses in the setting of the National Program for Quality Indicators in Community Healthcare. The data were derived from electronic medical records from Israel's four health maintenance organizations. The study population included all Israeli children aged 2-17 years in 2011-2018 (2018: N = 2,404,856). Socio-economic position (SEP) was measured using Central Bureau of Statistics data further updated by a private company (Points Business Mapping Ltd), and grouped into 4 categories, ranging from 1 (lowest) to 4 (highest). We used logistic regression to assess the association of SEP with diabetes prevalence, diabetes clinic visits, hemoglobin A1C (HbA1C) testing, and poor glycemic control (HbA1c > 9%), and assessed whether these changed over time. Diabetes prevalence increased with age and SEP, with a total of 3019 children with diabetes. SEP was positively associated with visiting a specialized diabetes clinic (age and sex adjusted Odds Ratio (aORSEP 4 vs. 1 2.45, 95% Confidence Interval (CI) 1.67-3.69)). Although children in higher SEPs were less likely to undergo HbA1c testing (aORSEP 4 vs. 1 0.54, 95% CI 0.40-0.72), they were also less likely to have poor glycemic control (aORSEP 4 vs. 1 0.25, 95% CI 0.18-0.34). Disparities were especially apparent among children aged 2-9 (6.5% poor glycemic control in SEP 4 vs. 38.2% in SEP 1). Poor glycemic control decreased over time, from 44.0% in 2011 to 34.1% in 2018. While poor glycemic control rates among children have improved, they remain high compared to rates in adults. Additionally, substantial socioeconomic gaps remain. It is eminent to study the causes of these disparities and develop policies to improve care provided to children in the lower SEP levels, to promote health equity.


Involvement of a nine-residue loop of streptokinase in the generation of macromolecular substrate specificity by the activator complex through interaction with substrate kringle domains.
The selective deletion of a discrete surface-exposed epitope (residues 254-262; 250-loop) in the beta domain of streptokinase (SK) significantly decreased the rates of substrate human plasminogen (HPG) activation by the mutant (SK(del254-262)). A kinetic analysis of SK(del254-262) revealed that its low HPG activator activity arose from a 5-6-fold increase in K(m) for HPG as substrate, with little alteration in k(cat) rates. This increase in the K(m) for the macromolecular substrate was proportional to a similar decrease in the binding affinity for substrate HPG as observed in a new resonant mirror-based assay for the real-time kinetic analysis of the docking of substrate HPG onto preformed binary complex. In contrast, studies on the interaction of the two proteins with microplasminogen showed no difference between the rates of activation of microplasminogen under conditions where HPG was activated differentially by nSK and SK(del254-262). The involvement of kringles was further indicated by a hypersusceptibility of the SK(del254-262).plasmin activator complex to epsilon-aminocaproic acid-mediated inhibition of substrate HPG activation in comparison with that of the nSK.plasmin activator complex. Further, ternary binding experiments on the resonant mirror showed that the binding affinity of kringles 1-5 of HPG to SK(del254-262).HPG was reduced by about 3-fold in comparison with that of nSK.HPG . Overall, these observations identify the 250 loop in the beta domain of SK as an important structural determinant of the inordinately stringent substrate specificity of the SK.HPG activator complex and demonstrate that it promotes the binding of substrate HPG to the activator via the kringle(s) during the HPG activation process.


Controversial use of vitellogenin as a biomarker of endocrine disruption in crustaceans: New adverse pieces of evidence in the copepod Eurytemora affinis.
In recent years, the interest in the use of vitellogenin (VTG) as a biomarker of endocrine disruption in fish has led to VTG being considered as a potential tool in invertebrates. Among aquatic invertebrate models in ecotoxicology, the copepods are considered as reference species in marine, estuarine and freshwater ecosystems. In this context, we identified a VTG cDNA in Eurytemora affinis. The Ea-VTG2 cDNA is 5416bp in length with an open reading frame (ORF) of 5310bp that encodes a putative protein of 1769 amino acids residues. Phylogenetic analysis confirmed the hypothesis of a VTG duplication event before the emergence of the copepod species. The analysis of the Ea-VTG2 expression by qPCR in males and females according to their reproductive stages allowed transcript basal levels to be determined. The expression pattern revealed a gradual increase of transcript levels during maturation in females. Important inter-sex differences were observed with a VTG level in males ranging from about 1900- to 6800-fold lower than in females depending on their stage. Moreover, the protein was only detected in ovigerous females. The inducibility of Ea-VTG2 by chemicals was studied in males exposed to either a model of endocrine disruptor in vertebrates i.e. 4-nonylphenol (4-NP) or a crustacean hormone i.e. Methyl Farnesoate (MF), and in males sampled from a multi-contaminated estuary. No induction was highlighted. The VTG should not be considered as an appropriate biomarker in E. affinis as previously suggested for other crustaceans.


Antenatal ultrasonic demonstration of fetal bowel.
Although ultrasound evaluation of the adult gastrointestinal tract is largely impossible because of bowel gas, the fetal bowel is fluid-filled and therefore not subject to this limitation. In our experience, the fetal bowel pattern can be recognized and antenatal abnormalities detected.


Community Stroke Rehabilitation: How Do Rural Residents Fare Compared With Their Urban Counterparts?
Rural living has been demonstrated to have an effect on a person's overall health status, and rural residing individuals often have decreased access to health and specialized rehabilitation services. The aim of this study was to determine if there are differences in recovery from stroke between urban and rural-dwelling stroke survivors accessing an in-home, community-based, interdisciplinary, stroke rehabilitation program. Data from a cohort of 1222 stroke survivors receiving care from the Community Stroke Rehabilitation Teams between January 2009 and June 2013 was analyzed. This program delivers stroke rehabilitation care directly in a person's home and community. Functional and psychosocial outcomes were evaluated at baseline, discharge, and six -month follow-up. A series of multiple linear regression analyses was performed to determine if rural versus urban status was a significant predictor of discharge and 6-month health outcomes. The mean age of the rural cohort was 68.8 (±13.1) years (53.6% male), and the urban cohort was 68.4 (±13.0) years (44.8% male). A total of 278 (35.4%) individuals were classified as living in a rural area using the Rurality Index for Ontario. In multivariate linear regression analysis, no significant differences on the Functional Independence Measure, the Stroke Impact Scale, the Hospital Anxiety and Depression Scale, or the Reintegration to Normal Living Index were found between urban and rural cohorts. When provided with access to a home-based, specialized stroke rehabilitation program, rural dwelling stroke survivors make and maintain functional gains comparable to their urban-living counterparts.


Cage-rotor induction motor inter-turn short circuit fault detection with and without saturation effect by MEC model.
The inter-turn short fault for the Cage-Rotor-Induction-Machine (CRIM) is studied in this paper and its local saturation is taken into account. However, in order to observe the exact behavior of machine, the Magnetic-Equivalent-Circuit (MEC) and nonlinear B-H curve are proposed to provide an insight into the machine model and saturation effect respectively. The electrical machines are generally operated near to their saturation zone due to some design necessities. Hence, when the machine is exposed to a fault such as short circuit or eccentricities, it is operated within its saturation zone and thus, time and space harmonics are integrated and as a result, current and torque harmonics are generated which the phenomenon cannot be explored when saturation is dismissed. Nonetheless, inter-turn short circuit may lead to local saturation and this occurrence is studied in this paper using MEC model. In order to achieve the mentioned objectives, two and also four-pole machines are modeled as two samples and the machines performances are analyzed in healthy and faulty cases with and without saturation effect. A novel strategy is proposed to precisely detect inter-turn short circuit fault according to the stator׳s lines current signatures and the accuracy of the proposed method is verified by experimental results.


Targeting MicroRNAs in Prevention and Treatment of Neurodegenerative Disorders.
Preclinical Research microRNAs (miRNAs) are small noncoding RNAs (ncRNAs) that are key regulators of gene expression. They act on wide range of targets by binding to mRNA via imperfect complementarity at 3' UTR. Evidence suggests that miRNAs regulate many biological processes including neuronal development, differentiation, and disease. Altered expression of several miRNAs has been reported in many neurodegenerative disorders (NDDs). Many miRNAs are altered in these diseases, but miRNA 15, miRNA 21, and miRNA 146a have been shown to play critical role in many neurodegenerative conditions. As these miRNAs regulate many genes, miRNA targeted approaches would allow concurrently targeting of multiple effectors of pathways that regulate disease progression. In this review, we describe the role of miRNAs in various NDDs and their potential as therapeutic tools in prevention and treatment of neurological conditions.


Clinical experience in diagnosis and management of superior semicircular canal dehiscence in children.
To identify clinical characteristics of pediatric superior semicircular canal dehiscence (SSCD) and explore suitable options of management. Retrospective review. The study comprised 10 patients with auditory and/or vestibular symptoms suspicious for SSCD. One patient pursued care at another institution, and two did not return for follow-up. Subsequently, seven patients (11 ears, 6 females and 1 male, aged 5-11 years) were included. Patients were evaluated using high-resolution temporal bone computed tomography. Those suspected of having SSCD underwent vestibular evoked myogenic potential testing for confirmation in addition to routine audiologic tests. All seven patients had auditory and/or vestibular impairment. Auditory symptoms included autophony, tinnitus, and conductive or mixed hearing loss. Bone conduction responses were occasionally better than 0 dB HL. Vestibular dysfunction included vertigo, often in response to loud noises, and chronic disequilibrium. One patient underwent surgical repair for disabling vestibular symptoms with dramatic improvement in both auditory and vestibular symptoms postoperatively. The remaining six were closely monitored with routine exams. In contrast to adults, children with SSCD usually present with auditory symptoms first, although they share some similarities with adults in clinical manifestations of SSCD. Our study shows that SSCD syndrome, a well-accepted clinical entity, exists in the pediatric population. Conservative management is preferred for children with SSCD; nevertheless, surgical intervention is necessary for those with disabling vestibular symptoms. To date, this is the first clinical case series of symptomatic pediatric patients with SSCD.


Myxofibrosarcoma of the hypopharynx.
Myxofibrosarcoma is common in the extremities, but rare in the head and neck region. Hypopharyngeal myxofibrosarcoma has not been reported previously. We report the first case of a patient with myxofibrosarcoma of the hypopharynx. We examined this patient once a month after the operation, and there has been no local recurrence and no distant metastasis. Sarcomas are rare in the hypopharynx, but we have to bear in mind their possibility. Though a low-grade myxofibrosarcoma is a low-grade malignancy, complete resection should be done. We have to pay more attention planning the treatment for neoplastic diseases.


The importance of carrying capacity, fertility, and viability for the competitive ability of populations.
A simple mathematical model is analyzed which describes the behaviour of a population under the influence of viability and fertility as well as carrying capacity and competition by another species. One locus with two alleles determining viability, fertility, and carrying capacity is considered. Throughout the analysis absolute rather than relative numbers are used. The following results have been obtained: 1. The species producing more zygotes wins the competition. 2. Absolute numbers must be used for viability and fertility in theoretical considerations, because the outcome of competition may be changed by using different absolute numbers of the same relation. 3. Differences in viability are amplified by limiting the number of individuals. 4. Differences in every parameter can be compensated by any other parameter.


Studies on schistosomiasis in the Niger Delta: Schistosoma intercalatum in the urban city of Port Harcourt, Nigeria.
Ova of S. intercalatum have been found in the urban city of Port Harcourt in the Niger Delta area of Nigeria, following examination of stool and urine samples from 1,709 persons (5-15 years of age) resident in various parts of the city. The ova occurred only in urine, with prevalence ranging from 1.0% to 9.8% with an overall prevalence of 5.7%. The intensity of the infection was low. Most infected individuals had counts of less than 500 ova in total bladder content. There was no significant difference in either the prevalence or intensity of the infection among the sexes (Male; prevalence 6.1%, intensity 527.3 vs Female; prevalence 5.4%, intensity 500.9). No case of infection with either S. haematobium or S. mansoni was encountered in the study. Malacological surveys in the gutters, creeks, streams and stagnant waterbodies within the city showed the presence of Lymnaea natalensis, Bulinus forskalii, Pila ovata, Melanoides tuberculata, Physa sp., Lanistes ovum and Segmentorbis sp. B. forskalii is indicated as the probable vector of S. intercalatum in the city. The growing problem of urban schistosomiasis in tropical Africa is discussed. Further studies on urban transmission and epidemiology of schistosomiasis in the Niger Delta area of Nigeria is also indicated.


A comprehensive evaluation of the association of radiographic measures of lateralization on clinical outcomes following reverse total shoulder arthroplasty.
Although reverse total shoulder arthroplasty (RTSA) has excellent reported outcomes and satisfaction, patients often have postoperative limitations in range of motion (ROM), specifically internal rotation. Increased lateralization is thought to improve ROM following RTSA. The purpose of this study was to evaluate the association between radiographic measurements of lateralization and postoperative ROM and clinical outcome scores following RTSA. The authors hypothesized that increased radiographic lateralization would be associated with improved postoperative ROM, specifically internal rotation, but have no significant association with clinical outcome scores. Patients who underwent RTSA with a 135° neck-shaft angle prosthesis and minimum 2-year clinical and radiographic follow-up were included and retrospectively reviewed. Postoperative radiographs were evaluated for several lateralization measurements including the lateralization shoulder angle (LSA), distance from the lateral border of the acromion to the lateral portion of the glenosphere, distance from the glenoid to the most lateral aspect of the greater tuberosity, and the distance from the lateral aspect of the acromion to the most lateral aspect of the greater tuberosity. Linear regression analyses were used to evaluate the independent association of each radiographic measurement of lateralization on forward flexion, external rotation, internal rotation, and the American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) index score at 2 years postoperation. Receiver operating characteristic (ROC) curves were constructed to identify significant thresholds of each radiographic lateralization measurement. A total of 203 patients were included. For internal rotation, a greater LSA (P = .007), shorter acromion to glenosphere distance (meaning more glenoid lateralization) (P = .005), and a greater acromion to greater tuberosity distance (with the tuberosity more lateral to the acromion) (P = .021) were associated with improved internal rotation. Overall, ROC analysis demonstrated very little significant data, the most notable of which was the LSA, which had a significant cutoff of 82° (sensitivity 57%, specificity 68%, P = .012). Of the numerous radiographic measures of lateralization after RTSA, the LSA is the most significantly associated with outcomes, including improved internal rotation and a decrease in forward flexion and ASES score. The clinical significance of these statistically significant findings requires further study, as the observed associations were for very small changes that may not represent clinical significance.


Whole-exome sequencing study of hypospadias.
Hypospadias results from the impaired urethral development, which is influenced by androgens, but its genetic etiology is still unknown. Through whole exome sequencing analysis, we identified NR5A1, SRD5A2, and AR as mutational hotspots in the etiology of severe hypospadias, as these genes are related to androgen signaling. Additionally, rare damaging variants in cilia-related outer dynein arm heavy chain (ODNAH) genes (DNAH5, DNAH8, DNAH9, DNAH11, and DNAH17) (p = 8.5 × 10-47) were significantly enriched in hypospadias cases. The Dnah8 KO mice exhibited significantly decreased testosterone levels, which had an impact on urethral development and disrupted steroid biosynthesis. Combined with trios data, transcriptomic, and phenotypical and proteomic characterization of a mouse model, our work links ciliary genes with hypospadias. Overall, a panel of ODNAH genes with rare damaging variants was identified in 24% of hypospadias patients, providing significant insights into the underlying pathogenesis of hypospadias as well as genetic counseling.


Isolation and mapping of a novel human kidney- and liver-specific gene homologous to the bacterial acetyltransferases.
Using the differential display method to detect tissue-specific genes, we isolated a novel human gene, designated TSC501, that is expressed in kidney and liver. The cDNA contained an open reading frame of 681 nucleotides encoding 227 amino acids. The predicted product showed homologies in amino acid sequence to three different bacterial acetyltransferases, enzymes that are involved in drug resistance. Radiation hybrid mapping localized this gene to human chromosome bands 2p12-p13.1.


Historical Y. pestis Genomes Reveal the European Black Death as the Source of Ancient and Modern Plague Pandemics.
Ancient DNA analysis has revealed an involvement of the bacterial pathogen Yersinia pestis in several historical pandemics, including the second plague pandemic (Europe, mid-14(th) century Black Death until the mid-18(th) century AD). Here we present reconstructed Y. pestis genomes from plague victims of the Black Death and two subsequent historical outbreaks spanning Europe and its vicinity, namely Barcelona, Spain (1300-1420 cal AD), Bolgar City, Russia (1362-1400 AD), and Ellwangen, Germany (1485-1627 cal AD). Our results provide support for (1) a single entry of Y. pestis in Europe during the Black Death, (2) a wave of plague that traveled toward Asia to later become the source population for contemporary worldwide epidemics, and (3) the presence of an historical European plague focus involved in post-Black Death outbreaks that is now likely extinct.


Determination of free and total sulfur dioxide in wine samples by vapour-generation inductively coupled plasma-optical-emission spectrometry.
Sulfur dioxide (SO(2)) is used as a preservative and stabilizer in wine production to prevent undesired biochemical processes in the must and the final product. The concentration of SO(2) is restricted by national regulations. There are two main forms of SO(2) in wine-free (inorganic forms) and bound (fixed to organic compounds, e.g. aldehydes). Iodometric titration is commonly employed for determination of SO(2) concentration (either by direct titration or after pre-separation by distillation); other techniques are also used. In this work inductively coupled plasma-optical-emission spectrometry with vapour generation was used for determination of free and total SO(2) in wine. Gaseous SO(2) is released from the sample by addition of acid and swept into the ICP by an argon stream. The intensity of the sulfur atomic emission lines is measured in the vacuum UV region. Determination of total SO(2) is performed after hydrolysis of bound forms with sodium hydroxide (NaOH). Concentrations of acid for vapour generation and NaOH for hydrolysis were optimised. The method was used for determination of free and total SO(2) in red and white wine samples and results were compared with those from iodometric titration.


Law and order: assessing and enforcing compliance with ontological modeling principles in the Foundational Model of Anatomy.
The objective of this study is to provide an operational definition of principles with which well-formed ontologies should comply. We define 15 such principles, related to classification (e.g., no hierarchical cycles are allowed; concepts have a reasonable number of children), incompatible relationships (e.g., two concepts cannot stand both in a taxonomic and partitive relation), dependence among concepts, and the co-dependence of equivalent sets of relations. Implicit relations--embedded in concept names or inferred from a combination of explicit relations--are used in this process in addition to the relations explicitly represented. As a case study, we investigate the degree to which the Foundational Model of Anatomy (FMA)--a large ontology of anatomy--complies with these 15 principles. The FMA succeeds in complying with all the principles: totally with one and mostly with the others. Reasons for non-compliance are analyzed and suggestions are made for implementing effective enforcement mechanisms in ontology development environments. The limitations of this study are also discussed.


A simple flash sintering setup under applied mechanical stress and controlled atmosphere.
Most flash sintering experimental set-ups use dog bone-shaped specimen and DC current, which results in heterogeneously distributed densification and grain growth throughout the sample. This is the reason why only the sample's core characteristics after flash are taken into account. On the other hand, some recent procedures suggest the use of cylindrical pellets, which have some advantages compared to the traditional mode as the use of easily conformed samples and its final uniformity. Our new experimental set-up offers the possibility of atmosphere control and pressure application. Also the electrodes material change can be easily made when necessary. Shrinkage measurements and impedance spectroscopy are realized in situ and experimental parameters, as oven heating for example, can be varied to control microstructure changes. •Sample can be entirely recovered at the end of the experiment and can be analyzed throughout its entire extension, including regions in contact with the electrodes that may present some differences from pellets inner part.•The use of AC current enables the study of different frequencies effects.•Experimental set-up can be adapted to different kinds of electrolytes (samples), easily changing electrode's material and atmosphere.


T-type Ca²⁺ channels in cerebral arteries: approaches, hypotheses, and speculation.
Cerebral blood flow is controlled by a network of resistance arteries that dilate and constrict to mechanical and chemical stimuli. Vasoactive stimuli influence arterial diameter through alterations in resting membrane potential and the influx of Ca²⁺ through voltage-gated Ca²⁺ channels. Historically, L-type Ca²⁺ channels were thought to be solely expressed in cerebral arterial smooth muscle. Recent studies have, however, challenged this perspective, by providing evidence of T-type Ca²⁺ channels in vascular tissues. This perspective piece will introduce T-type Ca²⁺ channels, their electrophysiological properties, and potential roles in arterial tone development. We begin with a brief overview of Ca²⁺ channels and a discussion of the approaches used to isolate this elusive conductance. We will then speculate on how the two T-type Ca²⁺ channels expressed in cerebral arterial smooth muscle might differentially influence arterial tone. This discovery of T-type Ca²⁺ channels alters our traditional understanding of Ca²⁺ dynamics in vascular tissue and fosters new avenues of research and insight into the basis of arterial tone development.


A perspective on diet, epigenetics and complex diseases: where is the field headed next?
Dietary factors can regulate epigenetic processes during life, modulating the intracellular pools of metabolites necessary for epigenetic reactions and regulating the activity of epigenetic enzymes. Their effects are strong during the prenatal life, when epigenetic patterns are written, allowing organogenesis. However, interactions between diet and the epigenome continue throughout life and likely contribute to the onset and progression of various complex diseases. Here, we review the contribution of dietary factors to the epigenetic changes observed in complex diseases and suggest future steps to better address this issue, focusing on neurobehavioral, neuropsychiatric and neurodegenerative disorders, cardiovascular diseases, obesity and Type 2 diabetes, cancer and inflammatory skin diseases.


Thermoinactivation mechanism of glucose isomerase.
In this article, the mechanisms of thermoinactivation of glucose isomerase (GI) from Streptomyces rubiginosus (in soluble and immobilized forms) were investigated, particularly the contributions of thiol oxidation of the enzyme's cysteine residue and a "Maillard-like" reaction between the enzyme and sugars in high fructose corn syrup (HFCS). Soluble GI (SGI) was successfully immobilized on silica gel (13.5 microm particle size), with an activity yield between 20 and 40%. The immobilized GI (IGI) has high enzyme retention on the support during the glucose isomerization process. In batch reactors, SGI (half-life =145 h) was more stable than IGI (half-life =27 h) at 60 degrees C in HFCS, whereas at 80 degrees C, IGI (half-life =12 h) was more stable than SGI (half-life =5.2 h). IGI was subject to thiol oxidation at 60 degrees C, which contributed to the enzyme's deactivation. IGI was subject to thiol oxidation at 80 degrees C, but this did not contribute to the deactivation of the enzyme. SGI did not undergo thiol oxidation at 60 degrees C, but at 80 degrees C SGI underwent severe precipitation and thiol oxidation, which caused the enzyme to deactivate. Experimental results show that immobilization suppresses the destabilizing effect of thiol oxidation on GI. A "Maillard-like" reaction between SGI and the sugars also caused SGI thermoinactivation at 60, 70, and 80 degrees C, but had minimal effect on IGI. At 60 and 80 degrees C, IGI had higher thermostability in continuous reactors than in batch reactors, possibly because of reduced contact with deleterious compounds in HFCS.


Inversion of 'flourescent' segment in chromosome 3: a polymorphic trait.
The frequency of the 'inversion' of flourescent constitutive heterochromatin in chromosome 3 was the same in a sample of 370 retarded persons as in a sample of 222 mentally normal men. It can be concluded that this 'inversion' is not associated with mental retardation. This variant is more common (4%) in the Canadian population we studied than in samples reported by most other authors (0-1.7%). Possibly the founder effect could play a role in the differences. Two cases of homozygotes for this 'inversion' were identified.


Developmental patterns and individual differences in responding to social feedback: A longitudinal fMRI study from childhood to adolescence.
Learning to control behavior when receiving feedback underlies social adaptation in childhood and adolescence, and is potentially strengthened by environmental support factors, such as parents. This study examined the neural development of responding to social feedback from childhood to adolescence, and effects of parental sensitivity on this development. We studied these questions in a 3-wave longitudinal fMRI sample (ages 7-13 years, n = 512). We measured responses to feedback using the fMRI Social Network Aggression Task through noise blasts following peer feedback and associated neural activity, and parental sensitivity using observations of parent-child interactions during Etch-a-Sketch. Results revealed largest reductions in noise blasts following positive feedback between middle and late childhood and following negative feedback between late childhood and early adolescence. Additionally, brain-behavior associations between dorsolateral prefrontal cortex activation and noise blast durations became more differentiated across development. Parental sensitivity was only associated with noise blast duration following positive feedback in childhood, but not in adolescence. There was no relation between parental sensitivity and neural activity. Our findings contribute to our understanding of neural development and individual differences in responding to social feedback, and the role of parenting in supporting children's adaption to social feedback.


Lack of the cysteine protease inhibitor cystatin C promotes atherosclerosis in apolipoprotein E-deficient mice.
Degradation of extracellular matrix plays an important role in growth and destabilization of atherosclerotic plaques. Cystatin C, inhibitor of the collagen- and elastin-degrading cysteine proteases of the cathepsin family, is produced by virtually all cell types. It is present in the normal artery wall but severely reduced in human atherosclerotic lesions. To determine the functional role of cystatin C in atherosclerosis, we crossed cystatin C-deficient (cysC(-/-)) mice with apolipoprotein E-deficient (apoE(-/-)) mice. After 25 weeks of atherogenic diet, mice lacking apoE and cystatin C (cysC(-/-) apoE(-/-)) had larger subvalvular plaques compared with cysC(+/+) apoE(-/-) mice (766,000+/-20,000 microm2 per section versus 662,000+/-19,000 microm2 per section; P=0.001), suggesting an atheroprotective role of cystatin C. The plaques from cysC(-/-) apoE(-/-) mice were characterized by increased total macrophage content. To determine which cellular source is important for the antiatherosclerotic effect of cystatin C, we performed bone marrow transplantations. ApoE(-/-) mice were transplanted with either cysC(-/-) apoE(-/-) or cysC(+/+) apoE(-/-) bone marrow. No significant differences in plaque area, macrophage, collagen, or lipid content of subvalvular lesions between the 2 groups were detected. The result suggests that the protective role of cystatin C in atherosclerosis is dependent primarily on its expression in nonhematopoietic cell types.


KRAS mutational test for metastatic colorectal cancer patients: not just a technical problem.
The identification of KRAS and BRAF mutations as predictive molecular alterations of resistance to EGF receptor monoclonal antibody therapy in metastatic colorectal cancer have significantly improved the selection of patients more likely to be eligible for the treatment with these targeted agents. Several methods are available for KRAS and BRAF mutation detection but few studies have compared different techniques, especially in the clinical setting. In this article, we contextualize the wobble-enhanced amplification refractory mutation sequencing method for the identification of KRAS and BRAF mutations with the other methodologies frequently used for the assessment of these alterations in colorectal cancer, discussing advantages and limitations over other frequently used diagnostic methods.


Screening for placental insufficiency in high-risk pregnancies: is earlier better?
To compare a profile of placental function between the first and second trimesters in pregnancies at high risk of adverse perinatal outcomes attributable to placental insufficiency. Prospective cohort study in 61 singleton pregnancies. Uterine artery Doppler and placental morphology (shape and texture) were determined at 11-13(+6) weeks and at 18-23(+6) weeks. First trimester (pregnancy-associated placental protein-A [PAPP-A]) and second trimester (total hCG and alpha fetoprotein [AFP]) serum biochemistry were determined. The two screening periods were compared for the prediction of a range of severe adverse perinatal outcomes (intrauterine growth restriction [IUGR], abruption, severe pre-eclampsia/HELLP syndrome, delivery<32 weeks, or stillbirth). Adverse perinatal outcomes occurred in 14 (23%) women; 3 (4.9%) losses<20 weeks, 2 (3.3%) stillbirths>20 weeks, 4 (6.6%) IUGR, 7 (11.5%) severe pre-eclampsia/HELLP syndrome, and 10 (16.4%) deliveries<32 weeks. Abnormal second trimester placental morphology was significantly associated with adverse outcome [+LR: 3.6, 95% CI: 1.3-8.5; -LR: 0.63, 95% CI: 0.36-0.93; p=0.025], as was > or = 1 abnormal second trimester tests [+LR: 5.9, 95% CI: 1.6-24; -LR: 0.68, 95% CI: 0.59-0.89; p=0.005] or > or = 2 abnormal second trimester tests [+LR: 3.6, 95% CI: 1.3-7.7; -LR: 0.58, 95% CI: 0.27-0.94; p=0.035]. No combination of first trimester tests significantly predicted severe adverse perinatal outcomes. A study sample size of 822 women with similar high-risk characteristics would be needed in order to refute the conclusion that present methods of first trimester screening are not inferior to second trimester screening for severe placental insufficiency (p=0.05, power 80%, z-test). In clinically high-risk pregnancies, prediction of adverse perinatal outcomes using placental function testing is more effective in the second compared with the first trimester.


Saccharomyces cerevisiae show low levels of traversal across the human blood brain barrier in vitro.
Saccharomyces cerevisiae is generally considered safe, and is involved in the production of many types of foods and dietary supplements. However, some isolates, which are genetically related to strains used in brewing and baking, have shown virulent traits, being able to produce infections in humans, mainly in immunodeficient patients. This can lead to systemic infections in humans. In this work, we studied S. cerevisiae isolates in an in vitro human blood brain barrier model, comparing their behaviour with that of several strains of the related pathogens Candida glabrata and Candida albicans. The results showed that this food related yeast is able to cross the blood brain barrier in vitro. However, in contrast to C. glabrata and C. albicans, S. cerevisiae showed very low levels of traversal. We conclude that using an in vitro human blood brain barrier model with S. cerevisiae can be useful to evaluate the safety of S. cerevisiae strains isolated from foods.


Saccadic intrusions in Alzheimer-type dementia.
Horizontal eye-movement responses of four patients with Alzheimer-type dementia were recorded using the infrared oculographic technique. Abnormally frequent saccadic intrusions occurred during the fixation and slow, smooth pursuit tasks in all four patients. Saccadic intrusions have previously been reported in the literature to occur in normals, in strabismus, in patients with certain neurological disorders, and in schizophrenic patients. This is the first report of a group of Alzheimer-type dements with an eye movement abnormality which cannot be regarded as an ocularmotor reflection of diffuse cerebral dysfunction.


[Diagnosis and Treatment Outcomes and Influencing Factors of Multidrug-Resistant Tuberculosis Based on Patient Pathway].
Multidrug-resistant tuberculosis (MDR-TB) has become one of the major challenges in the global tuberculosis (TB) control.Despite years of efforts on MDR-TB control,the treatment success rates in China have increased slowly,which indicates possible deficiencies in the management of prevention and control work.Therefore,it is necessary to analyze the current status of MDR-TB prevention and treatment based on the patient pathway.This review summarizes the current drop-out situation of MDR-TB patients in the diagnosis and treatment pathway and the factors affecting patients' outcomes in the whole pathway,so as to provide a scientific reference for the prevention and control of MDR-TB.


Clinical Treatment Options Infectious Diseases: Update on PrEP Implementation, Adherence, and Advances in Delivery.
Pre-exposure prophylaxis (PrEP) is an effective and evidence-based HIV-prevention option and is recommended for individuals with substantial risk for HIV infection [1]. Randomized controlled trials have demonstrated that daily oral PrEP dramatically reduces the risk of HIV infection when it is taken as directed. Concerns regarding widespread emergence of antiretroviral resistance attributable to PrEP and behavioral disinhibition have to date not been observed in clinical trials and open-label demonstration projects. PrEP has great potential as part of an HIV risk reduction strategy and barriers to wider implementation including community education, prescriber availability, and elimination of financial barriers should be aggressively pursued. Adherence is critical to PrEP efficacy and has varied across study populations; developing and refining ways of measuring and supporting adherence is essential to the success of PrEP. Evaluation of long-acting medications and alternative formulations for PrEP is underway and may lead to the wider implementation and impact of PrEP.


A developmental study on types and frequency distribution of short apneas (3 to 15 seconds) in term and preterm infants.
We measured the frequency distribution and the ventilatory correlates of the various types of apneas 3 to 15 s long during sleep in eight term infants (birth weight 3.65 +/- 0.16 kg; gestational age 39.5 +/- 0.3 wk) and eight preterm infants (birth weight 2.07 +/- 0.18 kg; gestational age 34.3 +/- 0.4 wk). Each infant was studied on five to seven occasions from birth to 56 wk of postconceptual age using a modified flow-through system. Sixty-six paired epochs of quiet sleep (1163 min) and rapid eye movement sleep (829 min) were analyzed in term infants and 85 paired epochs of quiet sleep (1553 min) and rapid eye movement sleep (1328 min) in preterm infants. Of the 783 apneas recorded in term infants 82% were central, 1.5% obstructive, 0.5% mixed, and 16% were of the breath-holding type; the corresponding figures for the 4086 apneas recorded in preterm infants were 93, 0.5, 1.0, and 5.5%. This distribution was similar in the two sleep states but term infants had a higher percentage of breath-holding apneas than preterm infants (p less than 0.01). In preterm infants the rate of central apneas decreased with postnatal age (p less than 0.01); in term infants the rate did not change significantly. The duration of apneas showed a modal distribution for central apneas at about 8 s for both groups during the 1st month of life (p less than 0.05). The findings suggest: 1) apneas in the newborn and early infancy are primarily central and are more frequent in preterm than in term infants.(ABSTRACT TRUNCATED AT 250 WORDS)


All is not lost: learning from 9p21 loss in cancer.
The cancer research community continues to search for additional biomarkers of response and resistance to immune checkpoint treatment (ICT). The ultimate goal is to direct the use of ICT in patients whose tumors are most likely to benefit to achieve a refinement that is equivalent to that of a genotype-matched targeted treatment. Dissecting the mechanisms of ICT resistance can help us characterize ICT nonresponders more efficiently. In this opinion, we argue that there may be additional knowledge gained about immune evasion in cancer by analyzing the loss of the human 9p21.3 locus; as an example, we highlight findings of 9p21.3 loss from the investigator-initiated, pan-cancer INSPIRE study, in which patients were treated with pembrolizumab (anti-PD-1 antibody) ICT.


Lipopolysaccharide-induced chorioamnionitis and postnatal lung injury: The beneficial effects of L-citrulline in newborn rats.
The lung architecture of newborns appears to be affected by an inflammatory reaction to maternal choriodecidual layer infection. L-citrulline (L-Cit) was administered to pregnant rats exposed to intra-amniotic lipopolysaccharide (LPS)-induced chorioamnionitis to investigate its effect on neonatal lung injury. The pups were assigned to four experimental groups: 1- pups exposed to intra-amniotic NaCl but not to postnatal L-Cit (Controls); 2 - pups exposed to intra-amniotic NaCl as well as to postnatal L-Cit treatment (L-Cit group); 3 - pups exposed to prenatal LPS but not to postnatal (LPS); 4- pups exposed to prenatal LPS as well as to postnatal L-Cit treatment (LPS + L-Cit). Some pups in each group were sacrificed on postnatal (P) day 3 and others on day 7. The pups' lungs were harvested for morphometric analysis; cytokine, arginase 1, and VEGF values were quantified. Serum arginine, citrulline, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine, NG-monomethyl arginine, and homoarginine levels were determined using UPLC-MS/MS. L-Cit attenuated the disruption of alveolar growth in the LPS + L-Cit group. Arginine, homo-arginine, and ADMA levels fell in the LPS treated groups. Arginine and ADMA rose at P7 in the L-Cit group whose members also showed higher VEGF levels with respect to the Controls. The Controls, instead, showed higher IL-10 and IL-1β values with respect to the L-Cit group at P7. Arginase 1 was higher in the LPS groups with respect to the Controls at P7. L-Cit improved alveolar and vascular growth diminishing the lung inflammatory response in the newborn rats exposed to intra-amniotic LPS. The ADMA/DDAH/NO pathway appeared to counteract proinflammatory cytokine production and to sustain macrophage migration.


End-user preferences to enhance prospects for varietal acceptance and adoption in potato breeding in Uganda.
Potato varieties have diverse biophysical characteristics, so it is important for breeders to have the capacity to choose those that meet the preferences of end users, such as mealiness, firmness, and taste, among others. Combining user preferences with descriptive information regarding the sensory characteristics of boiled potatoes can contribute to the improvement of consumer-driven varieties. This study aimed to factor in the preferences of end users to improve the prospects for varietal acceptance, adoption, and discrimination among genotypes in potato breeding. The priority quality traits (traits that play the most significant roles in acceptance and adoption) of the boiled potatoes were determined by evaluating gender and livelihood using the G+ tool. The G+ tool is designed to assess gender impact on roots, tubers and bananas (RTB) traits by serving as a validation check to reflect on important gender-based issues in agricultural food systems in order to reduce harm and promote positive impact. Potato genotypes were differentiated by penetration (textural parameters as measured by standard texture probe) and the procedure was repeatable, as there was no significant difference between the cooking replicates at 40 min of cooking. Instrument-based texture parameters, such as penetration peak force (hardness/firmness) and area (area under the curve, which represents energy needed to penetrate) of boiled potato tubers were significantly associated with sensory attributes such as fracturability and hardness in the mouth. An attempt to differentiate genotypes using near-infrared spectroscopy (NIRS) revealed that the average results observed for the calibration for yellow color (r2 = 0.70), homogeneity of color (r2 = 0.48), moisture in mass (r2 = 0.40), and uniformity of texture (r2 = 0.56) suggested that these parameters could be used for initial breeding screening purposes. The preferred traits of the boiled potato can be integrated into the potato-breeding program/product profile. Near-infrared spectroscopy shows strong potential to predict potato color and the ability of NIRS models to predict some texture attributes is also promising. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Quantitative analysis of survival of hypoglossal neurons in neonatally nerve-injured rats: Correlation with milk intake.
Tongue movement innervated by the hypoglossal (XII) nerve is essential for the survival of neonatal rats. The pups with bilateral XII nerve resection failed to suckle milk and did not survive, and the pups with unilateral XII nerve resection showed disturbed suckling capability and lower survival rates. The present study was performed to investigate the relation between neuronal population and milk intake of developing rats that had received various degrees of crush injuries to the unilateral XII nerve during the neonatal period. The right XII nerve of postnatal day 1 (P1) pups was crushed and milk intake was estimated at 3 days and 6 days after the nerve injury. As nerve injury at the neonatal stage results in death of axotomized neurons, varying degrees of crushing was estimated by the number of survived motor neurons. In nerve-crushed rats, the populations of XII motor neurons and amounts of milk intake were reduced in a varied manner. Statistically significant positive correlations were observed between increasing XII neuron survival and increasing milk intake at 3 (r=0.62) and 6 (r=0.71) days after the nerve injury. The results indicate that there is a strong relationship between the number of XII motor neurons and the amount of milk intake in neonatally XII nerve-injured rats.


Three novel Cas12a orthologs with robust DNA cleavage activity suitable for nucleic acid detection.
Developing rapid and accurate pathogen detection methods is increasingly important, and CRISPR-Cas system can be optimized for this purpose. CRISPR-Cas12a is a single RNA-guided endonuclease system with the potential for nucleic acid detection. There is a broad diversity among Cas12a nucleases with robust detection capability. Herein, we characterised three Cas12a orthologs (ObCas12a, MbCas12a, and ScCas12a), including cis- and trans-cleavage activities, the identification of PAM, single-base resolution ability, and the application for nucleic acid detection. These Cas12a orthologs displayed robust cis- and trans-cleavage activities, and performed well in terms of specificity and sensitivity for nucleic acid detection. Furthermore, they have subtle differences in single-base resolution and recognised PAM sites in vitro. Therefore, these Cas12a nucleases are candidate proteins for CRISPR-based diagnostic methods. Addition of these enzymes to the nucleic acid detection toolbox will further expand the utility of this powerful technology.


False-positive "halo" sign on testicular scintigraphy in a 5-year-old boy with epididymitis and hydrocele.
Scintigraphic differentiation between acute torsion, hydrocele and testicular or scrotal abscess can be difficult. Doppler sonography may provide useful complimentary information toward diagnosis. The authors describe a 5-year-old child where epididymitis with hydrocele was misdiagnosed as testicular torsion on scrotal scintigraphy.


Determination of ethylenediaminetetraacetic acid base on the reversion of fluorescence quenching of 2-pyridinecarbaldehyde-p-phenyldihydrazone by ferric iron.
A fast and sensitive fluorometric method for determination of an emerging pollutant, ethylenediaminetetraacetic acid (EDTA), was proposed based on the reversion of fluorescence quenching of 2-pyridinecarbaldehyde-p-phenyldihydrazone by ferric iron. It was found that Fe(3+) could selectively quench the fluorescence of 2PC-PPH, while EDTA could recover it due to its strong coordination ability with Fe(3+). Based on this, we established an "Off and On" fluorescence method for determination of EDTA. Under the optimum conditions, the linear range and detection limit (3S/N) for EDTA determination were 2.0 × 10(-6)~1.4 × 10(-5) mol L(-1) and 1.5 × 10(-7) mol L(-1), respectively. The relative standard deviation for the determination of 7.0 × 10(-6)mol L(-1) EDTA was 3.7% (n=11). The method was successfully applied to determination of EDTA in tap water, lake water and investigating degradation of EDTA by TiO2/UV process.