Prevalence of antibodies to hepatitis C virus in apparently healthy Port Harcourt blood donors and association with blood groups and other risk indicators.
Testing for hepatitis C virus (HCV) is not yet mandatory in blood transfusion laboratories in Port Harcourt, Nigeria, so the current prevalence rate of this infection in our locality is unknown. The aim of this study was to determine the prevalence of HCV among apparently healthy blood donors in our area and also to assess some of the risk factors associated with the infection. The presence of anti-HCV antibodies was determined in the serum of 300 blood donors in Port Harcourt, Nigeria. A second-generation rapid screening test, the HEP C SPOT HCV assay was used. Initial reactive results were confirmed by repeat testing with UBI HCV EIA 4.0 enzyme immunoassay. The ABO and Rh blood groups of donors were also determined using standard serological procedures. The majority of our blood donor population was constituted of males (88%) and commercial donors (63%). The blood group distribution of the donors was as follows: O RhD-positive (73%), AB RhD-positive. (4.0%), A RhD-positive (10.0%), B RhD-positive (3.0%), O RhD-negative (4.0%), A RhD-negative (3.0%), AB RhD-negative (1.0%) and B RhD-negative (2.0%). Fifteen of the 300 donors were positive for HCV, giving a prevalence rate of 5.0% in this study population. The age group 21-30 years was identified as the highest risk group with 60% of the subjects with HCV infection being in this group, compared to 20% each in the age groups 31-40 years and 41-50 years old. Twelve of the 15 (80%) HCV-positive subjects were commercial donors. The prevalence of HCV was statistically significantly higher among female donors than among male donors (chi2 = 81.000, p < 0.01). With regards to the distribution of HCV-positivity according to blood group, 4.1% of the O RhD-positive subjects, 10% of the A RhD-positive subjects and 25% of the AB RhD-positive were HCV-positive. No cases of HCV-positivity were found among the donors with other blood groups. No statistically significant relationship was found to exist between blood groups and HCV prevalence (p > 0.05). There was a moderate prevalence of HCV infection (5%) in apparently healthy blood donors in Port Hartcourt, Nigeria. The prevalence was higher among commercial donors and in donors in the age bracket of 21-30 years of age.


Clinical evaluation of a new two-site assay for CA125 antigen.
As appropriate surgery and chemotherapy can improve both quality of life and survival of patients with ovarian adenocarcinoma, there has been a pressing need for "serodiagnostic" assays to enable close patient monitoring. CA 125 antigen has previously been described as a useful tumor marker of ovarian cancer. This is the first clinical evaluation of a radioimmunoassay using two new monoclonal antibodies, B27.1 and B43.13, that react with separate sites on the glycoprotein marker CA 125. Using the new assay, the majority of patients with clinically or radiologically detectable disease had serum CA 125 antigen levels well above the upper limit seen with random apparently healthy donors, while only three patients who were believed free of disease had elevated levels. Disease progression was associated with increasing values of serum CA 125 antigen, while response to therapy was associated with a steady decline in serum CA 125 antigen levels. Seven patients had steadily rising serum CA 125 antigen levels after initially having normal levels. The mean lead time between rise above normal and clinical or radiological evidence of relapse was 5 months (range 2 to 12 months). The merits of further surgical intervention are illustrated by the serial values of two patients followed after chemotherapy. The assay appears to have value in monitoring response to therapy and in detecting disease relapse at a time when appropriate therapeutic intervention is still possible or likely to be beneficial. Furthermore, monitoring CA 125 antigen was shown to be of benefit in assessing response to chemotherapy in a few patients with metastatic adenocarcinoma of unknown primary, and may be useful in this group of patients in determining those likely to benefit from aggressive chemotherapy.


Feasibility of transoral robotic-assisted high-resolution microendoscopic imaging of oropharyngeal squamous cell carcinoma.
Transoral robotic-assisted oncologic surgery of the head and neck offers promising functional results. Nonetheless, the efficacy of oncologic surgery remains critically dependent on obtaining negative margins. We aimed to integrate a miniaturized high-resolution fiber-optic microendoscope (HRME), which provides real-time histological assessment, with the da Vinci robotic system (Intuitive Surgical, Sunnyvale, CA). Three patients undergoing transoral robotic surgery (TORS) were prospectively enrolled in this study. Optical imaging of the oropharynx was performed intraoperatively with the robotic-assisted HRME. All patients underwent the procedure successfully with no complications. The HRME was successfully integrated with the da Vinci robotic system. Several sites of the oropharynx and associated malignancy were imaged, which correlated with the standard histopathological analysis. Transoral robotic-assisted HRME imaging of the oropharynx is a safe and technically feasible approach, providing a real-time histological assessment and may serve as a valuable aid in oncologic surgery.


Bone banking in Thailand. A 10-year experience (1984-1994).
The tissue bank of the Bangkok Biomaterial Center was initiated in Thailand in 1984, and the first 10 years of progress are summarized. Three hundred ninety-seven cadavers and sixteen living donors provided a total of 13,676 bone and soft tissue allografts. They were used by 134 surgeons in 44 hospitals. A total of 1178 patients were surgically treated (581 males and 486 females). There were 240 cases of deep-frozen bone allografts, 600 cases of freeze-dried bone allografts, and 338 cases of soft tissue allografts. The results for 1035 cases (95.3%) were normal, whereas the results for 51 cases (4.33%) showed complications.


Combined royal jelly 10-hydroxydecanoic acid and aspirin has a synergistic effect against memory deficit and neuroinflammation.
Alzheimer's disease (AD), the most common form of neurodegenerative dementia among the older population, is associated with acute or chronic inflammation. As a nonsteroidal anti-inflammatory drug, aspirin has recently been widely studied in the prevention and treatment of neurodegenerative diseases. However, there is a controversy about the efficacy as well as the adverse effects of aspirin. 10-Hydroxydecanoic acid (10-HDAA) is a characteristic fatty acid found in the honey bee product royal jelly. In this study, we found that 10-HDAA attenuated the activation of the NF-κB pathway, then targeted Ptgs-1/2, the well-known target of aspirin. Hence, combined therapy of 10-HDAA and aspirin was conducted. In vitro assays suggested that this combinatory group alleviated LPS-induced inflammation in BV-2 cells, as assessed by the downregulation of nitric oxide, COX-2, and IL-6 compared to 10-HDAA or aspirin treatment alone. In vivo assays showed that the combined treatment synergistically inhibited the overactivation of glial cells and decreased the levels of pro-inflammatory mediators. Moreover, 10-HDAA alleviated the adverse effects of aspirin on gastrointestinal injuries and microbiota dysbiosis. The Morris water maze test indicated that neither 10-HDAA nor aspirin effectively improved LPS-induced memory dysfunction, but the combined therapy showed synergistic effects. Altogether, our findings support 10-HDAA and aspirin combinatory therapy as the basis for future therapeutics for AD and other neuroinflammation-related diseases with minimal adverse effects.


Feasibility of fluorescence imaging at microdosing using a hybrid PSMA tracer during robot-assisted radical prostatectomy in a large animal model.
With the rise of prostate-specific membrane antigen (PSMA) radioguided surgery, which is performed using a microdosing regime, demand for visual target confirmation via fluorescence guidance is growing. While proven very effective for radiotracers, microdosing approaches the detection limit for fluorescence imaging. Thus, utility will be highly dependent on the tracer performance, the sensitivity of the fluorescence camera used, and the degree of background signal. Using a porcine model the ability to perform robot-assisted radical prostatectomy under fluorescence guidance using the bimodal or rather hybrid PSMA tracer (99mTc-EuK-(SO3)Cy5-mas3) was studied, while employing the tracer in a microdosing regime. This was followed by ex vivo evaluation in surgical specimens obtained from prostate cancer patients. T50% blood and T50% urine were reached at 85 min and 390 min, in, respectively, blood and urine. Surgical fluorescence imaging allowed visualization of the prostate gland based on the basal PSMA-expression in porcine prostate. Together, in vivo visualization of the prostate and urinary excretion suggests at least an interval of > 7 h between tracer administration and surgery. Confocal microscopy of excised tissues confirmed tracer uptake in kidney and prostate, which was confirmed with PSMA IHC. No fluorescence was detected in other excised tissues. Tumor identification based on ex vivo fluorescence imaging of human prostate cancer specimens correlated with PSMA IHC. Intraoperative PSMA-mediated fluorescence imaging with a microdosing approach was shown to be feasible. Furthermore, EuK-(SO3)Cy5-mas3 allowed tumor identification in human prostate samples, underlining the translational potential of this novel tracer. Trial registration Approval for use of biological material for research purposes was provided by the Translational Research Board of the Netherlands Cancer Institute-Antoni van Leeuwenhoek hospital (NKI-AvL) under reference IRBm19-273 (22/10/2019).


[Radiotherapy in tubal carcinomas].
Cancer of the fallopian tube is one of the rarest gynecological malignancies. The treatment of choice for this tumor is not well defined because of its very low incidence. The preferred primary treatment is surgical resection consisting of abdominal hysterectomy, bilateral salpingo-oophorectomy and omentectomy. The value and extent of adjuvant radiotherapy is unclear so far. This retrospective analysis shows the experience at our clinic, which will be discussed in comparison with the existing literature. From 1967 to 1994, 9 patients were treated at the Clinic and Polyclinic for Radiotherapy--Radio-Oncology of the University of Münster with adjuvant radiotherapy following surgery for carcinoma of the fallopian tube. The staging according to FIGO yielded 2/9 stage I, 4/9 stage II and 3/9 stage III patients. In 5/9 patients the tumor could be resected completely. In 3/9 cases the pelvis alone, in 5/9 cases the pelvis and para-aortal region were irradiated with doses ranging from 45 Gy to 50 Gy. In 1/9 cases the target volume comprised the whole abdomen. The treatment results were acquired retrospectively by analysis of the patients' records and inquiries among their general practitioners. Median survival of our patients was 25 months, 6/9 developed recurrence after a median time of 10.5 months. All of these were localized in the abdominal cavity; 1 patient also developed liver metastases. All patients with recurrent tumor died from their disease within a median period of 9 months. Of the other 3/9 patients, 2/3 died after 6 and 36 months, and 1 patient is still alive after 42 months; all of them without any sign of recurrence. Adjuvant radiotherapy of carcinoma of the fallopian tube seems to be indicated with the exception of little invasive tumors of FIGO stage I. From our findings, the target volume should comprise the whole abdomen. A smaller treatment volume (pelvis alone or plus the para-aortal region) can only be of any use in a palliative situation or as a salvage therapy.


[Clinicopathological study on low grade glioma. In relation to malignant transformation].
The clinical status of patients with glioma is influenced by 1) the histological malignancy of the tumor, 2) the tumor volume, 3) secondary status such as brain edema or intracranial hypertension due to the tumor, and 4) the host immunity. Due to some improvement in at least 2) and 3) by the initial treatment, most low grade glioma cases pass through a clinically silent postsurgical period. However, at a certain point, transition to a high grade tumor malignant transformation may occur with exacerbation of the symptoms. Twenty-two cases of histologically established low grade glioma experienced over the past 7 years, in which immunological status was evaluated, were analyzed. Nine cases (41%) showed malignant transformation. Characteristic pictures of the clinical symptoms, computed tomography (CT) scan findings, immunological status, and morphological findings (mainly immunohistochemical examination) in nine cases were delineated. The findings at the time of exacerbation of the symptoms were as follows. In all cases CT scan demonstrated the change in the main lesion from low density to mixed density and were compatible with a high grade glioma. Reduction in host immunity was verified. Morphological increase in the tumor volume, increase in histological malignancy and deterioration in the secondary status due to the tumor were confirmed. Necrosis of the tumor cells as well as increase in giant cells and gemistocytes were observed. Immunohistochemical analysis revealed a decrease and irregularity in glial fibrillary acidic protein positive cells and positive processes as well as increase in vimentin intensity. These findings demonstrate change in the biological characteristics of the tumor.(ABSTRACT TRUNCATED AT 250 WORDS)


Autoantibodies in HIV-infected patients: Cross site-specific hydrolysis of H1 histone and myelin basic protein.
Histones act as damage-associated molecules, while anti-DNA antibodies are directed against histone-DNA nucleosomal complexes. Myelin basic protein (MBP) plays an important role in the pathogenesis of multiple sclerosis. Autoantibodies (Abs) with enzymatic activities are the distinctive feature of some autoimmune and viral diseases. Abzymes with proteolytic activity against different proteins specifically hydrolyze only these specific proteins. Using chromatography of IgGs on columns with immobilized H1 histone and then by chromatography of the fraction having an affinity for the histone (eluted upon loading) on MBP Sepharose, the anti-MBP antibodies were obtained. Anti-H1 antibodies were obtained using these columns in reverse order. IgGs against H1 and MBP effectively hydrolyze both H1 histone and MBP but no other control proteins. Using the MALDI mass spectrometry, the cleavage sites of H1 histone and MBP by abzymes against these proteins are found. The hydrolysis of MBP by anti-MBP IgGs occurs at four clusters (22 sites of the hydrolysis) locating at four known antigenic determinants of MBP. Anti-H1 Abs hydrolyze MBP only at one cluster (11 sites of the hydrolysis); this cluster is only partially overlapped with one of the four MBP clusters. Anti-H1 antibodies hydrolyze H1 at five sites of one cluster of the protein when anti-MBP IgGs cleavage this histone at two clusters containing 17 sites of the cleavage. Anti-H1 and anti-MBP abzymes are the first examples of Abs possessing not only with cross-complexing but also with catalytic cross-reactivity. The existence of cross-reactivity of abzymes against histones and MBP represent great danger to humans. © 2018 BioFactors, 45(2):211-222, 2019.


Scleral and conjunctival hemorrhages arising from a gunshot wound of the chest: a case report.
A young man committed suicide in the back seat of an automobile, witnessed by two law enforcement officers sitting in the front seat who had attempted to dissuade him from killing himself over an eight hour period. Death was caused by a contact gunshot wound of the anterior chest, which entered the midsternum and disrupted the anterior right atrium and ventricle of the heart, without involvement of either left ventricle or atrium. At the autopsy, bilateral fresh, confluent scleral and conjunctival sulcus hemorrhages were discovered, with no other evidence of facial or intracranial trauma. These hemorrhages are postulated to have arisen from a sudden pressure wave ascending through the superior vena cava, in a manner similar to the ocular findings associated with the retrograde venous blood flow that occurs during severe thoracic compression. These hemorrhages should not be mistaken for evidence that a decedent was beaten or otherwise involved in an assault episode.


Perceptions of parenting as predictors of boys' sibling and peer relations.
This study included 71 target boys (8 to 10 years), their siblings, and mothers to examine the relations among mothering, fathering, sibling aggression, and peer outcomes. Siblings whose mothers were known to be more rejecting were observed and reported to be more aggressive with one another than siblings whose mothers were less rejecting. Moreover, boys who experienced more aggressive sibling interactions were more likely to be nominated by their peers as being aggressive and were less accepted by their peers. Although fathering failed to evince a direct influence on sibling aggression, an indirect effect was evidenced in that less accepting fathering related to more rejecting mothering. It appeared that boys' aggressive experiences with their siblings mediated, in part, the association between maternal rejection and their peer aggression and that peer aggression was a mediating link between sibling aggression and boys' acceptance by their peers.


The Mn cluster in the S(0) state of the oxygen-evolving complex of photosystem II studied by EXAFS spectroscopy: are there three Di-mu-oxo-bridged Mn(2) moieties in the tetranuclear Mn complex?
A key component required for an understanding of the mechanism of the evolution of molecular oxygen by the photosynthetic oxygen-evolving complex (OEC) in photosystem II (PS II) is the knowledge of the structures of the Mn cluster in the OEC in each of its intermediate redox states, or S-states. In this paper, we report the first detailed structural characterization using Mn extended X-ray absorption fine structure (EXAFS) spectroscopy of the Mn cluster of the OEC in the S(0) state, which exists immediately after the release of molecular oxygen. On the basis of the EXAFS spectroscopic results, the most likely interpretation is that one of the di-mu-oxo-bridged Mn-Mn moieties in the OEC has increased in distance from 2.7 A in the dark-stable S(1) state to 2.85 A in the S(0) state. Furthermore, curve fitting of the distance heterogeneity present in the EXAFS data from the S(0) state leads to the intriguing possibility that three di-mu-oxo-bridged Mn-Mn moieties may exist in the OEC instead of the two di-mu-oxo-bridged Mn-Mn moieties that are widely used in proposed structural models for the OEC. This possibility is developed using novel structural models for the Mn cluster in the OEC which are consistent with the structural information available from EXAFS and the recent X-ray crystallographic structure of PS II at 3.8 A resolution.


Experimental study on intramuscular injection of eukaryotic expression vector pcDNA3- IL-6 on BXSB mice.
To study the role of IL-6 in systemic lupus erythematosis (SLE). We constructed eukaryotic expression vector pcDNA3- IL-6 encoding for IL-6 and injected it intramuscularly into BXSB mice. 22 of the 3.5-month-old male BXSB mice were divided into two groups. One group was injected with the pcDNA3-IL-6 100 micrograms per mouse twice at the interval of 20 days. Another group was injected with plasmid pcDNA3 at the same time as control. The ANA and proteinuria were monitored every 10 days, and the IL-6 activity in serum, IgG, C3 deposition and IL-6 expression in kidney detected at the 40th day. IL-6 encoding plasmid had harmful effects on murine SLE with increased ANA level, proteinuria, IgG, C3 deposition and IL-6 expression in kidney, but there was no difference of serum GPT levels between the two groups. Excessive production of IL-6 could play an important pathogenic role in SLE. Blocking or reducing IL-6 secretion might be a new therapy for SLE.


Real-time Virtual Sonography for navigation during targeted prostate biopsy using magnetic resonance imaging data.
To evaluate the effectiveness of the medical navigation technique, namely, Real-time Virtual Sonography (RVS), for targeted prostate biopsy. Eighty-five patients with suspected prostate cancer lesions using magnetic resonance imaging (MRI) were included in this study. All selected patients had at least one negative result on the previous transrectal biopsies. The acquired MRI volume data were loaded onto a personal computer installed with RVS software, which registers the volumes between MRI and real-time ultrasound data for real-time display. The registered MRI images were displayed adjacent to the ultrasonographic sagittal image on the same computer monitor. The suspected lesions on T2-weighted images were marked with a red circle. At first suspected lesions were biopsied transperineally under real-time navigation with RVS and then followed by the conventional transrectal and transperineal biopsy under spinal anesthesia. The median age of the patients was 69 years (56-84 years), and the prostate-specific antigen level and prostate volume were 9.9 ng/mL (4.0-34.2) and 37.2 mL (18-141), respectively. Prostate cancer was detected in 52 patients (61%). The biopsy specimens obtained using RVS revealed 45/52 patients (87%) positive for prostate cancer. A total of 192 biopsy cores were obtained using RVS. Sixty-two of these (32%) were positive for prostate cancer, whereas conventional random biopsy revealed cancer only in 75/833 (9%) cores (P < 0.01). Targeted prostate biopsy with RVS is very effective to diagnose lesions detected with MRI. This technique only requires additional computer and RVS software and thus is cost-effective. Therefore, RVS-guided prostate biopsy has great potential for better management of prostate cancer patients.


Plasma-assisted pretreatment of wheat straw.
O₃ generated in a plasma at atmospheric pressure and room temperature, fed with dried air (or oxygen-enriched dried air), has been used for the degradation of lignin in wheat straw to optimize the enzymatic hydrolysis and to get more fermentable sugars. A fixed bed reactor was used combined with a CO₂ detector and an online technique for O₃ measurement in the fed and exhaust gas allowing continuous measurement of the consumption of O₃. This rendered it possible for us to determine the progress of the pretreatment in real time (online analysis). The process time can be adjusted to produce wheat straw with desired lignin content because of the online analysis. The O₃ consumption of wheat straw and its polymeric components, i.e., cellulose, hemicellulose, and lignin, as well as a mixture of these, dry as well as with 50% water, were studied. Furthermore, the process parameters dry matter content and milled particle size (the extent to which the wheat straw was milled) were investigated and optimized. The developed methodology offered the advantage of a simple and relatively fast (0.5-2 h) pretreatment allowing a dry matter concentration of 45-60%. FTIR measurements did not suggest any structural effects on cellulose and hemicellulose by the O₃ treatment. The cost and the energy consumption for lignin degradation of 100 g of wheat straw were calculated.


Modified automatic R-peak detection algorithm for patients with epilepsy using a portable electrocardiogram recorder.
Earlier studies have shown that short term heart rate variability (HRV) analysis of ECG seems promising for detection of epileptic seizures. A precise and accurate automatic R-peak detection algorithm is a necessity in a real-time, continuous measurement of HRV, in a portable ECG device. We used the portable CE marked ePatch® heart monitor to record the ECG of 14 patients, who were enrolled in the videoEEG long term monitoring unit for clinical workup of epilepsy. Recordings of the first 7 patients were used as training set of data for the R-peak detection algorithm and the recordings of the last 7 patients (467.6 recording hours) were used to test the performance of the algorithm. We aimed to modify an existing QRS-detection algorithm to a more precise R-peak detection algorithm to avoid the possible jitter Qand S-peaks can create in the tachogram, which causes error in short-term HRVanalysis. The proposed R-peak detection algorithm showed a high sensitivity (Se = 99.979%) and positive predictive value (P+ = 99.976%), which was comparable with a previously published QRS-detection algorithm for the ePatch® ECG device, when testing the same dataset. The novel R-peak detection algorithm designed to avoid jitter has very high sensitivity and specificity and thus is a suitable tool for a robust, fast, real-time HRV-analysis in patients with epilepsy, creating the possibility for real-time seizure detection for these patients.


Bone regeneration with resorbable polymeric membranes. III. Effect of poly(L-lactide) membrane pore size on the bone healing process in large defects.
Poly(L-lactide) membranes of various pore sizes: microporous, medium pore size (10-20 microns), and large pore size (20-200 microns) were implanted in 15 mature New Zealand female rabbits to cover a 10-mm diaphyseal defect created in the radius. Five rabbits were implanted with each membrane. No internal fixation was used, as it was assumed that the intact ulna splints the radius adequately. Postoperative radiographs revealed the formation of hematoma within the bone defect. At the 2nd week after surgery, the hematoma was resorbed and the formation of new bone was noted radiologically either at the ends of the bone fragments or as osteophytes on the proximal and distal edges of the membrane. At 4 weeks, the newly formed bone was growing centripetally from the fragment ends. The bone regeneration took place in the majority of the cases under investigation, regardless of the pore size of the polymeric membranes used. There were, however, some differences in the intensity of the bone regeneration process. Although at 2 weeks after surgery bone formation was seen radiographically in all animals, at 6 months five rabbits of five, four rabbits of five, and three rabbits of five implanted respectively with microporous membrane, medium pore-size membrane, and large pore-size membrane showed complete regeneration of bone within the defects. It is suggested that the primary function of the membrane used to cover bone defects is to preserve the osteogenic components present in the space under the membrane from escaping and support the growth of cells within the "medullary cavity" formed by the tubular implant.


Ontogeny of the visual system in the cuttlefish, Sepiella japonica. I. Morphological differentiation of the visual cell.
To provide morphological bases for functional studies, the differentiation of photoreceptors in the retina of a cuttlefish, Sepiella japonica, was examined by electron microscopy. Development of the retina occurs in four phases. In phase 1 (stages 21-23), the retinal epithelium consists of uniform columnar cells. In phase 2 (stages 24-29), the epithelial cells are classified into light and dark cells on the basis of the electron-density of their cytoplasm. The perikarya of the light cells are located in the distal half of the epithelium, each extending proximally (i.e., sclerad) a thin foot, which protruded out of the epithelium through a narrow break in the basal lamina. The nuclei of the dark cells are distributed in the proximal half of the epithelium. Both cell types have a short cilium in the distal end. In phase 3 (stages 30-35), the light and the dark cells morphologically differentiate into receptor and supporting cells, respectively. The distal end of the light (receptor) cell begins to form an apical process, which gives off short irregular microvilli from its lateral surface. Beneath the basal lamina the feet of the receptor cells swell and the nuclei migrate into them through narrow breaks in the basal lamina. Thus, at the end of phase 3, each receptor cell becomes divided into an outer and inner segment. In phase 4 (stages 36-40), the receptor cells complete the specific structure as photoreceptive cells. The microvilli arising from the apical processes increase in length, density, and regularity to be organized into rhabdomes. The lamellated membranes of the myeloid bodies appear first in the outer segment and later increase in number in the inner segment. Morphometric data on the rhabdomeric microvilli in the adult and embryonic retinas are presented.


NAFLD or MAFLD: Which Has Closer Association With All-Cause and Cause-Specific Mortality?-Results From NHANES III.
Background: The recent change of terminology from non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated fatty liver disease (MAFLD) has raised heated discussion. We aim to investigate the association of MAFLD or NAFLD with all-cause and cause-specific mortality to compare the outcomes of the two diagnostic criteria in population-based study. Methods: We recruited 12,480 participants from the Third National Health and Nutrition Examination Survey (NHANES III) with matched mortality data in 2015. Participants were divided into four groups for survival analysis: without NAFLD or MAFLD, with only NAFLD, only MAFLD. Cox proportional hazard regression was used to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality. Subgroup analysis were applied in MAFLD patients. Results: The weighted prevalence of MAFLD and NAFLD was relatively 27.4 and 27.9%. Participants with NAFLD or MAFLD were largely overlapped (weighted Cohen's kappa coefficient 0.76). MAFLD increased the overall risk for total mortality in a greater magnitude than NAFLD [HR 2.07 (95% CI 1.86, 2.29) vs. 1.47 (1.20, 1.79)], However, the difference was non-significant after metabolic parameters were adjusted. Risks for cardiovascular, neoplasm, and diabetes-related mortality were similar between MAFLD and NAFLD. Referring to individuals without both NAFLD and MAFLD, individuals with only NAFLD showed reduced total mortality [HR 0.48 (0.34, 0.68)] and neoplasm mortality [HR 0.46 (0.24, 0.89)] in crude. Nevertheless, individuals with only MAFLD independently increased the risk for total mortality [adjusted HR 1.47 (1.22, 1.77)] and neoplasm mortality [aHR 1.58 (1.09, 2.28)]. The risk for overall mortality in MAFLD was consistent between subgroups except for race-ethnicity and whether secondary to viral hepatitis. Conclusions: Participants with MAFLD or NAFLD were highly concordant. MAFLD showed greater risk for all-cause mortality and equal risk for cause-specific mortality referring to NAFLD. The new terminology excluded participants with lower mortality risk and included participants with higher risk. Drug development for MAFLD should consider ethnic differences.


An unusual Neisseria isolated from conjunctival cultures in rural Egypt.
Seven isolates of an unusual Neisseria sp. were obtained from eye cultures of children in two rural Egyptian villages. These Neisseria utilized only glucose, they exhibited a positive reaction when tested with antisera to crude antigen from Neisseria meningitidis and N. gonorrhoeae, and they did not react with the fluorescent antibody tests for N. gonorrhoeae or with the monoclonal antibodies used to serotype gonococci. The Egyptian isolates had colony morphology more typical of meningococci than gonococci and showed opaque and transparent colony variants. On SDS-PAGE, the major outer-membrane proteins had different patterns than those noted for comparable proteins of meningococci and gonococci; heat-modifiable outer-membrane proteins were present. Four of the six isolates examined had cryptic plasmids of 2.8 megadaltons, which were slightly larger than the cryptic plasmid of N. gonorrhoeae. These plasmids were homologous to the gonococcal cryptic plasmid, but had different restriction enzyme fragment patterns. The DNA from the Egyptian isolates, like DNA from N. meningitidis but unlike DNA from N. gonorrhoeae, could be cut with the restriction enzyme HaeIII. The frequency of transformation into a temperature-sensitive mutant of N. gonorrhoeae was 0.2 for the Egyptian isolates and 0.1 for N. meningitidis, a frequency that was 5-10-fold lower than that for the N. gonorrhoeae control isolates. Whole-cell DNA from the Egyptian isolates showed 68%-73% homology with N. gonorrhoeae and 57%-63% with N. meningitidis. On the basis of our observations, the Egyptian isolates are distinct from N. meningitidis and may represent a variant of N. gonorrhoeae. We suggest that the isolates be called Neisseria gonorrhoeae ssp. kochii.


[Two patients of recurrent breast cancer with carcinomatous pleurisy well controlled pleural effusion].
We report two patients of recurrent breast cancer with carcinomatous pleurisy well controlled pleural effusion. One patient is a 49-year-old woman. She underwent radical mastectomy for right breast cancer in September 1993. She suffered from multiple liver metastases in June 2000, so CEF therapy contained hepatic arterial infusion chemotherapy and extended right lobectomy of the liver were performed in December 2001. Right pleural effusion was detected in December 2003, then, pleurodesis was carried out with OK-432 after thoracic drainage. After pleurodesis, a weekly paclitaxel therapy was started and she was taking the regimen continuously. Another patient is a 55-year-old woman. She underwent radical mastectomy for left breast cancer in September 1999. Local recurrent lesions on the left chest and left pleural effusion were found in May 2003. After thoracic drainage, infectious pleurisy was complicated, so the drainage tube was removed after the therapy for preventing infection. After pleurodesis, CE therapy followed by peroral chemo-endocrine therapy was performed. Both of the two patients are receiving outpatient treatment without recurrent pleural effusion as of July 2005.


Gender difference in hepatic steatosis index and lipid accumulation product ability to predict incident metabolic syndrome in the historical cohort of the Brisighella Heart Study.
Abstract Background: Nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome are strongly related from both an epidemiological and a pathological point of view. The main aim of our study was to evaluate if two validated indexes of NAFLD are able to predict the 4-year metabolic syndrome incidence in a large population sample of pharmacologically untreated subjects without metabolic syndrome, type 2 diabetes, history of alcohol abuse, or known liver diseases at the baseline. From the database of the Brisighella Heart Study, we selected a subsample of 824 pharmacologically untreated subjects (male, 401; female, 423) without metabolic syndrome, type 2 diabetes, alcohol abuse, or known liver diseases at the 2004 survey and revisited in 2008. The Hepatic Steatosis Index (HSI) and Lipid Accumulation Product (LAP) values were calculated for everyone to evaluate their predictive role for metabolic syndrome through a Cox-regression analysis adjusted by metabolic syndrome components. We observed 46 new cases of metabolic syndrome (male, 25; female, 21) with a cumulative incidence of 5.6% (1.4% per year): 6.2% in men (1.5% per year), 4.9% in women (1.2% per year). In women, the 4-year metabolic syndrome predictors (R(2)=0.680) were age [odds ratio (OR) 1.13, 95% confidence interval (CI) 1.12-1.15], HSI (OR 1.20, 95% CI 1.15-1.26), and lnLAP (OR 1.16, 95% CI 1.14-1.17), whereas in men they were (R(2)=0.554) age (OR 1.13, 95% CI 1.11-1.14) and lnLAP (OR 1.17, 95% CI 1.15-1.18). HSI and LAP differently predict the 4-year incidence of metabolic syndrome. In women, both indexes can be considered significant predictors, whereas in men only LAP can be considered predictive.


"Jianbing" styling multifunctional electrospinning composite membranes for wound healing.
Wound infection and excessive exudate can affect the process of wound healing. However, the disadvantage of the anti-microbial wound dressings is that the biological fluids are ineffectively removed. Inspired by making "Chinese Jianbing", a composite wound nano-dressing was developed consisting of a hydrophilic outer layer (chitosan&polyvinyl alcohol: CTS-PVA) and a hydrophobic inner layer (propolis&polycaprolactone: PRO-PCL) by combining casting and electrospinning methods for effective antibacterial and unidirectional removing excess biofluids. In vitro, the composite wound nano-dressing of PRO-PCL and CTS-PVA (PPCP) could strongly inhibit Pseudomonas aeruginosa. Furthermore, PPCP wound dressing had excellent antioxidant properties and blood coagulation index for effective hemostatic. Importantly, it had a preferable water absorption for removing excess biofluid. In vivo, it had anti-inflammatory properties and promoted collagen Ⅰ preparation, which realized 80% wound healing on day 7. In short, the PPCP wound dressing provides a new direction and option for antibacterial and removes excess biofluid.


Intra-atrial re-entrant tachycardia in patients with congenital heart disease: factors associated with disease severity.
Intra-atrial re-entrant tachycardia (IART) is a common complication in patients with congenital heart disease (CHD) and is related to increased morbidity and mortality. Few reports have been published about factors associated to IART severity. The aim of this study is to analyse factors associated to severe clinical presentation of IART. Observational study of all consecutive CHD patients who underwent a first IART ablation from January 2009 to December 2015 (94 patients, 39.4% female, and age: 36.55 ± 14.9 years). Severe clinical presentation was defined as heart failure, syncope, shock, electromechanical dissociation (EMD), or aborted sudden death. The majority of patients had moderately or highly complex cardiac defect (90.4%). Types of IART included cavotricuspid isthmus(CTI) dependent in 51% (48), non-CTI-related in 22.3% (20), and both types in 27.7% (26). In 38 patients (40.4%), a severe event occurred and in 16 (17%), the symptoms included shock, syncope, sudden death, or EMD. In 21 (22.3%), severe symptoms were the first manifestation of IART. In multivariate analysis, transposition of the great arteries (TGA) with right systemic ventricle (OR 5.32, 95% C.I. 1.6-7.02, P = 0.0005) and severe dilation of the venous atrium (VsA) (OR 4.17; 95% CI 1.4-8.12, P = 0.0009) were factors independently associated with severity. In our series of 94 CHD patients with a high proportion of moderately to highly complex cardiac defects, severe consequences of IART were frequent. Transposition of the great arteries with systemic right ventricle and severe dilation of VsA were independently associated to severity. Early invasive procedures should be considered for these high-risk patients.


Social Needs Resource Connections: A Systematic Review of Barriers, Facilitators, and Evaluation.
Healthcare organizations increasingly are screening patients for social needs (e.g., food, housing) and referring them to community resources. This systematic mixed studies review assesses how studies evaluate social needs resource connections and identifies patient- and caregiver-reported factors that may inhibit or facilitate resource connections. Investigators searched PubMed and CINAHL for articles published from October 2015 to December 2020 and used dual review to determine inclusion based on a priori selection criteria. Data related to study design, setting, population of interest, intervention, and outcomes were abstracted. Articles' quality was assessed using the Mixed Methods Appraisal Tool. Data analysis was conducted in 2021. The search identified 34 articles from 32 studies. The authors created a taxonomy of quantitative resource connection measures with 4 categories: whether participants made contact with resources, received resources, had their social needs addressed, or rated some aspect of their experience with resources. Barriers to resource connections were inadequacy, irrelevancy, or restrictiveness; inaccessibility; fears surrounding stigma or discrimination; and factors related to staff training and resource information sharing. Facilitators were referrals' relevancy, the degree of support and simplicity embedded within the interventions, and interventions being comprehensive and inclusive. This synthesis of barriers and facilitators indicates areas where healthcare organizations may have agency to improve the efficacy of social needs screening and referral interventions. The authors also recommend that resource connection measures be explicitly defined and focus on whether participants received new resources and whether their social needs were addressed.


Liver disease in cystic fibrosis: an update.
Cystic fibrosis (CF) is the most widespread autosomal recessive genetic disorder that limits life expectation amongst the Caucasian population. As the median survival has increased related to early multidisciplinary intervention, other manifestations of CF have emerged especially for the broad spectrum of hepatobiliary involvement. The present study reviews the existing literature on liver disease in cystic fibrosis and describes the key issues for an adequate clinical evaluation and management of patients, with a focus on the pathogenetic, clinical and diagnostic-therapeutic aspects of liver disease in CF. A literature search of electronic databases was undertaken for relevant studies published from 1990 about liver disease in cystic fibrosis. The databases searched were: EMBASE, PubMed and Cochrane Library. CF is due to mutations in the gene on chromosome 7 that encodes an amino acidic polypeptide named CFTR (cystic fibrosis transmembrane regulator). The hepatic manifestations include particular changes referring to the basic CFTR defect, iatrogenic lesions or consequences of the multisystem disease. Even though hepatobiliary disease is the most common non-pulmonary cause of mortality in CF (the third after pulmonary disease and transplant complications), only about the 33%of CF patients presents clinically significant hepatobiliary disease. Liver disease will have a growing impact on survival and quality of life of cystic fibrosis patients because a longer life expectancy and for this it is important its early recognition and a correct clinical management aimed at delaying the onset of complications. This review could represent an opportunity to encourage researchers to better investigate genotype-phenotype correlation associated with the development of cystic fibrosis liver disease, especially for non-CFTR genetic polymorphisms, and detect predisposed individuals. Therapeutic trials are needed to find strategies of fibrosis prevention and to avoid its progression prior to development its related complications.


Academy begins search for operational model.
Very much in vogue these days is discussion of the tensions between quality and costs in the delivery of health care services. A recurring problem, however, is the absence of any clear definition of exactly how quality and cost are interrelated. The beginnings of a model for that definition were presented at one of the courses at this year's National Institute on Health Care Leadership and Management in Point Clear, Ala.


Specific proteolysis of human plasminogen by a 24 kDa endopeptidase from a novel Chryseobacterium Sp.
A novel single polypeptide endopeptidase of 24 kDa (24k-endopeptidase) was purified with a yield of 300-400 microg/L from conditioned medium of a bacterial strain which was identified as a new species in the genus Chryseobacterium Sp. on the basis of its 16S rDNA sequence and DNA:DNA hybridizations. The NH(2)-terminal amino acid sequence (Val-Ala-Thr-Pro-Asn-Leu-Glu-.) was not found in the availabe databases. The 24k-endopeptidase specifically hydrolyzed the Ser(441)-Val(442) peptide bond in human plasmin(ogen), with additional cleavage of the Lys(78)-Val(79) and Pro(447)-Val(448) peptide bonds, and a secondary cleavage at Lys(615)-Val(616). Thereby, plasminogen is converted into an angiostatin-like fragment containing kringles 1-4 (K1-4) and miniplasminogen (kringle 5 and the serine proteinase domain). The purified K1-4 fragment showed a comparable cytotoxicity toward endothelial cells as the elastase-derived K1-3 fragment (12.7% versus 10.6% at a concentration of 10 microg/mL). Plasminogen, bound to monocytoid THP-1 cells, was also cleaved by the 24k-endopeptidase, resulting in generation of an angiostatin-like fragment and in a decreased capacity to generate cell-associated plasmin following activation by urokinase. The 24k-endopeptidase was not efficiently neutralized by specific inhibitors against the serine, cysteine, aspartic, or matrix metalloproteinase classes of enzymes. In human plasma or serum, however, it induced only very limited plasminogen degradation, apparently due to neutralization of its activity by alpha(2)-macroglobulin. Interaction of this novel 24k-endopeptidase with plasminogen thus yields an angiostatin-like fragment and affects plasmin-mediated cellular proteolytic activity.


Burned out or "just" depressed? An existential phenomenological exploration of burnout.
An increasing number of patients are on sick leave from work due to fatigue- and pain-related symptoms that could indicate burnout. The aetiology is unknown, and recently, it has been considered whether burnout should be a distinct medical diagnosis or "just" a form of depression. Little attention has been given to these individuals' experiences. Therefore, we conducted a phenomenological study to explore burnout from a first person perspective. The aim of the study was to obtain a deeper understanding of burnout as phenomenon. We are inspired by Merleau-Ponty's phenomenological approach and gestalt theory. The phenomenological focus is to attend to the embodied consciousness of the lived experience of being human. An interpretative phenomenological analysis (IPA) was chosen to uncover how the interviewees made meaning of their situation. Six individuals who had been on sick leave at 50% to 100% for at least 3 months due to fatigue- and pain-related symptoms were interviewed. Four narrative phases mirroring burnout as a temporal sequence stood out: achievement, pressure, psychosomatic collapse, and personal meaning and reorientation. We identified several interruptions to contact, which seemed to boost the interviewees' ability to continue striving beyond their limits. The results of this study contribute to a deeper understanding of how complex factors might influence individual vulnerability and lead to a fatigue reaction. The findings indicate that lack of recognition of the interviewees' illness may have affected the healing process. When understanding burnout as an intersubjective, lived, contextual, and temporal experience, it is important to take the implications of such factors into consideration for both medical theory and clinical practice. On the basis of our findings, we argue that reducing burnout to a form of depression will neither solve the problem of its unknown aetiology nor provide for meaningful individual health care.


Spatial and temporal evolution of quantitative magnetic resonance imaging parameters of peach and apple fruit - relationship with biophysical and metabolic traits.
Fruits are complex organs that are spatially regulated during development. Limited phenotyping capacity at cell and tissue levels is one of the main obstacles to our understanding of the coordinated regulation of the processes involved in fruit growth and quality. In this study, the spatial evolution of biophysical and metabolic traits of peach and apple fruit was investigated during fruit development. In parallel, the multi-exponential relaxation times and apparent microporosity were assessed by quantitative magnetic resonance imaging (MRI). The aim was to identify the possible relationships between MRI parameters and variations in the structure and composition of fruit tissues during development so that transverse relaxation could be proposed as a biomarker for the assessment of the structural and functional evolution of fruit tissues during growth. The study provides species-specific data on developmental and spatial variations in density, cell number and size distribution, insoluble and soluble compound accumulation and osmotic and water potential in the fruit mesocarp. Magnetic resonance imaging was able to capture tissue evolution and the development of pericarp heterogeneity by accessing information on cell expansion, water status and distribution at cell level, and microporosity. Changes in vacuole-related transverse relaxation rates were mostly explained by cell/vacuole size. The impact of cell solute composition, microporosity and membrane permeability on relaxation times is also discussed. The results demonstrate the usefulness of MRI as a tool to phenotype fruits and to access important physiological data during development, including information on spatial variability.


Long-Lived Local Triplet Excited State and Charge Transfer State of 4,4'-Dimethoxy Triphenylamine-BODIPY Compact Electron Donor/Acceptor Dyads.
The spin-orbit charge transfer intersystem crossing (SOCT-ISC) and the formation of a long-lived charge transfer (CT) state were studied with a series of 4,4'-dimethoxy triphenylamine-BODIPY compact electron donor/acceptor dyads. Different torsion freedoms were applied in the dyads to tune the electronic coupling between the donor and acceptor, and a red-shifted CT absorption band was observed for one dyad. The dyads show solvent polarity-dependent singlet oxygen photosensitizing ability (quantum yields 3%-79%). Nanosecond transient absorption spectra of the dyad in nonpolar solvent confirm the formation of triplet states. The intrinsic triplet state lifetime is up to 383 μs (in fluid solution), which is much longer than that accessed with the heavy atom effect (276 μs). Intermolecular triplet photosensitizing of the dyads in a polar solvent produces a long-lived 3CT state (lifetime, τCT = 8.0 μs supported by the electron spin density surface analysis). The triplet state lifetime of the dyads doped in a Clear Flex 50 polymer film is exceptionally long (7.6-11.4 ms), and formation of a long-lived CT state (37 μs) was observed. Triplet-triplet annihilation upconversion was performed with the electron donor/acceptor dyads used as the triplet photosensitizer and perylene used as the triplet acceptor; the upconversion quantum yield is up to 15.8%.


Red blood cell transfusions and potentially related morbidities in neonates under 32 weeks' gestation.
Preterm neonates are likely to require red blood cell (RBC) transfusion, and extremely low birth weight infants almost invariably receive multiple transfusions. Transfusion-reduction strategies can reduce transfusion rates, and might diminish certain adverse outcomes associated with transfusions. In a single centre, we retrospectively evaluated RBC transfusion rates among preterm infants ≤32 weeks' gestational age (GA), over a 6-year period before and after adopting national transfusion-reduction strategies. We compared demographic data, adverse events, and outcomes between transfused vs not-transfused neonates. Univariate logistic regression was used to evaluate associations between dichotomous outcomes and number of transfusions, and day of first transfusion. Multivariate logistic regression evaluated the correlation between dichotomous outcomes and transfusion as an independent risk factor. During the 6 years studied, 181 infants born at ≤32 weeks' GA were admitted to our Neonatal Intensive Care Unit of whom 80 (44%) received at least one RBC transfusion. The transfusion rate tended downwards after adopting transfusion-reduction strategies, reaching 31% in 2018. The reduction was largely due to a marked fall in transfusions of neonates born at 29-32 weeks' GA (p<0.001). The number of transfusions received correlated with odds of having intraventricular haemorrhage (IVH) (OR=1.9; 95% CI: 1.3-2.7; p=0.0001) and the duration of oxygen supplementation (rho=0.51; 95% CI: 0.33-0.66; p≤0.0001). In multivariate logistic regression analysis, transfusion was an independent risk factor for IVH (adjusted OR=7.38; 95% CI: 2.24-24.30; p=0.0001). The application of national, standardised transfusion-reduction strategies was associated with a lower transfusion rate in neonates born at 29-32 weeks' GA, but was less effective among neonates ≤28 weeks, in whom transfusions appeared to be an independent risk factor for severe IVH.


Models for evaluating the pharmacokinetics and pharmacodynamics for β-blockers.
β-blocker therapy plays an important role in the treatment of various diseases, including hypertension, myocardial infarction and heart failure. Although all β-blockers shared their ability to competitively block β1-adrenoceptor, this therapeutic class showed great heterogeneity in their pharmacokinetic (PK) and pharmacodynamic (PD) properties. The present review describes the models used for PK and PK/PD evaluation of β-blockers and their applicability in preclinical and clinical studies. PK behavior of different β-blockers has been studied by means of individual compartmental and population PKs, allowing the estimation of relevant PK parameters and factors involved in intersubject variability. Different PK/PD models have been developed for the in vivo estimation of PD parameters of different cardiovascular effects of β-blockers. PK models and PK/PD modeling have clearly contributed to characterization of the PK and PD properties of β-blockers. Differences in cardiovascular actions between classical β-blockers and vasodilatory β-blockers need to be further studied in order to confirm the clinical benefits of the new-generation of β-blockers. PK/PD modeling may contribute to clarify the importance of heterogeneity of PK and PD properties of β-blockers potentially improving the selection of the adequate agent and dose regimen in the treatment of cardiovascular diseases.


Social variation in attitudes to obesity in children.
To evaluate variations in children's attitudes to obesity in relation to age, gender and social class. Evaluation of sex, age and social class differences in judgements of figure drawings varying in body shape. 180 children aged from 4-11 from six schools, varying in the social background of their pupils. Self ratings of body shape, choices of ideal body shape now and in adulthood from a range of line drawings of figures varying in fatness, and behavioural and personality stereotype judgements of illustrations of thin, average and fat children. Few children in this age group were fat and few felt too fat; though a substantial minority felt too thin. Girls selected thinner ideal figures than boys. Children demonstrated strongly negative attitudes to obesity, which were less favourable among those who were older and from the higher social status schools. There are significant social variations in attitudes to obesity which might be important in understanding variations in the prevalence of obesity and weight control practices.


Distribution of the feline lungworm Aelurostrongylus abstrusus in the USA based on fecal testing.
The aim of this study was to compile commercial reference laboratory data over a 10-year period to determine the distribution of Aelurostrongylus abstrusus, commonly known as feline lungworm, within the USA based on widespread fecal testing in cats. The results of 3,610,455 feline ova and parasite (O&P) zinc sulfate centrifugation fecal flotation tests performed at IDEXX Reference Laboratories in the USA from January 2008 to December 2017 were compiled and sorted for tests positive for A abstrusus larvae. The results of 3625 Baermann tests, currently considered the gold standard diagnostic for feline lungworm, were also retrieved from the same period. Of the tests performed, 4721 (0.13%) feline O&P zinc sulfate centrifugation fecal flotation tests and 75 (2.07%) of the Baermann tests conducted were positive for the presence of A abstrusus larvae. The O&P data revealed a significant association between infection status and sex, while male cats in both the O&P and Baermann data sets had a higher risk of A abstrusus infection than females. Significant variation in positive rates were observed by region and most positive cases were clustered in the Northeast, Midwest and West regions of the USA. This study highlights the distribution of feline lungworm in the USA and the limitations of using current testing to diagnose this infection. The introduction of higher throughput, less labor-intensive diagnostic methods could help increase awareness of this parasite among veterinary professionals, achieve a greater understanding of epidemiological factors, and improve the care and treatment for clinically ill feline patients.


Micro cell vesicle technology (mCVT): a novel hybrid system of gene delivery for hard-to-transfect (HTT) cells.
A hybrid gene delivery platform, micro Cell Vesicle Technology (mCVT), produced from the fusion of plasma membranes and cationic lipids, is presently used to improve the transfection efficiency of hard-to-transfect (HTT) cells. The plasma membrane components of mCVTs impart specificity in cellular uptake and reduce cytotoxicity in the transfection process, while the cationic lipids complex with the genetic material and provide structural integrity to mCVTs.


The role of CD4+CD25+ regulatory T cells in macrophage-derived foam-cell formation.
Cluster of differentiation (CD)4+CD25+ regulatory T cells (Tregs) exert a suppressive activity on atherosclerosis, but the underlying mechanism remains unclear. Here, we investigated whether and how Tregs affect macrophages foam-cell formation. Tregs were isolated by magnetic cell sorting-column and analyzed by flow cytometry. Macrophages were cultured with or without Tregs in the presence of oxidized LDL (oxLDL) for 48 h to transform foam cells. After co-culture with Tregs, macrophages showed a decrease in lipid accumulation, which was accompanied by a significantly downregulated expression of CD36 and SRA but no obvious difference in ABCA1 expression. Tregs can inhibit the proinflammatory properties of macrophages and steer macrophage differentiation toward an anti-inflammatory cytokine producing phenotype. Mechanistic studies reveal that both cell-to-cell contact and soluble factors are required for Treg-mediated suppression on macrophage foam-cell formation. Cytokines, interleukin-10 (IL-10), and transforming growth factor-beta (TGF-beta) are the key factors for these suppressive functions.


The efficacy of a semi-resorbable membrane based on silk fibroin-Glycerol on bone regeneration in rabbit calvarial defects compared to a commercial collagen membrane.
Silk fibroin-glycerol-based membranes were fabricated and characterized for use as a self-maintaining and non-collapsible semi-resorbable membrane in guided bone regeneration. The study assessed the bone regeneration capacity of silk fibroin-glycerol-based membranes compared to a collagen membrane in 10-mm circular bilateral calvarial defects of 20 male New Zealand white rabbits. The animals were divided into two sets of time frames of 4 and 12 weeks and allocated into four groups (n = 5/group); an empty defect (E), a collagen membrane (Bio-Gide®; BG), a silk fibroin-glycerol-collagen membrane (SGC), and a silk fibroin-glycerol membrane (SG). The bone density (optical density, OD) from the 2D radiographs, tissue reaction from histological sections, new bone volume, and area from micro-CT and the histomorphometry were evaluated. The Mean OD of the E (34.49 ± 14.21%) and BG groups (35.71 ± 9.65%) at 12 weeks were higher than at 4 weeks, but the SGC (39.04 ± 7.94%) and SG (40.96 ± 9.25%) groups were lower at 4 weeks. The new bone volumes at 4 weeks of the SG (24.19 ± 1.35%) and SGC groups (24.19 ± 3.47%) were significantly higher than the BG group (16.93 ± 2.95%) but were not different from the E group (18.39±4.78%). At 12 weeks, the new bone volumes in the SGC (29.09 ± 3.81%), SG (29.11 ± 5.94%), and BG groups (26.26 ± 4.42%) were higher than in the E group (21.63 ± 5.81%) without statistical significance. Histological images in the SGC and SG groups showed slow biodegradation without a foreign body reaction. The new bone area at 4 weeks was lowest in BG (12.95 ± 5.44%), and the others were comparable. At 12 weeks, the new bone area in the E group (23.55±8.69%) was lower than the BG (31.42 ± 6.18%), SG (35.25 ± 13.92%), and SGC groups (36.35 ± 10.23%). Silk fibroin-glycerol-based membranes are semi-resorbable membranes that possess a self-maintaining property, have a barrier function without collapsing, and are successful in facilitating bone regeneration.


Chiral ionic liquid-mediated photochirogenesis. Enantiodifferentiating photocyclodimerization of 2-anthracenecarboxylic acid.
Enantiodifferentiating photocyclodimerization of 2-anthracenecarboxylic acid (AC-H) and its lithium salt (AC-Li) in chiral ionic liquid (CIL), (R)-1-(2,3-dihydroxypropyl)-3-methylimidazolium acetate {[(R)-GLYMI][AcO]}, gave a mixture of two head-to-tail (HT) and two head-to-head (HH) cyclodimers in HT/HH ratios of 1.3-1.7 (for AC-H) and 2.2-4.3 (for AC-Li) with low enantiomeric excesses (ee) of 0-3% for chiral syn-HT and anti-HH dimers. In contrast, irradiation of AC-H in an aqueous solution, containing cucurbit[8]uril (CB[8]) as a host and [(R)-GLYMI][AcO] or [(R)-GLYMI][Tf(2)N] as a modifier of CB portals, afforded the HH dimers in 91-99% selectivity, although the anti-HH dimer was totally racemic. Interestingly, irradiation of AC-H in a dichloromethane solution, containing [(R)-GLYMI][AcO] as a chiral template, led to the formation of the HH-dimers in 98% selectivity with chiral anti-HH dimer in -14% ee, presumably by the dual ligation of two ACs to a CIL through electrostatic and hydrogen-bonding interactions.


Borna disease in a dog in Japan.
Borna disease (BD) was diagnosed in a 3-year-old male Welsh corgi suffering from a severe and acute progressive disorder of the central nervous system. Histopathologically, neuronal lesions were characterized by a non-suppurative encephalomyelitis dominated by large perivascular cuffs consisting of lymphocytes, macrophages and plasma cells; also present were inflammatory cell infiltrates in the neural parenchyma, neuronophagia and focal gliosis. Strong immunolabelling with BD virus (BDV) p40 antibody was diffusely distributed in the cytoplasm of small and large neurons in areas of the brain with and without inflammatory changes, and also in the spinal cord. Positive hybridization signals with BDV p40 sense and antisense riboprobes were seen in the nucleus and cytoplasm of the neurons throughout the whole brain and spinal cord. BDV p24 RNA in formalin-fixed brain tissue was detected by reverse transcriptase (RT)-nested polymerase chain reaction (PCR). BDV p24 RNA-positive signals were detected in the temporal lobe. This is the first report of spontaneous canine BD in Japan.


Genetic consequences of climate change for northern plants.
Climate change will lead to loss of range for many species, and thus to loss of genetic diversity crucial for their long-term persistence. We analysed range-wide genetic diversity (amplified fragment length polymorphisms) in 9581 samples from 1200 populations of 27 northern plant species, to assess genetic consequences of range reduction and potential association with species traits. We used species distribution modelling (SDM, eight techniques, two global circulation models and two emission scenarios) to predict loss of range and genetic diversity by 2080. Loss of genetic diversity varied considerably among species, and this variation could be explained by dispersal adaptation (up to 57%) and by genetic differentiation among populations (F(ST); up to 61%). Herbs lacking adaptations for long-distance dispersal were estimated to lose genetic diversity at higher rate than dwarf shrubs adapted to long-distance dispersal. The expected range reduction in these 27 northern species was larger than reported for temperate plants, and all were predicted to lose genetic diversity according to at least one scenario. SDM combined with F(ST) estimates and/or with species trait information thus allows the prediction of species' vulnerability to climate change, aiding rational prioritization of conservation efforts.


Development of a new microtiter plate format for clinically relevant assays.
A new format for the microtiter plate-based assays was proposed. The novelty involves the use of disk-shaped inserts for immobilization of biological and chemical reagents. The internal opening of the disks allows measurements of the reactions by standard microtiter plate readers without any additional steps involving liquid handling. Ideally the plate end-users just have to add the sample and take the measurement without any need of multiple reagent additions or transfer of the liquid to a different plate. The novel assay format also allows handling of reagents which are not soluble in an aqueous environment. As a proof of concept we describe here several model reactions which are compatible with microtiter plate format, such as monitoring enzymatic reactions catalyzed by glucose oxidase (GOx) and urease, measurements of proteins by BCA assay, analysis of pH, and concentration of antioxidants. The "mix and match" approach in the disk-shape format allows multiplexing and could be particularly useful for high throughput screening. One of the potential application areas for this novel assay format could be in a multianalyte system for measurement of clinically relevant analytes in primary care.


Detection of protoporphyrin IX in envelope membranes of pea chloroplasts.
Envelope membranes were prepared from mature pea chloroplasts. The tetrapyrrole contents of envelope membranes were analysed. The envelope membranes of pea chloroplasts contained substantial amounts of protoporphyrin IX and trace amounts of Mg-protoporphyrin IX and its monoester in addition to protochlorophyllide. The protoporphyrin IX content of envelope membranes was 89.25 pmol (mg protein)(-1). Its content in pea envelope membrane was higher than that of protochlorophyllide. The proportion of monovinyl and divinyl forms of protochlorophyllide present in pea chloroplast envelope membrane was 3:7. The significance of the presence of protoporphyrin IX in the envelope membrane is discussed in relation to plastidic Chl biosynthesis.


Localisation and regulation of the eIF4E-binding protein 4E-BP3.
The cap-binding protein eIF4E-binding protein 3 (4E-BP3) was identified some years ago, but its properties have not been investigated in detail. In this report, we investigated the regulation and localisation of 4E-BP3. We show that 4E-BP3 is present in the nucleus as well as in the cytoplasm in primary T cells, HEK293 cells and HeLa cells. 4E-BP3 was associated with eIF4E in both cell compartments. Furthermore, 4E-BP3/eIF4E association in the cytoplasm was regulated by serum or interleukin-2 starvation in the different cell types. Rapamycin did not affect the association of eIF4E with 4E-BP3 in the cytoplasm or in the nucleus.


A pilot study of implantable cardiac device interrogation by emergency department personnel.
Implanted devices (eg, pacemakers and defibrillators) provide valuable information and may be interrogated to obtain diagnostic information and to direct management. During admission to an emergency department (ED), significant time and cost are spent waiting for device manufacturer representatives or cardiologists to access the data. If ED personnel could safely interrogate implanted devices, more rapid disposition could occur, thus leading to potentially better outcomes at a reduced cost. This was a pilot study examining the feasibility of ED device interrogation. This was a prospective convenience sample study of patients presenting to the ED with any chief complaint and who had an implantable device capable of being interrogated by a Medtronic reader. After obtaining informed consent, study patients underwent device interrogation by ED research personnel. After reviewing the device data, the physician documented their opinions of the value of data in aiding care. Patients were followed up at intervals ranging from 30 days out to 1 year to determine adverse events relating to interrogation. Forty-four patients underwent device interrogation. Their mean age was 56 ± 14.7 years (range, 28-83), 75% (33/44) were male and 75% (33/44) were hospitalized from the ED. The interrogations took less than 10 minutes 89% of the time. In 60% of the cases, ED physicians reported the data-assisted patient care. No adverse events were reported relating to the ED interrogations. In this pilot study, we found that ED personnel can safely and quickly interrogate implantable devices to obtain potentially useful clinical data.


Molecular genotyping of Toxoplasma gondii from Central and South America revealed high diversity within and between populations.
Recent population studies revealed that a few major clonal lineages of Toxoplasma gondii dominate in different geographical regions. The Type II and III lineages are widespread in all continents and dominate in Europe, Africa and North America. In addition, the type 12 lineage is the most common type in wildlife in North America, the Africa 1 and 3 are among the major types in Africa, and ToxoDB PCR-RFLP #9 is the major type in China. Overall the T. gondii strains are more diverse in South America than any other regions. Here, we analyzed 164 T. gondii isolates from three countries in Central America (Guatemala, Nicaragua, Costa Rica), from one country in Caribbean (Grenada) and five countries from South America (Venezuela, Colombia, Peru, Chile, and Argentina). The multilocous polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) based genotyping of 11 polymorphic markers (SAG1, SAG2, alt.SAG2, SAG3, BTUB, GRA6, L358, PK1, C22-8, C29-2 and Apico) were applied to 148 free-range chicken (Gallus domesticus) isolates and 16 isolates from domestic cats (Felis catus) in Colombia; 42 genotypes were identified. Linkage disequilibrium analysis indicated more frequent genetic recombination in populations of Nicaragua and Colombia, and to a lesser degree in populations of Costa Rica and Argentina. Bayesian structural analysis identified at least three genetic clusters, and phylogenetic network analysis identified four major groups. The ToxoDB PCR-RFLP #7, Type III and II were major lineages identified from Central and South America, with high frequencies of the closely related ToxoDB PCR-RFLP #7 and Type III lineages. Taken together, this study revealed high diversity within and between T. gondii populations in Central and South America, and the dominance of Type III and its closely related ToxoDB PCR-RFLP #7 lineages.


Genetic characterization of human immunodeficiency virus type 1 in blood and genital secretions: evidence for viral compartmentalization and selection during sexual transmission.
To explore the mechanism of sexual transmission of human immunodeficiency virus type 1 (HIV-1), we compared HIV-1 gp120 sequences in longitudinal samples from five acute seroconvertors with those from their corresponding sexual partners (transmitters). We used a quantitative homoduplex tracking assay to compare the overall genetic composition of HIV-1 quasispecies in each transmission pair and to track the transmitted viruses during the acute and asymptomatic stages of HIV-1 infection. In the chronically infected transmitters, HIV-1 variants in genital secretions differed from those in blood and variants in cells differed from those in cell-free plasma, indicating remarkable sequence heterogeneity in these subjects as well as compartmentalization of the virus in different bodily sites. Conversely, two of five seroconvertors had only a few related variants and three of five harbored only one viral population, indicating that in these subjects the transmitted viruses were typically homogeneous. Transmitted viruses were evident in the donor's seminal plasma (one of five cases) and even more so in their seminal cells (three of five cases), suggesting that both cell-associated and cell-free viruses can be transmitted. In every pair studied, the transmitted variant(s) represents only a minor population in the semen of the corresponding transmitter, thereby providing evidence that HIV-1 selection indeed occurs during sexual transmission.


Functional and radiological outcomes of 360 degrees fusion of three or more motion levels in the lumbar spine for degenerative disc disease.
This is a single-center, multisurgeon, retrospective study of radiologic and functional outcome measures at a minimum 2-year follow-up. We studied the radiologic and functional outcomes following 3 or more motion segment fusions of the lumbar spine for low back pain due to multilevel degenerative disc disease. Good functional outcomes have been reported for 1 or 2-level fusions, but there are no reports dealing specifically with 3 or more level fusions. A total of 80 adult patients met the inclusion/exclusion criteria of multilevel (3 or more motion segments) 360 degrees fusion for lumbar degenerative disc disease, failed nonoperative treatment for at least 1 year, no previous lumbar fusion, no fracture, tumor or infection of the spine, completed preoperative and postoperative functional questionnaires including SF-36 (n = 80), Oswestry (n = 69), Roland Morris (n = 68), and radiologic evaluation of fusion solidity with a minimum follow-up of 2 years. The average patient age was 57 years (range, 27-81). The mean follow-up was 4 years (2-7). On average, patients had fusion of 4 motion segments (range, 3-8 levels). Solid arthrodesis at the first surgery was achieved in 65/80 (81%). Adjacent segment degeneration was noted in 11 patients. Of these, 5 had undergone an extension of their fusion within the study period. There were no deaths or neurologic complications. Deep wound infection occurred in 2 patients, neither requiring implant removal. The Oswestry Disability Index scores improved from 49.8 to 35.1 (29.5%) (P < 0.001). The Roland Morris scores improved from 17.6 to 12.2 (30.7%) (P < 0.001). For the SF-36 scales, significant (P < 0.001) improvement was seen in all scales except Role Emotional scores and Mental Composite Scales. The surgical treatment of lumbar degenerative disc disease by 360 degrees fusion should be considered for properly selected patients. The goal of surgery is reduction, not elimination of disability.


Higher Circulating miR-199a-5p Indicates Poor Aerobic Exercise Capacity and Associates With Cardiovascular Dysfunction During Chronic Exposure to High Altitude.
Hypoxia-induced decline in exercise capacity is ubiquitous among lowlanders who immigrated to high altitudes, which severely reduces their work efficiency and quality of life. Although studies have revealed that hypoxia-induced cardiovascular dysfunction limits exercise capacity at high altitudes, the mechanisms have not been well explored at the molecular level. miR-199a-5p is hypoxia-sensitive and serves as an important regulator in cardiovascular pathophysiology. However, whether miR-199a-5p is involved in cardiovascular dysfunction at high altitudes and contributes to subsequent reductions in exercise capacity remains unknown. Thus, this study aimed at exploring these relationships in a high altitude population. A total of 175 lowlanders who had immigrated to an altitude of 3,800 m 2 years previously participated in the present study. The level of plasma miR-199a-5p and the concentration of serum myocardial enzymes were detected by qRT-PCR and ELISA, respectively. Indices of cardiovascular function were examined by echocardiography. The exercise capacity was evaluated by Cooper's 12-min run test and the Harvard Step Test. Furthermore, we explored the biological functions of miR-199a-5p with silico analysis and a biochemical test. The level of miR-199a-5p was significantly higher in individuals with poor exercise capacity at 3,800 m, compared with those with good exercise capacity (p < 0.001). miR-199a-5p accurately identified individuals with poor exercise capacity (AUC = 0.752, p < 0.001). The level of miR-199a-5p was positively correlated with cardiovascular dysfunction indices (all, p < 0.001). Furthermore, miR-199a-5p was involved in the oxidative stress process. In this study, we reported for the first time that the level of circulating miR-199a-5p was positively associated with exercise capacity during chronic hypoxia at high altitudes. Moreover, higher miR-199a-5p was involved in hypoxia-induced cardiovascular dysfunctions, thus contributing to poorer exercise endurance at high altitudes.


Effect of sampling site on the diagnosis of canine parvovirus infection in dogs using polymerase chain reaction.
Accurate diagnosis is imperative in dogs with clinical signs of parvovirus infection (CPV-2). To assess quantitative real-time PCR (qRT-PCR) for the diagnosis of CPV-2 infection, and determine the optimal sampling site. Secondarily, to compare qRT-PCR with a point-of-care PCR kit (PCRun), and to assess sensitivity of serology for CPV diagnosis. Sixty dogs with naturally acquired parvovirus infection, 44 unvaccinated puppies, of which 16 were followed after first and second vaccination, 15 adult dogs, of which 10 were followed also after a booster vaccine, and 9 dogs with distemper virus infection. Prospective study. Samples from the rectum, blood, and pharynx were obtained for PCR. All dogs with a clinical diagnosis of parvovirus infection were positive by qRT-PCR in at least 1 sampling site (ie, rectum, blood, pharynx), and 50 (83%) of 60 were positive in all sites. qRT-PCR was negative in 67 (99%) of 68 healthy puppies (before-vaccination), puppies with distemper, and healthy adult dogs. Ten days after initial vaccination of puppies, 62% (fecal), 31% (blood), and 12% (pharyngeal) of samples were positive for CPV-2 on qRT-PCR. The proportion of positive pharyngeal samples decreased 20 days after vaccination and all sites were negative 12-28 days after second vaccination. Vaccinated adults were negative before and after booster vaccination. Molecular detection of CPV is sensitive, but specificity is hampered temporarily during the vaccination period. Blood, feces, and pharynx are suitable sampling sites. Fecal samples had the lowest sensitivity in sick dogs and highest positivity in puppies after vaccination.


Cerebrovascular accident associated with dipyridamole thallium-201 myocardial imaging: case report.
A patient with known aortoiliac occlusive disease and hypertension suffered a cerebrovascular accident 6.5 min after the administration of intravenous dipyridamole during a 201Tl myocardial study. Despite aminophylline administration, the patient developed a completed stroke. The mechanism most likely responsible for precipitating this patient's stroke is dipyridamole-induced vascular steal. Although dipyridamole-201Tl myocardial imaging is relatively free of major complications, the morbidity and mortality associated with a cerebrovascular accident is significant. The possibility of precipitating a cerebrovascular accident during dipyridamole-201Tl imaging should be considered in all patients with significant risk factors for stroke before performing a dipyridamole cardiac study.


Pharmacological properties of shikonin - a review of literature since 2002.
The naphthoquinone shikonin is the main active principle of Zicao, a traditional Chinese herbal medicine made from the dried root of Lithospermum erythrorhizon. Studies carried out over the past 30 years have provided a scientific basis for the use of Zicao which has been long employed in folk medicine to treat a variety of inflammatory and infectious diseases. In particular, shikonin has been shown to possess many diverse properties, including antioxidant, anti-inflammatory, antithrombotic, antimicrobial, and wound healing effects. The fact that shikonin shows so many beneficial properties has increased the interest in this molecule dramatically, especially in the past few years. The aim of this review is to provide an update of the new data published on shikonin, whose wide spectrum of pharmacological effects as well as pharmacokinetic properties and toxicity make it a highly interesting target molecule.


Latent tuberculosis infections in hard-to-reach drug using population-detection, prevention and control.
Interferon-gamma release assays (IGRAs) need be evaluated for effectiveness as screening tests for tuberculosis (TB) infection in drug users. These tests have demonstrated improved sensitivity and specificity, but have not been studied in drug users. These one step blood tests are intended to replace the tuberculin skin test (TST), which is difficult to use and requires 48 hour follow-up, so they are expected to be particularly suitable for risk groups, like drug users, in whom follow-up is problematic. Drug users have traditionally been identified as being at increased risk for acquiring TB disease. The results of our pilot study using the TST and simpler and more sensitive interferon-gamma release assays showed that about 45% of current drug users in Houston tested have at least one test positive for latent tuberculosis infection (LTBI). These preliminary data suggest that there is an important reservoir of LTBI in drug using populations, and the risk of progression to active TB disease with other infections is great. However, LTBI in drug using populations has not been studied in depth and deserves further investigation. We need to evaluate the validity of IGRAs for detection of latent TB infection, the factors associated with LTBI, the incidence and risk for developing active TB disease in drug users and the effectiveness of early treatment of LTBI. We believe that using better tuberculosis screening tools will allow us to more accurately measure the prevalence of latent TB infection and incidence of active TB disease in drug using populations and develop more effective TB prevention and treatment interventions in the community.


Association between prenatal maternal cigarette smoking and early childhood caries. A systematic review.
The aim of the present study was to assess the relationship between prenatal maternal cigarette smoking (PMCS) and early childhood caries (ECC) through a systematic review of currently available scientific evidence. To address the focused question: "Is there an association between PMCS and ECC?" an electronic literature search without time or language restrictions was conducted till May 2017 in indexed databases using various key words including dental caries, pregnancy, smoking, tobacco products and child. Letters to the editor, commentaries, reviews, case reports and case series and studies in which, ECC was investigated without clinical dental examination, were excluded. Eight observational cross-sectional studies were included. The number of participants ranged between 1102 and 76920 children with age ranging between 24 months and 72 months. Seven studies reported a positive association between PMCS and ECC. One study reported that children whose mother smoked at least five cigarettes/day during pregnancy presented a higher caries severity level compared with to those whose mothers did not smoke. One study showed no association between ECC and PMCS. The association between PMCS and ECC remains debatable. Further well-designed longitudinal studies are needed in this regard. Key words:Cigarette, early childhood caries, pregnancy, risk factors, smoking.


SIRT3 Protects Against Acute Kidney Injury via AMPK/mTOR-Regulated Autophagy.
Acute kidney injury (AKI), which involves the loss of kidney function caused by damage to renal tubular cells, is an important public health concern. We previously showed that sirtuin (SIRT)3 protects the kidneys against mitochondrial damage by inhibiting the nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome, attenuating oxidative stress, and downregulating proinflammatory cytokines. In this article, we investigated the role of autophagy, mediated by a mammalian target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK), in the protective effect of SIRT3, against sepsis-induced AKI, in a mouse model of cecal ligation and puncture (CLP). The AKI in CLP mice was associated with the upregulation of autophagy markers; this effect was abolished in SIRT3- mice in parallel with the downregulation of phospho (p)-AMPK and the upregulation of p-mTOR. Pretreatment with the autophagy inhibitor 3-methyladenine (3-MA) or AMPK inhibitor compound isotonic saline (C), exacerbated AKI. SIRT3 overexpression promoted autophagy, upregulated p-AMPK and downregulated p-mTOR in CLP mice, attenuating sepsis-induced AKI, tubular cell apoptosis, and inflammatory cytokine accumulation in the kidneys. The blockage of autophagy induction largely abolished the protective effect of SIRT3 in sepsis-induced AKI. These findings indicate that SIRT3 protects against CLP-induced AKI by inducing autophagy through regulation of the AMPK/mTOR pathway.


Neurofeedback Tunes Scale-Free Dynamics in Spontaneous Brain Activity.
Brain oscillations exhibit long-range temporal correlations (LRTCs), which reflect the regularity of their fluctuations: low values representing more random (decorrelated) while high values more persistent (correlated) dynamics. LRTCs constitute supporting evidence that the brain operates near criticality, a state where neuronal activities are balanced between order and randomness. Here, healthy adults used closed-loop brain training (neurofeedback, NFB) to reduce the amplitude of alpha oscillations, producing a significant increase in spontaneous LRTCs post-training. This effect was reproduced in patients with post-traumatic stress disorder, where abnormally random dynamics were reversed by NFB, correlating with significant improvements in hyperarousal. Notably, regions manifesting abnormally low LRTCs (i.e., excessive randomness) normalized toward healthy population levels, consistent with theoretical predictions about self-organized criticality. Hence, when exposed to appropriate training, spontaneous cortical activity reveals a residual capacity for "self-tuning" its own temporal complexity, despite manifesting the abnormal dynamics seen in individuals with psychiatric disorder. Lastly, we observed an inverse-U relationship between strength of LRTC and oscillation amplitude, suggesting a breakdown of long-range dependence at high/low synchronization extremes, in line with recent computational models. Together, our findings offer a broader mechanistic framework for motivating research and clinical applications of NFB, encompassing disorders with perturbed LRTCs.


Attitudes towards family size and family planning among women at an antenatal clinic in Maiduguri, Nigeria.
"This report describes a family planning survey [involving 172 women] conducted at an antenatal clinic in Maiduguri, Nigeria between June and August 1984. The level of education of respondents is generally low and appears to have a negative effect on knowledge, approval, and use of family planning. Breast feeding is widespread but not many respondents practiced it as a method of family planning. While there is limited knowledge and some approval of family planning, a desire for large families continues and there is relatively little practice of family limitation. The prospects for a decrease in fertility in the near future is not encouraging."


Controllable 3D alginate hydrogel patterning via visible-light induced electrodeposition.
The fabrication of alginate hydrogel in 3D has recently received increasing attention owing to its distinct efficacy as biocompatible scaffold for 3D cell culture, biomedical and tissue engineering. We report a controllable 3D alginate hydrogel patterning method by developing a visible-light induced electrodeposition chip. The chip mainly consists of a photoconductive titanyl phthalocyanine (TiOPc) anode plate, an indium tin oxide (ITO) cathode plate and the mixed solution (1% sodium alginate and 0.25% CaCO3 nano particles) between them. After a designed visible-light pattern is projected onto the TiOPc plate, the produced H(+) by electrolysis will trigger Ca(2+) near the anode (illuminated area), and then the gelation of calcium alginate patterns, as desired, happens controllably. In addition, we further establish an exponential model to elucidate the gel growth v.s. time and current density. The results indicate that the proposed method is able to fabricate various 3D alginate hydrogel patterns in a well controllable manner, and maintain the laden cells at high survival rate (>98% right after gel formation). This research paves an alternative way for 3D alginate hydrogel patterning with high controllability and productivity, which would benefit the research in biomedical and tissue engineering.


The clinical evaluation of an outbreak of aseptic meningitis in children.
Aseptic meningitis is a common disease in children; The present report describes the clinical and laboratory studies of 62 children involved in an outbreak of aseptic meningitis. Sixty-two children with aseptic meningitis having been hospitalized from February to June 1993 were evaluated. The clinical data were obtained by review of the medical records. Initial cerebrospinal fluid (CSF) laboratory values were recorded, and CSF specimens were submitted to determine the viral etiology. Thirty-three percent of the cases were aged 2-5 years. Echovirus 30 was isolated from CSF specimens in 17 children, this is the only virus isolated from CSF during this period. The illness was characterized by transient fever, headache and vomiting. There was wide variation in the number of leukocyte from 14 to 2333 cell/mm3 in the spinal fluid. CSF protein ranged from 19 mg/dL to 114 mg/dL, and CSF sugar was normal in all specimens. Virus isolation was related to the cell count in CSF. There was no significant relationship between CSF cell count and protein content (r = 0.162, p = 0.2237). Hospital stay ranged from 1 to 14 days with an average of 3.9 days. CONCLUSIONS. The disease was mild and self-limiting without death or complication. Enterovirus isolation from CSF can substantially establish the diagnosis and the subsequent management, therefore, early discharge is expectable.


Is early activity resumption after paediatric concussion safe and does it reduce symptom burden at 2 weeks post injury? The Pediatric Concussion Assessment of Rest and Exertion (PedCARE) multicentre randomised clinical trial.
Investigate whether resuming physical activity (PA) at 72 hours post concussion is safe and reduces symptoms at 2 weeks, compared with resting until asymptomatic. Real-life conditions, multicentre, single-blinded randomised clinical trial, conducted in three Canadian paediatric emergency departments (ED). Children/youth aged 10-<18 years with acute concussion were recruited between March 2017 and December 2019, and randomly assigned to a 4-week stepwise return-to-PA protocol at 72 hours post concussion even if symptomatic (experimental group (EG)) or to a return-to-PA once asymptomatic protocol (control group (CG)). The primary outcome was self-reported symptoms at 2 weeks using the Health and Behaviour Inventory. Adherence was measured using accelerometers worn 24 hours/day for 14 days post injury. Adverse events (AE) (worsening of symptoms requiring unscheduled ED or primary care visit) were monitored. Multivariable intention-to-treat (ITT) and per-protocol analyses adjusting for prognostically important covariates were examined. Missing data were imputed for the ITT analysis. 456 randomised participants (EG: N=227; mean (SD) age=13.3 (2.1) years; 44.5% women; CG: N=229; mean (SD) age=13.3 (2.2) years; 43.7% women) were analysed. No AE were identified. ITT analysis showed no strong evidence of a group difference at 2 weeks (adjusted mean difference=-1.3 (95% CI:-3.6 to 1.1)). In adherent participants, initiating PA 72 hours post injury significantly reduced symptoms 2 weeks post injury, compared with rest (adjusted mean difference=-4.3 (95% CI:-8.4 to -0.2)). Symptoms at 2 weeks did not differ significantly between children/youth randomised to initiate PA 72 hours post injury versus resting until asymptomatic; however, many were non-adherent to the intervention. Among adherent participants, early PA was associated with reduced symptoms at 2 weeks. Resumption of PA is safe and may be associated with milder symptoms at 2 weeks. 1b. NCT02893969. Pediatric Concussion Assessment of Rest and Exertion (PedCARE).


Accurate harmonic phase tracking of tagged MRI using locally-uniform myocardium displacement constraint.
Harmonic phase (HARP) tracking is one of the most commonly used techniques for estimating the myocardium regional function from tagged cardiac Magnetic Resonance Imaging sequences. Nevertheless, tag fading and phase distortion can severely limit the tracking accuracy of the technique. In this work, we propose to modify the HARP tracking algorithm to impose a constraint of locally uniform displacement field while tracking the different myocardium points. A numerical contracting phantom and a dataset of 11 patients are used to study the performance of the proposed technique at the different cardiac phases, slices, and regions. The results show that the proposed method improves the tracking accuracy and the reliability of the conventional HARP technique.


Evolving paradigms in pharmacovigilance.
All medicines have adverse effects as well as benefits. The aim of pharmacovigilance is to protect public health by monitoring medicines to identify and evaluate issues and ensure that the overall benefits outweigh the potential risks. The tools and processes used in pharmacovigilance are continually evolving. Increasingly sophisticated tools are being designed to evaluate safety data from clinical trials to enhance the likelihood of detecting safety signals ahead of product registration. Methods include integration of safety data throughout development, meta-analytical techniques, quantitative and qualitative methods for evaluation of adverse event data and graphical tools to explore laboratory and biometric data. Electronic data capture facilitates monitoring of ongoing studies so that it is possible to promptly identify potential issues and manage patient safety. In addition, GSK employs a number of proactive methods for post-marketing signal detection and knowledge management using state-of-the-art statistical and analytical tools. Using these tools, together with safety data collected through pharmacoepidemiologic studies, literature and spontaneous reporting, potential adverse drug reactions can be better identified in marketed products. In summary, the information outlined in this paper provides a valuable benchmark for risk management and pharmacovigilance in pharmaceutical development.


Comparison of Nitroglycerin and Terbutaline for External Cephalic Version in Women Who Received Neuraxial Anesthesia: A Retrospective Analysis.
External cephalic version is a technique that decreases the need for cesarean delivery in patients with breech presentation. Several techniques exist to increase the success of external cephalic version; however, there are no studies comparing different tocolytics in patients who also received neuraxial anesthesia. We, therefore, performed a review of 198 patients who presented for external cephalic version and compared their success rates based on the tocolytic medication utilized. The external cephalic version success rate for patients who received terbutaline was significantly higher than for those who received nitroglycerin (N [%]: 57 [65.6] terbutaline group versus 40 [36.0] nitroglycerin group; P < .001).


Echocardiographic follow-up of patients with Takayasu's arteritis: five-year survival.
Takayasu's arteritis (TA) is a primary vasculitis that causes stenosis or occlusion, rarely aneurysm and distal ischemia. This study was undertaken to examine cardiovascular damage using echocardiography and determine the causes of morbid-mortality in Mexican Mestizo patients with TA. Seventy-six patients were studied by transthoracic echocardiography. Left ventricular diameters, parietal thickness, systolic function, and wall motion were analyzed, also, valvular lesions and aorta features were assessed. Thickness of the interventricular septum was 12 mm +/- 3 (8-19), and that of posterior wall was 12 mm +/- 2 (9-18). The average left ventricular diastolic diameter was 47 mm +/- 7 (33-68) and the left ventricular systolic diameter 32 mm +/- 8 (16-64). The left ventricular ejection fraction was of 57 +/- 11%. Left ventricular concentric hypertrophy was found in 28 (50%) of the 56 hypertensive patients. The five-year survival of patients with left ventricular concentric hypertrophy was 80%, compared to 95% in patients without hypertrophy (P = 0.00). Abnormal wall motion was found in 15 patients. Thirty-one patients had aortic regurgitation, 19 had mitral regurgitation, 13 had tricuspid regurgitation, and 10 and pulmonary hypertension. Six patients had aneurysms of ascending aorta and 7 stenosis of descending aorta. Thirteen of 76 patients died (17%), 85% were hypertensive, and 9% also had acute myocardial infarction (AMI). Echocardiography, a noninvasive technique, shows a great utility in detection and follow-up of cardiovascular manifestations in patients with TA. New techniques, more sensitive toward detecting the early stages of left ventricular dysfunction, are promising to limit left ventricular hypertrophy development.


Tightly controlled WRKY23 expression mediates Arabidopsis embryo development.
The development of a multicellular embryo from a single zygote is a complex and highly organized process that is far from understood. In higher plants, apical-basal patterning mechanisms are crucial to correctly specify root and shoot stem cell niches that will sustain and drive post-embryonic plant growth and development. The auxin-responsive AtWRKY23 transcription factor is expressed from early embryogenesis onwards and the timing and localization of its expression overlaps with the root stem cell niche. Knocking down WRKY23 transcript levels or expression of a dominant-negative WRKY23 version via a translational fusion with the SRDX repressor domain affected both apical-basal axis formation as well as installation of the root stem cell niche. WRKY23 expression is affected by two well-known root stem cell specification mechanisms, that is, SHORTROOT and MONOPTEROS-BODENLOS signalling and can partially rescue the root-forming inability of mp embryos. On the basis of these results, we postulate that a tightly controlled WRKY23 expression is involved in the regulation of both auxin-dependent and auxin-independent signalling pathways towards stem cell specification.