Clinical and Radiographic Comparison of Oblique Lateral Lumbar Interbody Fusion and Minimally Invasive Transforaminal Lumbar Interbody Fusion in Patients with L4/5 grade-1 Degenerative Spondylolisthesis.
To compare the clinical and radiographic outcomes of oblique lateral lumbar interbody fusion and minimally invasive transforaminal lumbar interbody fusion in patients with grade-1 L4/5 degenerative spondylolisthesis. Based on the inclusion and exclusion criteria, the comparative analysis included consecutive patients with grade-1 degenerative spondylolisthesis who underwent oblique LIF (OLIF, n = 36) or minimally invasive transforaminal LIF (MI-TLIF, n = 45) at the Department of Spine Surgery, Beijing Jishuitan Hospital from January 2016 to August 2017. Patient satisfaction Japanese Orthopaedic Association score, visual analog scale (VAS) scores for back and leg pain, Oswestry disability index (ODI), radiographic outcomes including anterior/posterior disc heights (ADH/PDH), foraminal height (FH), foraminal width (FW), cage subsidence, cage retropulsion, and fusion rate were assessed during a 2-year follow-up. Continuous data are presented as mean ± standard deviation and were compared between groups using the independent sample t-test. Categorical data are presented as n (%) and were compared between groups using the Pearson chi-squared test or Fisher's exact test. Repetitive measurement and analysis of variance was employed in the analysis of ODI, back pain VAS score, and leg pain VAS score. Statistical significance was defined as p < 0.05. The OLIF and MI-TLIF groups comprised 36 patients (age, 52.1 ± 7.2 years; 27 women) and 45 patients (age, 48.4 ± 14.4 years; 24 women), respectively. Satisfaction rates at 2 years post procedure exceeded 90% in both groups. The OLIF group had less intraoperative blood loss (140 ± 36 vs 233 ± 62 mL), lower back pain VAS score (2.42 ± 0.81 vs 3.38 ± 0.47), and ODI score (20.47 ± 2.53 vs 27.31 ± 3.71) at 3 months follow-up (with trends toward lower values at 2 years follow-up), but higher leg pain VAS scores at all postoperative time points than the MI-TLIF group (all p < 0.001). ADH, PDH, FD, and FW improved in both groups post-surgery. At the 2 year follow-up, the OLIF group had a higher rate of Bridwell grade-I fusion (100% vs 88.9%, p = 0.046) and lower incidences of cage subsidence (8.33% vs 46.67%, p < 0.001) and retropulsion (0% vs 6.67%, p = 0.046) than the MI-TLIF group. In patients with grade-I spondylolisthesis, OLIF was associated with lower blood loss and greater improvements in VAS for back pain and ODI and radiologic outcomes than MI-TLIF. The OLIF is more suitable for these patients with low back pain as the main symptoms are accompanied by mild or no leg symptoms before operation.


Evaluating Liver Biopsies with Well-Differentiated Hepatocellular Lesions.
Needle core biopsies of liver lesions can be challenging, particularly in cases with limited material. The differential diagnosis for well-differentiated hepatocellular lesions includes focal nodular hyperplasia, hepatocellular adenoma, and well-differentiated hepatocellular carcinoma (HCC) in noncirrhotic liver, while dysplastic nodules and well-differentiated HCC are the primary considerations in cirrhotic liver. The first part of this review focuses on histochemical and immunohistochemical stains as well as molecular assays that are useful in the differential diagnosis. The second portion describes the features of hepatocellular adenoma subtypes and focuses on the differential diagnoses in commonly encountered clinicopathologic scenarios.


A study of exercise performance and heart rate: the response to exercise of a small group of manual workers before and after retirement.
Measurements of walking pattern, exercise performance, heart rate response to exercise and body composition have been made in 13 male manual workers at retirement and again one and two years later. The exercise consisted of walking, in accordance with standard instructions; heart rate and footfall signals were recorded on magnetic tape during the test using body-borne tape recorders. After the first year highly significant reductions in walking speed were found but no significant changes in walking pattern, heart rate response or body composition. When the measurements made at the end of one year of retirement were compared with those made at the end of two years no significant changes were found.


[Acute post-traumatic renal insufficiency with chronic pyelonephritis].
The course of acute renal failure induced by an injury of the chronically pyelonephritic kidney, the tests ensuring the diagnosis of subcapsular haematoma and the surgical correction of the lesion until its recovery, are described.


A lentiviral vector with novel multiple cloning sites: stable transgene expression in vitro and in vivo.
Gene delivery has become an important tool for biological research and gene therapy trials. Lentiviral vector (LV) mediated gene transfer is a preferred approach for stable, sustained transgenic expression. We report here step-wise development of an Indian human immunodeficiency virus type 2 (HIV-2) isolate derived third generation lentiviral vector with a novel, versatile multiple cloning site (MCS) that can also facilitate single step sub-cloning of a PCR amplified transgene cassette by T/A cloning strategy apart from useful cohesive/blunt end cloning. Efficiency of the vector systems was functionally demonstrated by development of a transgenic enhanced green fluorescence protein (GFP) expressing cell line. Further, a GFP down regulated cell line was derived from the said cell line through LV mediated shRNA expression by cloning the GFP-shRNA cassette using the T/A cloning strategy. Subsequently long term expression of GFP transgene in nude mouse spleen/liver was also documented till 30 days. This LV platform with the enhanced user friendly cloning options will be an important advancement in gene transfer technology.


Tryptophan metabolism in Japanese and British women and its relationship to endogenous steroid levels.
The excretion of the tryptophan metabolites L-kynurenine, 3-hydroxykynurenine, 3-hydroxyanthranilic acid and xanthurenic acid, by normal Japanese and British pre-menopausal, menopausal and post-menopausal women was measured after a loading dose of L-tryptophan. No significant difference was found between the mean excretion levels of the two races. A correlation with the level of plasma oestradiol and the excretion of L-kynurenine and also with the total of the four metabolites was found in pre-menopausal British women but not in Japanese women.


Double directional adjusting estrogenic effect of naringin from Rhizoma drynariae (Gusuibu).
Chinese traditional medicine Rhizoma drynariae (Gusuibu) is widely used for clinically treating osteoporosis and bone non-union. Naringin and its active metabolite naringenin are the main active ingredients of Rhizoma drynariae total flavonoids. The purpose of this paper is to confirm estrogenic and anti-estrogenic activity of naringin and naringenin, and provide the basic data to further study for the dose-effect relationship and the mechanism for Rhizoma drynariae in treatment of osteoporosis and other estrogen deficiency-related diseases. Naringin was extracted from Rhizoma drynariae. Naringin and its metabolin naringenin were tested estrogenic and anti-estrogenic activities through the experiment of cell proliferation and uterus weight gain in mice. Their estrogen-receptor binding abilities were tested by yeast two-hybrid experiment and nuclear receptor cofactor assays (RCAS) experiment, and their possible binding sites for ERβ were performed by computer aided molecular docking technology. Naringin and naringenin showed significant effects on the proliferation of estrogen-sensitive ER(+) MCF-7 cells in the absence of estrogen. Induction increased proliferation as the drug concentration, and the strongest proliferation appeared at a concentration of 8.6×10(-5)M. When estradiol (10(-10)M) and the different concentrations of naringin or naringenin were treated at the same time, naringin and naringenin could result in antagonistic effects on estradiol-induced MCF-7 cell proliferation, but they did not significantly affect proliferation of estrogen-insensitive ER(-) MDA-MB-231 cells. Naringin and naringenin exhibited higher binding capacity to estrogen receptor β (ERβ) than estrogen receptor α (ERα) in yeast two-hybrid experiments and nuclear receptor cofactor assays (RCAS) experiment. Docking simulation between naringin/naringenin and ERβ were performed, and the corresponding binding free energies of naringin-receptor and naringenin-receptor docked complexes were -7.95 and -10.45kcal/mol. Hydrogen bonds were found between naringin and the amino acid residues Lys304 and His308. The oxygen atom (O11) of naringenin formed hydrogen bond to Arg346, and there may be hydrophobic space interactions between phenyl group (C13-C18) of naringenin and the amino acid residues Leu298, Met336, Met340, Phe356, Ile376 and Leu380. Naringin and naringenin revealed a double directional adjusting function of estrogenic and anti-estrogenic activities. Both of them showed estrogenic agonist activity at low concentration or lack of endogenous estrogen. On the other hand, they also acted as estrogenic antagonists at high concentrations or too much endogenous estrogen. They produced estrogenic and anti-estrogenic effects primarily through selectively binding with ERβ, which could prevent and treat osteoporosis with the mechanism of estrogenic receptor agitation. This paper confirmed the estrogenic and anti-estrogenic activity of naringin and naringenin, and further studies were still essential to study their dose-effect relationship and the anti-osteoporosis mechanism for Rhizoma drynariae in the treatment of osteoporosis and other estrogen deficiency-related diseases.


Novel diamide-based inhibitors of IMPDH.
A series of novel amide-based small molecule inhibitors of inosine monophosphate dehydrogenase is described. The synthesis and the structure-activity relationships (SARs) derived from in vitro studies are presented.


Re-entrant ventricular arrhythmias in the late myocardial infarction period. 3. Manifest and concealed extrasystolic grouping.
Re-entrant beats with regular extrasystolic grouping were seen in 44- of dogs 3--7 days following ligation of the anterior descending coronary artery. Utilizing direct recording of the re-entrant pathway (RP) from the epicardial surface of the infarction zone, we found extrasystolic grouping to be based on the infarction tachycardia-dependent conduction disorders in a potentially RP. Trigeminy and quadrigeminy were related, respectively, to a 3:2 and 4:3 Wenckebach-like conduction cycle in a RP. However, quadrigeminy could also be due to an underlying bigeminal rhythm with concealment of alternate re-entrant beats, i.e., concealed bigeminy. A bigeminal rhythm was the result of a 2:1 conduction pattern in a re-entrant pathway with a sufficient degree of conduction delay during the conducted beat of the 2:1 cycle to result in re-entry. A trigeminal or quadrigeminal rhythm could change to a bigeminal rhythm on critical shortening of the cardiac cycle. Fixed and variable coupling were related, respectively, to stable and changing conduction pattern in a re-entrant pathway. On the other hand, extrasystolic grouping could be concealed due to either block in the re-entrant pathway or entrapment in a small area of the closely bordering normal zone.


Immunometabolism and natural killer cell responses.
Natural killer (NK) cells are lymphocytes with important roles in innate and adaptive immune responses to tumours and viral infection. However, in certain chronic diseases, including obesity and cancer, NK cell functional responses are impaired. Recently, research has highlighted the importance of NK cell metabolism in facilitating robust NK cell effector functions. This Review describes our current understanding of mouse and human NK cell metabolism and the key signalling pathways that mediate metabolic responses in NK cells. Furthermore, it explores how defects in metabolism can contribute to the generation of dysfunctional NK cells in chronic disease. Finally, the potential for new therapeutic strategies targeting cellular metabolism is discussed.


IPPP-CLOPPA Analysis of the Influence of the Methylation on the Potential Energy and the Molecular Polarizability of the Hydrogen Bonds in the Cytosine-Guanine Base Pair.
The IPPP-CLOPPA method is applied to investigate the influence of a methyl group on the energy of the hydrogen bonds and the potential energy curve of the bridge protons in model compounds, which mimic the methylated and unmethylated cytosine-guanine base pairs. On the same grounds, this influence on the polarizability of the intermolecular hydrogen bonds of these compounds is also addressed, in order to determine whether this linear response property provides a significant proof of the electronic mechanisms that affect the stabilization of the hydrogen bonds. Results obtained show that the methyl electronic system delocalizes on the hydrogen bond region, and changes of these intermolecular hydrogen bonds are due to this effect of delocalization.


The Gut Microbial Metabolite Trimethylamine N-Oxide is Linked to Specific Complications of Systemic Sclerosis.
Systemic sclerosis (SSc) is a rare immune-mediated connective tissue disease characterized by fibrosis of the skin and internal organs, whose pathogenesis is not fully understood. Recent studies have revealed dysbiosis in patients with systemic sclerosis and have indicated the possible role of the microbiota and its metabolites in the pathogenesis of the disease. Trimethylamine N-oxide (TMAO) is a compound produced by dysbiotic microbiota observed at higher concentrations in several autoimmune diseases. To determine concentrations of the bacteria-derived metabolite TMAO in patients with systemic sclerosis and to assess possible correlation between TMAO and a specific manifestation of the disease. The study included 63 patients with SSc and 47 matched control subjects. The concentration of TMAO was measured with high-performance liquid chromatography. Plasma TMAO level was significantly increased in patients with SSc (283.0 [188.5-367.5] ng/mL versus 205.5 [101.0-318.0] ng/mL; p < 0.01). An increased concentration of TMAO was observed in patients with concomitant interstitial lung disease (ILD) (302.0 ng/mL [212.0-385.5] ng/mL versus 204.0 [135.5-292.0] ng/mL; p < 0.01) and esophageal dysmotility (289.75 [213.75-387.5] ng/mL versus 209.5 ng/mL [141.5-315.0] ng/mL; p < 0.05) compared to patients without these complications. Furthermore, TMAO concentration exhibited significant correlation with markers of heart involvement (left ventricle ejection fraction, NT-proBNP), marker of ILD severity and Scleroderma Clinical Trials Consortium Damage Index. The concentration of TMAO, gut microbiota-associated metabolite, is increased in systemic sclerosis, particularly in patients with advanced organ involvement. This is the first study evaluating plasma TMAO in systemic sclerosis. Bacterial metabolites may be a link between dysbiosis and organ involvement in the course of the disease. Modulation of gut bacterial-derived metabolites may represent a new therapeutic approach in the management of systemic sclerosis.


Cytoplasmically inherited mutations of a human cell line resulting in deficient mitochondrial protein synthesis.
A large number of mutants deficient in mitochondrial protein synthesis (mtPS-) have been isolated from the human cell line VA2-B by subjecting cells partially depleted of their mtDNA to mutagenic treatments thought to be specific for mtDNA. Each of these mtPS- mutants has less than 10% of the wild-type rate of mitochondrial protein synthesis, exhibits reduced cytochrome oxidase and rutamycin sensitive ATPase activities, requires high concentrations of glucose, and grows indefinitely in the presence of 100 micrograms/ml of chloramphenicol (CAP). Fusion of cytoplasts from seven mtPS- mutants to the nucleated thioguanine-resistant VA2-B derivative TG-6 has yielded numerous cybrid clones which grow in CAP plus thioguanine, whereas almost no clones have resulted from the fusion of nucleated mtPS- cells to TG-6 cells: these results suggest that the gene(s) coding for the phenotype of mtPS- cells is localized in the cytoplasm (mtDNA?).


Socially marketed insecticide-treated nets improve malaria and anaemia in pregnancy in southern Tanzania.
To study the uptake of socially marketed insecticide-treated nets (ITNs) and their impact on malaria and anaemia in pregnancy; and to report on a discount voucher system which aimed to increase coverage in pregnancy. A 12-month cross-sectional study of women in the second or third trimester of pregnancy. ITN use and other factors were assessed by questionnaire and a blood sample taken for malaria parasitaemia and anaemia. 'Non-users' of ITNs included both women not using any net and women using untreated nets. Fifty three per cent of pregnant women used ITNs. Women aged 15-19, primigravidae, unmarried women, and those with no access to cash had the lowest ITN use. Fewer ITN users were positive for malaria than ITN non-users (25 vs. 33%: P=0.06), and the protective efficacy (PE) for parasitaemia was 23% (CI 2-41). Multiparous ITN users had a twofold decrease in parasite density compared with multiparous non-ITN users (625 parasites/microl vs. 1173 parasited/microl: P=0.01). Fewer ITN users were anaemic (Hb < 11 g/dl) than ITN non-users (72 vs. 82%: P=0.01). ITNs had a PE of 12% (CI 2-21) against mild anaemia and a PE of 38% (CI 4-60) against severe anaemia (Hb < 8 g/dl). There was a trend in the prevalence of severe, mild and no anaemia, and of high density, low density and no malaria infection by ITN status. Recently treated nets were most effective at preventing malaria and anaemia (prevalence of mild anaemia was 68% compared with 82% for those without nets (P=0.002); prevalence of malaria was 22% compared with 33% for those without nets (P=0.02). Knowledge and reported use of the discount voucher system were low. Further qualitative research is ongoing. A modest impact of ITNs on pregnancy malaria and anaemia was shown in our high malaria transmission setting. The development of ITN programmes for malaria control should include pregnant women as a specific target group.


Structure-function relationships of Ca spark activity in normal and failing cardiac myocytes as revealed by flash photography.
We describe the two-dimensional imaging of excitation-induced Ca gradients in isolated myocytes under physiological conditions, using a novel method of flash photography of fluo-3 fluorescence. This method is useful for showing the spatial distribution and reproducibility of rapidly triggered Ca release events, and their relationship to underlying structures. In normal rat myocytes, Ca sparks were evident 6ms after stimulation emerging from around t-tubules, as judged by co-localization with di-8-ANEPPS staining. Gaps in the spark pattern coincided with gaps in di-8-ANEPPS staining. Vacuolar fluo-3 uptake, previously identified as lysosomal, was prominent in some of the gaps, suggesting possible areas of t-tubule turnover. In normal dog myocytes, the beat-to-beat variance of Ca sparks was very low, t-tubular voids were small, and Ca gradients resolved rapidly. In myocytes from dogs with failure induced by rapid pacing, a reduced Ca transient was observed associated with increased areas that were void of sparks and t-tubules, and a greater beat-to-beat spark variance. These abnormalities resulted in a non-uniform spatial distribution of sparks, leading to Ca gradients across the cell that persisted for longer times after stimulation. Such Ca gradients could cause heterogeneous contraction and contribute to contractile failure.


Aspects of influx and efflux of homovanillic acid of rat cerebrospinal fluid.
In rats, different methods of perfusion (lumbar-cisternal or ventricular-cisternal) with artificial cerebrospinal fluid were performed at velocities of about 30 and 180 microliter/min. Levels of homovanillic acid (HVA) in the outflow were assayed with a semiautomated fluorimetric technique. Intravenous administration of 20 microgram HVA did not substantially enhance the outflow of this acid, indicating that in our preparations HVA found in the perfusate is of central origin. In the lumbar-cisternal preparation probenecid (200 mg/kg, i.p.) was found to inhibit the efflux of a significant fraction of HVA added to the medium, at both perfusion rates. The proportions of HVA eliminated by a probenecid sensitive transport was much higher at the lower rate of perfusion. Following probenecid the increase of endogenous HVA in the ventricular-cisternal perfusate was higher at a lower rate of perfusion. We determined the turnover rate of HVA in the whole brain and compared this value with the HVA outflow in the various preparations. The highest efflux of HVA was found in the ventricular-cisternal preparation during probenecid treatment and did not appear to be dependent upon the rate of perfusion. A maximal value of 3.5% of HVA formed in the central nervous system was found to be released into the cerebrospinal fluid.


Estimated versus actual; The accuracy of accounting for blood loss during endoscopic sinus surgery.
Endoscopic sinus surgery (ESS) is the mainstay for chronic inflammatory and neoplastic sinonasal process and as a result many modalities have been studied to minimize blood loss and patient morbidity and to maximize intraoperative visualization. However, often conclusions of actual blood loss are based on surgeons' estimations without ever actually assessing the accuracy of these estimations. The objective of this study was to determine the accuracy of intraoperative blood loss estimates by attending otolaryngology surgeons among patients undergoing ESS. After obtaining institutional review board approval, data were collected on six surgeons performing ESS at a military academic medical center for 21 surgical cases. Specifically, both hourly and end-of-case total "estimated" (EBL) and "calculated actual" (ABL) blood loss values were recorded and compared statistically. Surgeons were blinded to the results until after all data were collected. The difference between mean EBL and ABL was 62.5 ml and was statistically significant (p = .007, Power 86.2%). EBL lagged ABL for both hourly intervals during a surgical case and the total end-of-surgery values. The surgeons studied had EBL that were statistically significantly less than ABL both at hourly intervals during the surgery and at the conclusion of the case. As a result there exists potential for adverse consequences in clinical care and in efforts in medical research/advancement.


Estimation of aerobic fitness from 20-m multistage shuttle run test performance.
Aerobic fitness (VO(2)max) is a key component of youth fitness testing. Criterion-referenced (CR) assessments are used in FITNESSGRAM(®) to assess health risk. The purpose of this study was to develop and cross-validate regression models to estimate VO(2)max from Progressive Aerobic Cardiovascular Endurance Run (PACER) 20-m shuttle run performance in boys and girls aged 10-16 years. Several previously published PACER models were also cross-validated. A secondary purpose was to examine the CR validity of the models. PACER performance and VO(2)max were assessed in a sample of 244 participants. The sample was randomly split into validation (n=174) and cross-validation (n=70) samples. The validation sample was used to develop the regression models to estimate VO(2)max from PACER, BMI, gender, and age. CR validity was evaluated by comparing classification of the prediction models with classification by the criterion of measured VO(2)max. For the Quadratic Model, the multiple correlation between measured and estimated VO(2)max was 0.75, and the SE of estimate (SEE) was 6.17 mL/kg/min. Similar accuracy was found for Linear Model 2 (R=0.74; SEE=6.29 mL/kg/min). Accuracy of these models was confirmed on the cross-validation and total samples. Cross-validation demonstrated that the Quadratic Model and Linear Model 2 were slightly more accurate than previous PACER models. Evidence of CR validity for the newly developed models was of moderate levels. The Quadratic Model and Linear Model 2 provide valid estimates of VO(2)max and compare favorably to previous models. The CR validity evidence for the Quadratic Model and Linear Models developed in this study was slightly better than for the other models examined.


Fairly rare small-diameter hepatocellular carcinoma with right adrenal gland metastasis having an inferior vena cava tumor thrombus: a case report.
Hepatocellular carcinoma (HCC) may lead to extrahepatic metastasis (EHM). Most patients with EHM had either intrahepatic stage III or IVA tumor at the site of metastases. Herein, we present the case of a fairly rare 1.5-cm small-diameter HCC with right adrenal gland tumor having an inferior vena cava (IVC) tumor thrombus. A 75-year-old man had a 1.5-cm hepatocellular carcinoma (HCC) in segment 8 of the liver and a 3.0-cm right adrenal gland tumor with inferior vena cava (IVC) tumor thrombus. He underwent partial hepatectomy, right adrenalectomy, and IVC tumor thrombectomy. Tumor resection was successful, but the tumor progressed rapidly, and the patient died 8 months after the operation. Immunohistochemical staining revealed that both HCC cells and adrenal tumor cells were positive for HCC markers Glypican-3 and alpha-fetoprotein. In terms of adrenal carcinoma markers vimentin and Melan-A, vimentin was negative in the HCC and adrenal tumor, and Melan-A was negative in the HCC. In adrenal tumor, slight positivity of Melan-A was observed, but the intensity of staining was clearly weak compared with that in normal adrenal glands. CD133, one of the stem cell markers, was positive in both HCC and adrenal tumor cells. Next-generation amplicon sequencing analyses were performed using DNA derived from the HCC, adrenal tumor, and normal liver tissue. After exome data analyses for representative HCC-related genes as TERT, CTNNB1, TP53, and ARID2, TP53 mutation (exon3: c.G351 T: p.R117S) was found in both HCC cells and adrenal tumor cells. Conversely, no significant mutations in other genes were observed. These pathological findings and sequencing results showed that the adrenal tumor might be an adrenal metastasis of HCC in spite of small primary tumor size. This case suggests that the right adrenal tumor was a metastasis of HCC. Immunohistochemical staining and gene mutation analyses using NGS are very useful in differentiating the tumor origin.


Cholesterol ester storage disease: clinical, biochemical, and pathological studies of four new cases.
Cholesterol ester storage disease (CESD) is infrequent in children. Four new cases in two nonrelated families are presented. Acid lipase deficiency in the leukocytes of the patients and reduced activity (50%) in those of parents were demonstrated. Clinical manifestations varied from neonatal cholestasis to asymptomatic hepatomegaly. Hepatic histology showed lipid vacuoles and cholesterol ester storage in hepatocytes and Kupffer cells. Increased levels of cholesterol and hepatomegaly were the first findings. There is as yet no specific treatment for CESD; however, the early detection of cases would make possible the timely control of complications.


Our experience on the management of acute mastoiditis in pediatric acute otitis media patients.
The incidence of complications due to acute otitis media (AOM) in childhood has decreased significantly with the use of new antibiotics in recent years. However, acute mastoiditis (AM) is still the most common complication that can lead to further intracranial conditions with high morbidity. Our study aimed to evaluate the clinical characteristics of children with AM and identify possible indicators for further intracranial complications associated with this condition. Children hospitalized in our clinic with a diagnosis of AM were reviewed. Demographic data, disease-related symptoms, types of complications accompanied by AM, medical/surgical treatments modalities, and culture results were screened. The patients were divided into two groups as those with and without intracranial complications (ICCs). Routine complete blood count tests, biochemical analysis, and C-reactive protein (CRP) level measurement were evaluated and compared between the groups. Of the 28 AM patients, five (17.9%) had isolated AM. Complications associated with AM included sub-periosteal abscess (28.6%), facial paralysis (25%), meningitis (17.9%), meningitis with sigmoid sinus thrombosis (7.1%), and meningitis with cerebellar abscess (3.6%). Eight patients developed ICCs (28.6%), of whom three had more than one complication. Ceftriaxone was found to be the first-line medical treatment (57.1%). Streptococcus pneumoniae was the most common pathogen isolated from the cultures (42.9%). Three patients (10.7%) were treated non-surgically, eight (28.6%) with myringotomy and ventilation tube (VT) insertion, eight patients (28.6%) with abscess drainage and VT insertion, and nine (32.1%) with cortical mastoidectomy and VT insertion. There was no significant difference between the patients with and without ICCs in terms of complete blood count parameters. The CRP level and the CRP-albumin ratio were significantly higher in patients with ICCs than those without these complications (p < 0.001). AM remains to be the most common complication of AOM in childhood and can lead to further life-threatening conditions. Additional interventions according to the type of the complication with VT insertion is safe and effective in the management of AM. In patients with AM, it is of great importance to determine whether there is an accompanying ICC. The CRP-albumin ratio is a simple and reliable calculation to detect ICCs in patients with AM.


Suicidal deaths in pregnancy at an apex institute in India: A retrospective analysis of autopsy cases.
Suicidal behavior in pregnancy is a known fact worldwide. However, the published literature is still debating whether pregnancy is associated with an increase in the risk of suicide. Nonetheless, this is an important phenomenon that should not be ignored as the life of an unborn fetus is involved. The present study is a retrospective analysis of suicide death in pregnancy for the years 2011-2020 to study the different parameters. The cases were collected from the archives of the department with due permission from the authority. Data were analyzed according to the age of the victim, duration of pregnancy, and time and cause of death. The commonest age group was 21-25 years, the time of death was mostly during the daytime, and most of the deaths were due to hanging. These findings are not unusual in comparison to the general population. The pregnancy duration of most of the cases was first and second trimester, and third-trimester pregnancy accounted for far less number. In contrast, some studies showed that suicidal ideation and depression were more common during the first trimester and third trimester. Most of the pregnant women were pregnant with male fetuses. Though suicidal ideation is more during the first and third trimester, suicide occurs mostly in the first and second trimester, with third-trimester suicide deaths being far less. Being pregnant with a male fetus might be a risk factor in comparison to having female fetuses. These are two aspects that need to be explored further.


Women's intentions to use fertility preservation to prevent age-related fertility decline.
The optimal age to cryopreserve oocytes for later use is before 36 years. Current users are on average 38 years old. In this cross-sectional study an online survey was constructed about the factors associated with the intentions of childless women aged 28-35 years to use fertility preservation (FP). Questions were derived from the Theory of Planned Behaviour (attitudes and subjective norms regarding FP and perceived behaviour control to do FP) and the Health Belief Model (perceived susceptibility of infertility, perceived severity of childlessness, barriers and benefits of FP and cue to use FP). Also addressed were parenthood goals, fertility knowledge and intentions to use FP within 2 years. The data were analysed using structural equation modelling. The Health Belief Model showed a good fit to the data (χ(2) [14, n = 257] = 13.63, P = 0.477; CFI = 1.000: RMSEA = 00, 90% CI [0.00-0.06]). Higher intentions to use FP were associated with feeling susceptible to infertility, considering FP useful to achieve parenthood, perceiving the implications of infertility as severe, expecting to have children at a later age and having fewer ethical concerns. This suggests an increase of fertility awareness is necessary for the optimal use of FP.


Elevated placental expression at the maternal-fetal interface but diminished maternal circulatory kisspeptin in preeclamptic pregnancies.
To investigate the placental mRNA and protein expression of metastasis suppressor gene Kiss-1 and the transcript expression of its receptor GPR-54 across the maternal-fetal interface of healthy and preeclamptic pregnancies. To furthermore compare placental tissue kisspeptin expression to circulatory kisspeptin levels in these pregnancies. Secondary and Tertiary Hospital Setting in Cape Town, South Africa. Patients with and without preeclampsia undergoing elective caesarean delivery. The placenta, placental bed and decidua parietalis as well as maternal and cord blood in both healthy and preeclamptic pregnancies were simultaneously sampled at elective caesarean delivery. RT-PCR was utilised to determine mRNA expression while immunohistochemistry was employed to investigate protein expression in maternal-fetal tissues. Circulating maternal and cord serum kisspeptin concentrations were determined using ELISA. Maternal-fetal tissue mRNA expression of Kiss-1 and GPR-54 as well as maternal/cord serum kisspeptin concentrations in healthy and preeclamptic pregnancies. There was high placental kisspeptin expression but low circulating serum kisspeptin levels in pregnancies complicated by preeclampsia. Kiss-1 mRNA and protein expression was minimal in the maternal tissues (placental bed and decidua parietalis) of both healthy and preeclamptic pregnancies. No difference was found in Kiss-1 receptor (GPR-54) mRNA expression across maternal-fetal tissues of healthy and preeclamptic pregnancies. Increased placental kisspeptin expression is consistent with reduced trophoblast invasiveness and may represent a molecular mechanism that explains the development of preeclampsia. Decreased circulating kisspeptin concentration has the potential to be utilised as a marker for placental dysfunction.


Validation of the Communication Profile-Adapted in Ethiopian children with neurodevelopmental disorders.
Neurodevelopmental disorders (NDDs) are conditions affecting a child's cognitive, behavioural, and emotional development. Appropriate and validated outcome measures for use in children with NDDs in sub-Saharan Africa are scarce. The aim of this study was to validate the Communication Profile Adapted (CP-A), a measure developed in East Africa to assess caregivers' perception of communication among children with NDDs. We adapted the CP-A for use in Ethiopia, focusing on the communicative mode (CP-A-mode) and function (CP-A-function) scales. The CP-A was administered to a representative sample of caregivers of children with NDDs and clinical controls. We performed an exploratory factor analysis and determined the internal consistency, test-retest reliability, within-scale, known-group, and convergent validity of the identified factors. Our analysis included N = 300 participants (N = 139 cases, N = 139 clinical controls, N = 22 who did not meet criteria for either cases or controls). Within the CP-A-mode, we identified two factors (i.e. verbal and physical communication); the CP-A-function scale was unidimensional. Combining both scales into one summary variable (the CP-A-total) resulted in a scale with excellent internal consistency and test-retest reliability (Cronbach's alpha = 0.97; Kappa = 0.60-0.95, p < 0.001; ICC = 0.97, p < 0.001). Testing known-group validity, the CP-A-total scores were significantly higher for controls than cases (Δ mean = 33.93, p < 0.001). Convergent validity assessment indicated that scores were negatively and moderately correlated with clinical severity (ρ = -0.25, p = 0.04). The CP-A is a valid tool for the assessment of communication among children with NDDs in Ethiopia. It holds promise as a brief, quantitative, and culturally appropriate outcome measure for use in sub-Saharan Africa.


Transcatheter recanalization and subsequent stent implantation for the treatment of early postoperative thrombosis of modified Blalock-Taussig shunts in two children.
Two babies with duct-dependent cyanotic congenital heart disease were palliated with modified Blalock-Taussig shunts. One patient was diagnosed to have tetralogy of Fallot, and the other patient, tricuspid atresia type Ia. Early postoperative arterial oxygen saturations dropped significantly due to shunt thrombosis. Both patients were successfully treated with angioplasty and stent implantation.


Do ferns and lycophytes function as medicinal plants? A study of their low representation in traditional pharmacopoeias.
Ethnobotany is becoming an important tool for understanding how traditional medical systems are organized and which variables affect their structure and dynamics. However, some phenomena observed in ethnobotanical studies led us to question whether such phenomena are real or methodological artifacts. The small proportion of ferns and lycophytes in ethnobotanical surveys of medicinal plants is one such phenomenon, and its causes should be identified using different approach levels. The present study aimed to clarify the reasons for a low representation of these two groups in studies of medicinal plants. The present study considered the following hypotheses: 1) ferns and lycophytes are little represented in different ethnobotanical studies because of inadequate data collection methods to record these species; 2) ferns and lycophytes are little represented because of the local perception of their low therapeutic efficacy; and 3) species of ferns and lycophytes are represented in local pharmacopoeias in proportion to the size of their families. We chose rural communities from Chapada do Araripe, Northeast Brazil to test our hypotheses. Data on the medicinal plant repertoires of the communities and on the perceived therapeutic efficacy of ferns were obtained using two different methods, semi-structured interviews associated with free lists and a checklist interview, both applied to local specialists. The resulting data were analyzed differently for each test. In addition, data regarding the total flora x medicinal flora ratio were obtained with a floristic survey and accessing data banks from previous studies performed by our research team. All hypotheses were confirmed, showing that all three factors contributed to the low representation of these plant groups as medicinal resources. The present study showed that free-list interviews are not a good method to access traditional knowledge of medicinal ferns and lycophytes and that the use of visual stimuli can help the memory of the informants, thus making it possible to associate the perceived characteristics with plant use. The results also showed that individuals perceive these plants as inferior therapeutic resources compared to angiosperms, which contributes to knowledge of their use not being transmitted. The final result of the present study was that the distribution of medicinal fern and lycophyte species within families was consistent with the total flora x medicinal flora ratio. This result indicates that even if the most appropriate data collection method was used for the ethnobotanical survey, the number of species would not be as expressive as that of angiosperms.


How do plants feel the heat?
In plants, the heat stress response (HSR) is highly conserved and involves multiple pathways, regulatory networks and cellular compartments. At least four putative sensors have recently been proposed to trigger the HSR. They include a plasma membrane channel that initiates an inward calcium flux, a histone sensor in the nucleus, and two unfolded protein sensors in the endoplasmic reticulum and the cytosol. Each of these putative sensors is thought to activate a similar set of HSR genes leading to enhanced thermotolerance, but the relationship between the different pathways and their hierarchical order is unclear. In this review, we explore the possible involvement of different thermosensors in the plant response to warming and heat stress.


Integrating genomics across drug discovery and development.
The sequencing of the human genome was an exceptional achievement, but it was not an end in itself as it set the foundation for building new knowledge in biology and medicine. The laborious, multifaceted science of drug discovery and development also draws tremendous benefits from mining the human genome and exploiting the large palette of genomic technologies. This article discusses how diverse genomic tools have been used to date and how they will continue to be utilized in the future to impact drug discovery and development. Integrating genomics across drug discovery and development will undoubtedly help to shorten timelines, increase success rates at all stages and ultimately bring the right drugs to the right patients at the right times.


Relationship between the efficiency of muscular work during jumping and the energetics of running.
The running economy of seventeen athletes was studied during running at a low speed (3.3 m X s-1) on a motor-driven treadmill. The net energetic cost during running expressed in kJ X kg-1 X km-1 was on average 4.06. As expected, a positive relationship was found between the energetic cost and the percentage of fast twitch fibres (r = 0.60, n = 17, p less than 0.01). In addition, the mechanical efficiency during two different series of jumps performed with and without prestretch was measured in thirteen subjects. The effect of prestretch on muscle economy was represented by the ratio between the efficiency of muscular work performed during prestretch jumps and the corresponding value calculated in no prestretch conditions. This ratio demonstrated a statistically significant relationship with energy expenditure during running (r = -0.66, n = 13, P less than 0.01), suggesting that the elastic behaviour of leg extensor muscles is similar in running and jumping if the speeds of muscular contraction during eccentric and concentric work are of similar magnitudes.


DNA microarrays on silicon surfaces through thiol-ene chemistry.
The potential of thiol-ene chemistry as a selective strategy to functionalize silicon materials for DNA microarraying is demonstrated and applied to discriminate genetic variations.


Transcriptomes and neurotransmitter profiles of classes of gustatory and somatosensory neurons in the geniculate ganglion.
Taste buds are innervated by neurons whose cell bodies reside in cranial sensory ganglia. Studies on the functional properties and connectivity of these neurons are hindered by the lack of markers to define their molecular identities and classes. The mouse geniculate ganglion contains chemosensory neurons innervating lingual and palatal taste buds and somatosensory neurons innervating the pinna. Here, we report single cell RNA sequencing of geniculate ganglion neurons. Using unbiased transcriptome analyses, we show a pronounced separation between two major clusters which, by anterograde labeling, correspond to gustatory and somatosensory neurons. Among the gustatory neurons, three subclusters are present, each with its own complement of transcription factors and neurotransmitter response profiles. The smallest subcluster expresses both gustatory- and mechanosensory-related genes, suggesting a novel type of sensory neuron. We identify several markers to help dissect the functional distinctions among gustatory neurons and address questions regarding target interactions and taste coding.Characterization of gustatory neural pathways has suffered due to a lack of molecular markers. Here, the authors report single cell RNA sequencing and unbiased transcriptome analyses to reveal major distinctions between gustatory and somatosensory neurons and subclusters of gustatory neurons with unique molecular and functional profiles.


Superhydrophobic surfaces fabricated from nano- and microstructured cellulose stearoyl esters.
Robust, superhydrophobic and self-cleaning films were fabricated using nano- or microstructured cellulose fatty acid esters, which were prepared via nanoprecipitation. The superhydrophobic films could be coated on diverse surfaces with non-uniform shapes by distinct coating techniques.


Estrogen signaling in healthy and tumor brain.
Sex-specific differences in brain organization and function are widely explored in multidisciplinary studies, ranging from sociology and biology to digital modelling. In addition, there is growing evidence that natural or disturbed hormonal environments play a crucial role in the onset of brain disorders and pathogenesis. For example, steroid hormones, but also enzymes involved in steroidogenesis and receptors triggering hormone signaling are key players of gliomagenesis. In the present review we summarize the current knowledge about steroid hormone, particularly estrogens synthesis and signaling, in normal brain compared to the tumor brain. We will focus on two key molecular players, aromatase and the G Protein-Coupled Estrogen Receptor, GPER.


Advance care planning for home health staff: a systematic review.
Advance care planning (ACP) is a process where patients express their wishes regarding their future healthcare. Its importance has been increasingly recognised in the past decade. As increasing numbers of elderly people are living in care homes, the aim of this review was to identify the most effective ACP interventions to train/educate all levels of healthcare professionals working in care homes. A systematic review. Two independent reviewers undertook screening, data extraction and quality assessment. Searched from inception to June 2018: Ovid Medline, Ovid Medline in process, Ovid Embase, Cochrane Central Register of Controlled Trials, EBSCO Cinahl and Ovid PsycINFO. Six studies were included: three before and after studies, one cluster randomised controlled trial (RCT), one non-blinded RCT and one qualitative study. Five studies reported on ACP documentation, three on impact on ACP practice and three studies on healthcare-related outcomes. All quantitative studies reported an improvement in outcomes. In the three studies reporting on health-related outcomes, one showed significant reductions in hospitalisation rate, days and healthcare costs; one reported significant reductions in hospital deaths; and the third showed reductions in hospital days and deaths. A meta-analysis could not be performed due to the heterogeneity of the outcome measures. The included qualitative study highlighted perceived challenges to implementing an educational programme in the care home setting. There is limited evidence for the effectiveness of ACP training for care home workers. More well-designed studies are needed. CRD42016042385 .


Comparative RNA-Seq analysis on the regulation of cucumber sex differentiation under different ratios of blue and red light.
Cucumber (Cucumis sativus L.) is a typical monoecism vegetable with individual male and female flowers, which has been used as a plant model for sex determination. It is well known that light is one of the most important environmental stimuli, which control the timing of the transition from vegetative growth to reproductive development. However, whether light controls sex determination remains elusive. To unravel this problem, we performed high-throughput RNA-Seq analyses, which compared the transcriptomes of shoot apices between R2B1(Red light:Blue light = 2:1)-treated and R4B1(Red light:Blue light = 4:1)-treated cucumber seedlings. Results showed that the higher proportion of blue light in the R2B1 treatment significantly induced the formation of female flowers and accelerated female flowering time in this whole study. The genes related to flowering time, such as flowering locus T (FT) and SUPPRESSOR OF OVEREXPRESSION OF CO1 (SOC1), were up-regulated after R2B1 treatment. Furthermore, the transcriptome analysis showed that up-regulation and down-regulation of specific DEGs (the differentially expressed genes) were primarily the result of plant hormone signal transduction after treatments. The specific DEGs related with auxin formed the highest percentage of DEGs in the plant hormone signal transduction. In addition, the expression levels of transcription factors also changed after R2B1 treatment. Thus, sex differentiation affected by light quality might be induced by plant hormone signal transduction and transcription factors. These results provide a theoretical basis for further investigation of the regulatory mechanism of female flower formation under different light qualities in cucumber seedlings.


Estimation of microbial growth using population measurements subject to a detection limit.
In this paper we develop a maximum likelihood estimation procedure for determining the mean and variance in microbial population size from microbial population measurements subject to a detection limit. Existing estimation methods generally set non-detectable measurements equal to the detection limit and are highly biased. Because changes in the mean and variance in the microbial population size are typical in industrial processes we also outline statistical tests for detecting such changes when measurements are subject to a detection limit, which is critical for process control. In an industrial process there may also potentially be variability in the microbial growth rate due to variation in the microbial strain, environment, and food characteristics. Accordingly, we also present a maximum likelihood procedure for estimating microbial growth model parameters and their variance components from microbial population measurements subject to a detection limit. Such information can be used to generate the mean and variance through time of the microbial population size, which is vital for the application of predictive microbiological models to risk assessment and food product shelf-life estimation.


The use of a Psoroptes ovis serodiagnostic test for the analysis of a natural outbreak of sheep scab.
Sheep scab is a highly contagious disease of sheep caused by the ectoparasitic mite Psoroptes ovis. The disease is endemic in the UK and has significant economic impact through its effects on performance and welfare. Diagnosis of sheep scab is achieved through observation of clinical signs e.g. itching, pruritis and wool loss and ultimately through the detection of mites in skin scrapings. Early stages of infestation are often difficult to diagnose and sub-clinical animals can be a major factor in disease spread. The development of a diagnostic assay would enable farmers and veterinarians to detect disease at an early stage, reducing the risk of developing clinical disease and limiting spread. Serum samples were obtained from an outbreak of sheep scab within an experimental flock (n = 480 (3 samples each from 160 sheep)) allowing the assessment, by ELISA of sheep scab specific antibody prior to infestation, mid-outbreak (combined with clinical assessment) and post-treatment. Analysis of pre-infestation samples demonstrated low levels of potential false positives (3.8%). Of the 27 animals with clinical or behavioural signs of disease 25 tested positive at the mid-outbreak sampling period, however, the remaining 2 sheep tested positive at the subsequent sampling period. Clinical assessment revealed the absence of clinical or behavioural signs of disease in 132 sheep, whilst analysis of mid-outbreak samples showed that 105 of these clinically negative animals were serologically positive, representing potential sub-clinical infestations. This study demonstrates that this ELISA test can effectively diagnose sheep scab in a natural outbreak of disease, and more importantly, highlights its ability to detect sub-clinically infested animals. This ELISA, employing a single recombinant antigen, represents a major step forward in the diagnosis of sheep scab and may prove to be critical in any future control program.


Expression and intracellular localization of Pyk2 in normal and v-src transformed chicken epiphyseal chondrocytes.
The expression and localization of prolin-rich tyrosine kinase 2 (Pyk2) were studied in chick embryo epiphyseal chondrocytes. Two immunoreactive bands were detected in chondrocytes, a major band with an apparent Mr of 123 kDa and a minor band with an apparent Mr of 68 kDa. The major band appears to migrate as a doublet with apparent Mr of 116/123 kDa. Increased levels of the three forms of Pyk2 were observed in v-src transformed chondrocytes as compared to control uninfected chondrocytes. Immunofluorescent staining shows that Pyk2 is clearly visible in the cytosol and in the perinuclear region of control and v-src-chondrocytes and displays a pattern very similar to the distribution of the mitochondrial marker Mito Tracker. More, immunofluorescent staining shows that Pyk2 is nuclear in most chondrocytes. By subcellular fractionation, the p116/123 Pyk2 doublet, was found to be accumulated mainly in the cytoplasm while the p68 Pyk2 form, was found to be accumulated exclusively in the nucleus. The differential nuclear/cytoplasmic distribution of the Pyk2 forms remains unchanged after v-Src-induced transformation. The p68 Pyk2 form could no longer be detected by using a N-terminus domain-specific anti-Pyk2 antibody. Consistently, Pyk2 immunoreactivity was restricted to the cytoplasm of control and v-src transformed chondrocytes. Thus it appears that the p68 Pyk2 form that accumulates in the nucleus has a deletion in the N-terminus region.


The management of chronic ulceration.
The following case report illustrates the long-term difficulties facing many patients with chronic wounds and the management options available.


Bryostatin 1 induces productive Epstein-Barr virus replication in latently infected cells: implications for use in immunocompromised patients.
Bryostatin 1 is a novel anti-tumor agent currently undergoing clinical trial. We investigated the effect of this drug on B-lymphocyte cell lines that carry the Epstein-Barr virus and found that it induces these latently infected cells into the production of transforming virus particles over a wide range of concentrations. These results may have clinical implications, particularly with regard to the use of the drug in the immunocompromised patient.


Genomic surveillance of SARS-CoV-2 in Thailand reveals mixed imported populations, a local lineage expansion and a virus with truncated ORF7a.
Coronavirus Disease 2019 (COVID-19) is a global public health threat. Genomic surveillance of SARS-CoV-2 was implemented in March of 2020 at a major diagnostic hub in Bangkok, Thailand. Several virus lineages supposedly originated in many countries were found, and a Thai-specific lineage, designated A/Thai-1, has expanded to be predominant in Thailand. A virus sample in the SARS-CoV-2 A/Thai-1 lineage contains a frame-shift deletion at ORF7a, encoding a putative host antagonizing factor of the virus.


Stereological parameters from the analysis of the cell micrographs either by manual point-counting methods or by using a semi-automatic system: a BASIC program for ZX-Spectrum personal computer.
A BASIC program is presented which calculates stereological parameters from the data obtained by the analysis of cell micrographs, either by manual point-counting or semi-automatic analysis methods.


[Spinal increase of the Hoffmann reflex by stimulation of the sural nerve at a low intensity: study of the paraplegic].
The effects on the H reflex of stimulating the sural nerve at a low intensity were investigated in 9 paraplegic patients with complete spinal sections. Six delays between the cutaneous and the reflexogenic stimuli were tested: 20, 50, 70, 80, 100 and 120 msec. The results show a very significant increase of the H reflex at delays between 50 and 120 msec. We conclude that the increase of the H reflex observed in normal subjects at the same delays after a sural nerve stimulation is indeed a spinal phenomenon.


A multicenter comparison of adverse reaction profiles of isradipine and enalapril at equipotent doses in patients with essential hypertension.
A multicenter, randomized, double-blind trial compared the safety and efficacy of the dihydropyridine isradipine with the angiotensin-converting enzyme (ACE) inhibitor enalapril given twice daily for mild hypertension. 160 patients received either isradipine (starting at 1.25 mg twice daily) or enalapril (starting at 2.5 mg twice daily) for 10 weeks. The dosage was increased if the average sitting diastolic blood pressure was > 90 mm Hg. Significantly greater mean reductions in systolic blood pressure were seen after 2, 6, and 8 weeks of isradipine. However, by the end of the trial, 83% of patients receiving isradipine and 78% receiving enalapril showed a decrease of at least 5 mm Hg in sitting diastolic blood pressure to a level below 96 mm Hg. Possible or probable drug-related adverse effects were reported in 36% of patients showing a good antihypertensive response to isradipine, and in 30% of those who responded to enalapril. There was a trend for a lower frequency of adverse effects in isradipine non-responders (25%) and a higher frequency in enalapril non-responders (43%). Pruritus, dizziness, edema, and fatigue were reported more often with isradipine, and cough and changed bowel habits were more common with enalapril. The relationship between the pattern of adverse effects and the extent of blood pressure reduction may be dependent on the mechanism of action of a drug. In responders, isradipine and enalapril showed differing patterns, but a similar overall incidence of adverse effects.


Targeting cofactors regeneration in methylation and hydroxylation for high level production of Ferulic acid.
Ferulic acid (FA) is a natural methylated phenolic acid which represents various bioactivities. Bioproduction of FA suffers from insufficient methyl donor supplement and inefficient hydroxylation. To overcome these hurdles, we first activate the S-adenosylmethionine (SAM) cycle in E. coli by using endogenous genes to supply sufficient methyl donor. Then, a small protein Fre is introduced into the pathway to efficiently regenerate FADH2 for the hydroxylation. Remarkably, regeneration of these two cofactors dramatically promotes FA synthesis. Together with decreasing the byproducts formation and boosting precursor supply, the titer of FA reaches 5.09 g/L under fed-batch conditions, indicating a 20-fold improvement compared with the original producing E. coli strain. This work not only establishes a promising microbial platform for industrial level production of FA and its derivatives, but also highlights a convenient and effective strategy to enhance the biosynthesis of chemicals requiring methylation and FADH2-dependent hydroxylation.


Flavonoid glycosides from the stem bark of Margaritaria discoidea demonstrate antibacterial and free radical scavenging activities.
One new flavonoid glycoside, along with three known flavonoid glycosides were isolated from the stem bark of Margaritaria discoidea, which is traditionally used in the management of wounds and skin infections in Ghana. The new flavonoid glycoside was elucidated as hydroxygenkwanin-8-C-[α-rhamnopyranosyl-(1 → 6)]-β-glucopyranoside (1) on the basis of spectroscopic analysis. The isolated compounds demonstrated free-radical scavenging as well as some level of antibacterial activities. Microorganisms including Staphylococcus aureus are implicated in inhibiting or delaying wound healing. Therefore, any agent capable of reducing or eliminating the microbial load present in a wound as well as decreasing the levels of reactive oxygen species may facilitate the healing process. These findings therefore provide some support to the ethnopharmacological usage of the plant in the management of wounds.


Myonuclear apoptosis occurs during early posthatch starvation.
Apoptosis is a naturally occurring process; it is important for the final shape and size of developing tissues, and it is characterized by some morphological features such as plasma membrane blebbing, nuclear breakdown, chromosomal fragmentation and apoptotic bodies followed by phagocytosis. The objective of the study was to evaluate the occurrence of apoptosis in chickens immediately posthatch under fed and starved conditions. Male broiler chickens were or were not provided feed for the first 3 days posthatch. Chickens were killed immediately after hatch, at 1 day of age, at 2 days of age and at 3 days of age. The Pectoralis thoracicus was removed, fixed, dehydrated, cleared and embedded in paraffin. Muscle sections were labeled using terminal deoxynucleotidyl transferase (TdT)-mediated dUTP Nick-End Labeling (TUNEL) for detection of apoptotic nuclei. Body weights were lower (P<0.05) in the starved compared to the fed group at 2 and 3 days posthatch. Myofiber cross-sectional area was only smaller (P<0.05) in the starved compared to the fed birds at 3 days posthatch. TUNEL-positive nuclei were present at all days for the fed and starved groups. The proportion of TUNEL-positive nuclei was higher (P<0.05) for the starved group at day 2 and day 3 posthatch compared to the fed group at 3 days posthatch. Apoptosis is a mechanism that contributes to the smaller myofiber size observed at 3 days posthatch.


Telomere dynamics in cancer progression and prevention: fundamental differences in human and mouse telomere biology.
Cells from the telomerase knockout mouse immortalize with an approximately ten million-fold greater frequency than human cells. In this commentary, Wright and Shay discuss the implications of this difference between mice and men and its relationship to cancer.


Identification and characterization of a minisatellite contained within a novel miniature inverted-repeat transposable element (MITE) of Porphyromonas gingivalis.
Repetitive regions of DNA and transposable elements have been found to constitute large percentages of eukaryotic and prokaryotic genomes. Such elements are known to be involved in transcriptional regulation, host-pathogen interactions and genome evolution. We identified a minisatellite contained within a miniature inverted-repeat transposable element (MITE) in Porphyromonas gingivalis. The P. gingivalis minisatellite and associated MITE, named 'BrickBuilt', comprises a tandemly repeating twenty-three nucleotide DNA sequence lacking spacer regions between repeats, and with flanking 'leader' and 'tail' subunits that include small inverted-repeat ends. Forms of the BrickBuilt MITE are found 19 times in the genome of P. gingivalis strain ATCC 33277, and also multiple times within the strains W83, TDC60, HG66 and JCVI SC001. BrickBuilt is always located intergenically ranging between 49 and 591 nucleotides from the nearest upstream and downstream coding sequences. Segments of BrickBuilt contain promoter elements with bidirectional transcription capabilities. We performed a bioinformatic analysis of BrickBuilt utilizing existing whole genome sequencing, microarray and RNAseq data, as well as performing in vitro promoter probe assays to determine potential roles, mechanisms and regulation of the expression of these elements and their affect on surrounding loci. The multiplicity, localization and limited host range nature of MITEs and MITE-like elements in P. gingivalis suggest that these elements may play an important role in facilitating genome evolution as well as modulating the transcriptional regulatory system.


Therapeutic potential of functionalized siRNA nanoparticles on regression of liver cancer in experimental mice.
Short interfering RNA (siRNA) possesses special ability of silencing specific gene. To increase siRNA stability, transportation and its uptake by tumor cells, effective delivery to the appropriate target cells is a major challenge of siRNA-based therapy. In the present study, an effective, safe and biocompatible survivin siRNA encapsulated, GalNAc decorated PEGylated PLGA nanoconjugates (NCs) viz., GalNAc@PEG@siRNA-PLGA were engineered and their synergistic antitumor efficacy was evaluated for targeted delivery in HCC bearing experimental mice. GalNAc@PEG@siRNA-PLGA NCs were characterized for size, bioavailability, toxicity and biocompatibility. Their antitumor potential was evaluated considering gene silencing, apoptosis, histopathology and survival of treated mice. Exceptional accumulation of hepatocytes, reduction in survivin expression and prominent regression in tumor size confirmed the ASGPR-mediated uptake of ligand-anchored NCs and silencing of survivin gene in a targeted manner. Increased DNA fragmentation and potential modulation of caspase-3, Bax and Bcl-2 factors specified the induction of apoptosis that helped in significant inhibition of HCC progression. The potential synchronous and tumor selective delivery of versatile NCs indicated the effective payloads towards the target site, increased apoptosis in cancer cells and improved survival of treated animals.


The SLAMF3 rs509749 polymorphism correlates with malignant potential in multiple myeloma.
The signaling lymphocytic activation molecule family 3 (SLAMF3) is highly expressed on plasma cells from patients with multiple myeloma (MM) and induces high malignant potential by ERK signaling mediated via the interaction with adaptor proteins SHP2 and GRB2. This study focused on the single-nucleotide polymorphism (SNP) of the SLAMF3 gene (rs509749, 1804A>G, M602V) in MM. The SNP G allele was a major type, and the frequencies of the GG, GA, and AA genotypes were 61.8%, 29.4%, and 8.8%, respectively, in patients with MM, which was almost the same as in healthy the control group in the Japanese population. Interestingly, patients with GG genotypes had significantly shorter overall survival times than patients with GA/AA genotypes. Consistent with those results, SLAMF3-overexpressing KMS-34 cells with the G allele (V602) had higher cell proliferation potential and were more resistant to anti-MM agents than those with the A allele (M602). When those cells were subcutaneously inoculated into NOG mice, tumor sizes in mice receiving V602 cells rapidly increased, and survival was significantly shorter than in mice injected with M602 cells. Furthermore, SLAMF3 V602 molecules bound more tightly to SHP2 and GRB2, with increased SHP2 and ERK phosphorylation compared with M602 cells. The mRNA expression of cell cycle-related genes (CCND1 and CCNE1) and anti-apoptotic genes (BCL2L and p21) was increased in V602 cells compared with M602 cells. The results thus suggested that the G allele of SLAMF3 SNP rs509749 may be associated with MM disease progression.


Severe progression of ALS/MND after intervertebral discectomy.
We observed seven patients who developed their first signs and symptoms of motor neuron disease together with signs of protrusion/prolapse of intervertebral disc. The age of the patients was between 55 and 67, of which one female and six male patients. All of them suffered from cervical spine pain or low back pain. The female patient and one male patient developed weakness in the small feet muscles as initial symptom and they complained of paresthesia along dermatomes L5S1 and of severe pain. The other five patients developed wasting of the hands muscles. They had a rather mild pain in the cervical spine and early morning paresthesia as well as severe causalgia along dermatomes C5C6 or C6C7. After the diagnosis of compressive radiculopathy in all patients, they underwent surgical treatment and very soon developed very severe progression of muscle wasting which included muscles of limbs, trunk and bulbar innervated muscles with signs and symptoms of lower and upper motor neuron lesion. Five patients died from 12 to 15 months after surgical treatment and two patients are still living.


Quality control: proteins and organelles.
This review summarizes materials on the mechanisms of intracellular degradation of proteins whose topogenesis is disturbed at one stage or another. Chaperone and proteolytic systems involved in this process in the endoplasmic reticulum, mitochondria, and chloroplasts of eucaryotic cells as well as those in distinct subcellular compartments of procaryotic cells are considered. The available data suggest that living cells contain numerous systems keeping under control both folding of newly synthesized and newly imported polypeptide chains and their incorporation into heterooligomeric complexes. The point of view is elaborated that organelle formation is controlled not only at the level of individual protein molecules but also at the supermolecular level when whole organelles incapable of carrying out their integral key functions become targets for partial or total elimination. This type of control is realized through an autophagic mechanism involving lysosomes/vacuoles.


Building innovative, inclusive and resilient global value chains.
Future is an unpredictable certainty that everyone would like to control. With all the advancements of technology, the Future remains out of grasp. However, the closest thing that one can do to be there is to prepare oneself in such a way that no matter what the Future will be, one is able to face it. With anything that is unknown, the preparation needs to be as broad-based as possible to be able to handle different possibilities. The current situation across the world is such a situation with unpredictable certainty with the spread of the different variants of the COVID-19 virus. Evidence-based research has revealed that the strategic ability of some Global Value Chains (GVC) has facilitated recovery from inevitable vulnerabilities and unexpected events, such as the COVID-19 pandemic more effectively than others. This has more recently triggered a policy debate about Innovative, Inclusive and Resilient Value Chains. Innovative, Inclusive and Resilient Value Chains are in a way broad-based preparation that aim at developing the adaptive capability of them to prepare for the unexpected events and to respond to disruptions and recover from them. Within this context, this special issue will analyse the process of building Innovative, Inclusive and Resilient Value Chains, and their impact on the socio-economic development of Asia and beyond.


ABIOMED BVS 5000 system: repair of venous cannulation site for excessive bleeding.
The most common morbidity of the ABIOMED (Danvers, MA) left ventricular assist device is severe hemorrhage. Severe bleeding around the left atrial cannulation site can be repaired easily with the proper technique.


Pharmacological treatment to augment hole board habituation in prenatal Vitamin D-deficient rats.
Neurocognitive impairment has consistently been considered a central and stable feature of schizophrenia. There is much controversy about the effects of neuroleptics on neurocognitive deficits. Thus, further investigations are needed to clarify the pathological substrate of cognitive deficits in schizophrenia as well as to identify pharmacological tools for treatment. Transient prenatal Vitamin D deficiency is considered a developmental model in schizophrenia research. Recently, it was reported that prenatal Vitamin D-depleted rats showed a habituation deficit in the hole board. Here, we tested the effect on hole board habituation of haloperidol (Hal, 0.075 mg/kg, i.p.), risperidone (Ris, 0.2 mg/kg, i.p.) and the mGluR5 agonist CHPG (0.1 mg, i.c.v.) after subchronic treatment. Hal was found to impair habituation in control animals, Ris restored hole board habituation, whereas Hal and CHPG normalised hole board habituation in the deplete animals completely. The results of the study demonstrate that (i) the Vitamin D model might be a valuable tool in the study of neurodevelopmental aspects of schizophrenia, (ii) the model is sensitive in detecting the effect of antipsychotic drugs and (iii) the model appears to be sensitive in differentiating between typical and atypical antipsychotic drug.


On the ab initio solution of the phase problem or macromolecules at very low resolution. II. Generalized likelihood based approach to cluster discrimination.
The multisolution strategies for direct phasing at very low resolution, such as the few atoms model technique, result in a number of alternative phase sets, each of them arising from a cluster of closely related models. Use of a Monte-Carlo type computer procedure is suggested to choose between the possible phase sets. It consists of generating a large number of pseudo-atom models inside the mask defined by a trial phase set and the use of histograms of magnitude correlation to evaluate the masks. It is shown that the procedure may be considered as a generalization of the statistical maximum-likelihood principle and may be used as a powerful supplementary tool in the likelihood-based approaches to the phase problem solution.


Memantine for Refractory Obsessive-Compulsive Disorder: Protocol for a Pragmatic, Double-blind, Randomized, Parallel-Group, Placebo-Controlled, Monocenter Trial.
Obsessive-compulsive disorder (OCD) is a psychiatric syndrome characterized by unwanted and repetitive thoughts and repeated ritualistic compulsions for decreasing distress. Symptoms can cause severe distress and functional impairment. OCD affects 2% to 3% of the population and is ranked within the 10 leading neuropsychiatric causes of disability. Cortico-striatal-thalamo-cortical circuitry dysfunction has been implicated in OCD, including altered brain activation and connectivity. Complex glutamatergic signaling dysregulation within cortico-striatal circuitry has been proposed in OCD. Data obtained by several studies indicate reduced glutamatergic concentrations in the anterior cingulate cortex, combined with overactive glutamatergic signaling in the striatum and orbitofrontal cortex. A growing number of randomized controlled trials have assessed the utility of different glutamate-modulating drugs as augmentation medications or monotherapies for OCD, including refractory OCD. However, there are relevant variations among studies in terms of patients' treatment resistance, comorbidity, age, and gender. At present, 4 randomized controlled trials are available on the efficacy of memantine as an augmentation medication for refractory OCD. Our study's main purpose is to conduct a double-blind, randomized, parallel-group, placebo-controlled, monocenter trial to assess the efficacy and safety of memantine as an augmentative agent to a selective serotonin reuptake inhibitor in the treatment of moderate to severe OCD. The study's second aim is to evaluate the effect of memantine on cognitive functions in patients with OCD. The third aim is to investigate if responses to memantine are modulated by variables such as gender, symptom subtypes, and the duration of untreated illness. Investigators intend to conduct a double-blind, randomized, parallel-group, placebo-controlled, monocenter trial to assess the efficacy and safety of memantine as an augmentative agent to a selective serotonin reuptake inhibitor in the treatment of patients affected by severe refractory OCD. Participants will be rated via the Yale-Brown Obsessive Compulsive Scale at baseline and at 2, 4, 6, 8, 10, and 12 months. During the screening period and T4 and T6 follow-up visits, all participants will undergo an extensive neuropsychological evaluation. The 52-week study duration will consist of 4 distinct periods, including memantine titration and follow-up periods. Recruitment has not yet started. The study will be conducted from June 2023 to December 2024. Results are expected to be available in January 2025. Throughout the slow-titration period, we will observe the minimum effective dose of memantine, and the follow-up procedure will detail its residual efficacy after drug withdrawal. The innovation of this research proposal is not limited to the evaluation of the efficacy and safety of memantine as an augmentation medication for OCD. We will also test if memantine acts as a pure antiobsessive medication or if memantine's ability to improve concentration and attention mimics an antiobsessive effect. ClinicalTrials.gov NCT05015595; https://clinicaltrials.gov/ct2/show/NCT05015595. PRR1-10.2196/39223.


Technical note: Influence of the drying position and time on the persistence of gunshot residues on fabrics.
The influence of the drying position and time on the persistence of gunshot residues (GSR) on fabrics was investigated. Powder tattooing from a 40 cm shooting distance on targeted fabrics were slightly wetted using a spray and dried for 3 h or 48 h in horizontal or vertical positions. The GSR particles were visualised using IR fluorescence with a Video Spectral Comparator (VSC) and automatically counted with a software before the wetting and after the drying stages. While a significant rate of GSR particles (up to 22%) were lost, it was mainly due to the wetting procedure rather than the drying stage. No statistically significant difference was observed between the drying positions, indicating that both drying positions can be used in practice to dry slightly wet fabrics. The drying time had no influence on the loss, and the GSR distribution was not significantly influenced by either factor (i.e., time and position).


Long-duration upper extremity surgery under brachial plexus block combined with intravenous dexmedetomidine sedation without an anesthesiologist.
Dexmedetomidine (DEX) provides a unique conscious sedation without respiratory depression. We examined the usefulness of intravenous (IV) DEX sedation combined with brachial plexus block for long-duration upper extremity surgery without an anesthesiologist. We retrospectively reviewed 90 limbs of 86 patients and measured the actual operative time course in detail. The adverse events and the patient-reported outcomes regarding intraoperative pain and depth of sedation were evaluated. The mean total time of the operation, tourniquet use, and the IV DEX sedation were 150 min, 132 min, and 117 min, respectively. The mean time between discontinuation of IV DEX sedation and completion of the operation was 51 min. The intraoperative adverse events involved bradycardia (21%), hypotension (18%), and oxygen desaturation (3%). The mean visual analog scale scores of pain during brachial plexus block, surgical site pain, tourniquet pain, and depth of the sedation were 23.4 mm, 0.14 mm, 4.2 mm, and 6.6 mm, respectively. Furthermore, 96% patients expressed a preference for receiving anesthesia as brachial plexus block with IV DEX sedation. Long-duration upper extremity surgery, even longer than 2 h, was feasible under brachial plexus block combined with IV DEX sedation without an anesthesiologist. For patients with low blood pressure and/or low heart rate, it is recommended to adjust the continuous infusion of IV DEX to less than 0.4 µg/kg/h. To ensure that the patients are able to promptly leave the operating room fully awake, IV DEX infusion should be stopped at least 30 min before finishing the operation.


Therapeutic efficacy of tumor-targeted IL2 in LTalpha(-/-) mice depends on conditioned T cells.
An effective immunological eradication of tumors by the adaptive immune system depends on T cell priming, expansion of specific T cells and their effector function. It has been shown that either step may be impaired in the tumor-bearing host, and several strategies have been used to improve antitumor immune responses. In this regard, tumor-targeted IL2 therapy leads to the destruction of established melanoma metastases in fully immune competent mice as previously demonstrated. This effect has been attributed, but never directly confirmed, to the boost of antigen-experienced T cells. To this end, we demonstrate the absence of any antitumor effect of targeted IL2 in mice characterized by an impaired priming of T cell responses. Notably, in these animals tumor-targeted IL2 therapy induced tumor regression only after adoptive transfer of tumor-conditioned splenocytes. A detailed analysis revealed that T cells present within the transferred splenocytes were actively participating in the immune response as these were clonally expanded after targeted IL2 therapy. In summary, we demonstrate here that in LTalpha(-/-) mice lacking sufficient numbers of tumor-specific T cells only the passive transfer of such cells prior to therapy restores the efficacy of tumor-targeted IL2 therapy. Thus, the antitumor effect of tumor-targeted IL2 is indeed based on the boost of pre-existing T cell responses.


Nanostructured medical device coatings based on self-assembled poly(lactic-co-glycolic acid) nanoparticles.
Here we present a new method for providing nanostructured drug-loaded polymer films which enable control of film surface morphology and delivery of therapeutic agents. Silicon wafers were employed as models for implanted biomaterials and poly(lactic-co-glycolic acid) (PLGA) nanoparticles were assembled onto the silicon surface by electrostatic interaction. Monolayers of the PLGA particles were deposited onto the silicon surface upon incubation in an aqueous particle suspension. Particle density and surface coverage of the silicon wafers were varied by altering particle concentration, incubation time in nanoparticle suspension and ionic strength of the suspension. Dye loaded nanoparticles were prepared and assembled to silicon surface to form nanoparticle films. Fluorescence intensity measurements showed diffusion-controlled release of the dye over two weeks and atomic force microscopy (AFM) analysis revealed that these particles remained attached to the surface during the incubation time. This work suggests that coating implants with PLGA nanoparticles is a versatile technique which allows drug release from the implant surface and modulation of surface morphology.


Estrogen-dependent expression of sine oculis homeobox 1 in the mouse uterus during the estrous cycle.
The sine oculis homeobox 1 (SIX1) is a member of the Six gene family. SIX1 is involved in tissue development by regulating proliferation, apoptosis, and differentiation. However, function of SIX1 in the uterus remains unknown. Here, we found that Six1 expression is regulated along the estrous cycle in mouse uterus. Six1 expression was significantly increased at estrus stage and decreased at the rest of stages. SIX1 is detected in the luminal and glandular epithelium of uterine endometrium at the estrus stage. Estrogen injection increased Six1 expression in the ovariectomized mouse uterus, whereas progesterone had no effect on its expression. Estrogen receptor antagonist inhibited estrogen-induced Six1 expression. Our findings imply that SIX1 may play a role as an important regulator to orchestrate the dynamic of uterine endometrium in response to estrogen level during the estrous cycle. These results will give us a better understanding of uterine biology.


Paraquat induces cyclooxygenase-2 (COX-2) implicated toxicity in human neuroblastoma SH-SY5Y cells.
Paraquat produces dopaminergic pathologies of Parkinson's disease, in which cyclooxygenase-2 (COX-2) is implicated. However, it is unclear whether paraquat induces toxicity within dopaminergic neurons through COX-2. To address this, human neuroblastoma SH-SY5Y cells were treated with paraquat and then the involving mechanism of COX-2 was investigated. We initially examined the involvement of COX-2 in paraquat-induced toxicity. Data suggest that COX-2 is implicated in paraquat-induced reduction of viability in SY5Y cells. Then, to confirm the presence of COX-2 in SY5Y cells, we examined COX-2 mRNA and protein levels, which are regulated by NF-κB. Data indicate that paraquat activates NF-κB and up-regulates COX-2. We then checked quinone-bound proteins as quinones produced by COX-2 bind to intracellular proteins. Paraquat obviously forms quinone-bound proteins, in particular, quinone-bound DJ-1 and this formation is attenuated by meloxicam. Finally, we investigated antioxidant system including nuclear factor erythroid-related factor 2 (Nrf2), gamma glutamylcysteine synthetase (γGCS), and glutathione (GSH) as DJ-1 is linked to Nrf2 and Nrf2 regulates γGCS expression and γGCS is a GSH synthesis enzyme. Paraquat decreases protein levels of Nrf2 and γGCS and intracellular GSH level and these decreases are alleviated by meloxicam. Therefore, collectively, our data indicate that paraquat induces COX-2 implicated toxicity in SY5Y cells. In conclusion, current findings support the idea that paraquat might produce toxicity in dopaminergic neurons through COX-2.


Effects of arecoline and cholinesterase inhibitors on cyclic guanosine 3',5'-monophosphate and adenosine 3'.5'-monophosphate in mouse brain.
In mice, Arecoline in vivo dose-dependently increased the cGMP concentrations of the cerebellum and the "cereberum" (= parts of cortex, hippocampus, hypothalamus, thalamus, striatum and midbrain) without influencing thecAMP levels. The cholinesterase inhibitors paraoxon and physostigmine caused an elevation only in "cerebrum", whereas the cGMP content of the cerebellum even decreased. Pretreatment with atropine prevented the rise in cGMP levels as well as the symptoms of cholinergic stimulation elicited by arecoline or paraoxon. Diazepam reduced cGMP levels below control values and blocked the effect of arecoline, while typical symptoms due to arecoline, e.g., tremor and salivation remained unaffected. The tripeptide prolyl-leucyl-glycinamide (MIF) had no effect on either cGMP values or the peripheral signs of cholinergic stimulation elicited by arecoline. The results show that elevation of cGMP in the central nervous system caused by cholinomimetic agents can be prevented not only by cholinolytics, blocking muscarinic receptors but also by influencing other mechanisms to be discussed.


Influence of the temperature, volume and type of solution in the mercury vaporization of dental amalgam residue.
One of the qualitative methods for the identification of mercury vapor is what it occurs as a way of chemical reaction between palladium chloride and metallic mercury. Palladium chloride ribbons with yellowish coloration put in contact with the vaporized mercury of dental amalgam residue, liberates palladium and forms mercury chloride in your surface, and starts to have black coloration; this form identify the presence of the mercury vapor in the system. This work studies the influence of temperature, volume and type of barrier-solution in the vaporization of mercury during the period of storage of dental amalgam residues, aiming to establish the best conditions for storage of these residues. It was found that for all tested solutions, the longest storage times without any occurrence of mercury vaporization were obtained in the lowest temperatures tested and the largest solution volumes of barrier-solution. The radiographic effluent presented bigger efficacy in the reduction of the volatilization, increasing the period when the residue was stored, however the analysis of this solution after the vaporization test showed the presence of organic mercury. These results show that water is the most efficient barrier against the vaporization of mercury, since it did not result in organic mercury formation in the effluent solution from the storage process.


Do zirconia dental implants present better clinical results than titanium dental implants? A systematic review and meta-analysis.
The purpose of this systematic review is to determine if the zirconia implants present better clinical results when compared to titanium implants. Searches were conducted in 5 databases including, until March 2022, by 2 independent reviewers, according to the inclusion and exclusion criteria established in the study and according whit this question: Do zirconia dental implants present better clinical results than titanium dental implants? 3235 studies were initially found in the researched databases. 03 randomized clinical trials were included in this systematic review and meta-analysis. A total of 71 patients with 192 implants (87 titanium and 105 zirconia) were evaluated, showing an effectiveness of 87,4% and 78,1% respectively and there was no statistically significant difference in terms of survival rate in the meta-analysis (P = 0.70; I2 = 0%). Still in the meta-analysis, there was no statistically significant difference between titanium and zirconia implants in relation to the pink esthetich score or bleeding on probing, however, a favorable difference was observed for titanium in relation to marginal bone loss (P = 0.001; I2 = 0%). None of the studies evaluated had a low risk of bias. Oral rehabilitation with zirconia implants showed no advantages over titanium in this systematic review. However, the small number of studies included and the uncertain risk of bias may raise doubts in this interpretation and the results should be analyzed with caution. New studies with greater methodological rigor, follow-up time and number of interventions should be performed in order to safely determine the indication for the use of zirconia implants.


Bees assess pollen returns while sonicating Solanum flowers.
Can bees accurately gauge accumulating bodily pollen as they harvest pollen from flowers? Several recent reports conclude that bees fail to assess pollen harvest rates when foraging for nectar and pollen. A native nightshade (Solanum elaeagnifolium Cavanilles) that is visited exclusively for pollen by both solitary and social bees (eg. Ptiloglossa and Bombus) was studied in SE Arizona and SW New Mexico. The flowers have no nectaries. Two experiments were deployed that eliminated "pollen feedback" to the bees by experimentally manipulating flowers prior to bee visits. The two methods were 1) plugging poricidal anthers with glue and 2) emptying anthers of pollen by vibration prior to bee visitation. Both experiments demonstrated that bees directly assess pollen harvest on a flower-by-flower basis, and significantly tailor their handling times, number of vibratile buzzes per flower and grooming bouts according to the ongoing harvest on a given flower. In comparison to experimental flowers, floral handling times were extended for both Bombus and Ptiloglossa on virgin flowers. Greater numbers of intrafloral buzzes and numbers of times bees groomed pollen and packed it into their scopae while still on the flower were also more frequent at virgin versus experimental flowers. Flowers with glued andreocia received uniformly brief visits from Bombus and Ptiloglossa with fewer sonications and virtually no bouts of grooming. Curtailed handling with few buzzes and grooms also characterized visits to our manually harvested flowers wherein pollen was artificially depleted. Sonicating bees respond positively to pollen-feedback while harvesting from individual flowers, and therefore we expect them to adjust their harvesting tempo according to the currency of available pollen (standing crop) within Solanum floral patches.


Atypical and incomplete pulmonary hypertrophic osteoarthropathy in the left distal femur: a case report.
Pulmonary hypertrophic osteoarthropathy (PHO) is a rare paraneoplastic syndrome that mainly occurs in patients with lung cancer. Most symptoms occur symmetrically, and unilateral symptoms without clubbing are infrequent. This report presents the case of a rare atypical symptom that was highly suspected of being PHO. A 77-year-old woman with swelling and severe pain in the left femur for 2 months was referred to our hospital. Radiography revealed a remarkably osteogenic thickening and sclerotic lesion in her distal femur. Preliminary diagnoses of malignant bone tumor and hematological tumor were made based on laboratory test results, radiological examination, and clinical manifestation. A needle biopsy was performed, which ruled out the diagnosis of malignant bone tumors. A low-grade bone tumor was still suspected. After that, en bloc resection was performed, followed by replacement of the femur with a mega-prosthesis. Pathological analysis revealed no malignant tumor cells, and immunohistochemical staining for CDK4 and MDM2 yielded negative results. Meanwhile, pulmonary large cell carcinoma was identified on biopsy. Based on published studies, a diagnosis of atypical PHO was made according to clinical and imaging manifestations. This is an infrequent case of PHO with unilateral symptoms in the left femur. When clinical manifestations and radiological findings are inconsistent with the pathological results, the possibility of benign lesions with malignant clinical manifestations or imaging features should be carefully considered.


Accuracy of a RT-qPCR SARS-CoV-2 detection assay without prior RNA extraction.
The current COVID-19 pandemic constitutes a threat to the population worldwide with over 21 million infected people. There is an urgent need for the development of rapid and massive detection tools as well as the identification and isolation of infected individuals. we sought to evaluate different RT-qPCR kits and protocols to evaluate the best approach to be used omitting an RNA extraction step. We have investigated the sensitivity and performance of different commercially available RT-qPCR kits in detecting SARS-CoV-2 using 80 extracted RNA and NSS from COVID-19 diagnosed patients. We evaluated the ability of each kit to detect viral RNA from both kit-extracted or directly from a pre-boiled NSS observing that direct RNA detection is possible when Ct values are lower than 30 with the three kits tested. Since SARS-CoV-2 testing in most locations occurs once COVID-19 symptoms are evident and, therefore, viral loads are expected to be high, our protocol will be useful in supporting SARS-CoV-2 diagnosis, especially in America where COVID-19 cases have exploded in the recent weeks as well as in low- and middle-income countries, which would not have massive access to kit-based diagnosis. The information provided in this work paves the way for the development of more efficient SARS-CoV-2 detection approaches avoiding an RNA extraction step.


Mitochondrial nitrite reduction coupled to soluble guanylate cyclase activation: lack of evidence for a role in the bioactivation of nitroglycerin.
Reduction of nitrite to nitric oxide (NO) by components of the mitochondrial respiratory chain may link nitroglycerin biotransformation by mitochondrial aldehyde dehydrogenase (ALDH2) to activation of soluble guanylate cyclase (sGC). We used purified sGC as detector for NO-like bioactivity generated from nitrite and GTN by isolated heart and liver mitochondria. Exogenous NADH caused a pronounced increase in oxygen consumption that was completely inhibited by myxothiazol and cyanide. Oxygen depletion of cardiac mitochondria by NADH was accompanied by activation of sGC and cyanide-sensitive formation of NO. Mitochondrial biotransformation of nitroglycerin was sensitive to ALDH2 inhibitors and coupled to sGC activation but not affected by respiratory substrates or inhibitors. Our data suggest that cytochrome c oxidase catalyzes reduction of nitrite to NO at low O(2) tension but argue against the involvement of this pathway in mitochondrial bioactivation of nitroglycerin.


Acquisition of generalized telephone use by students with moderate and severe mental retardation.
This study examines the effects of one approach for selecting teaching examples on the development of generalized telephone skills with moderately and severely mentally retarded high school students. Four subjects were taught to make and receive telephone calls within a counterbalanced multiple baseline design. The primary dependent variable was generalization of telephone skills to nontrained telephone situations in home, school, and community settings. Results document the effectiveness and efficiency of the training approach. An eighteen-month validation assessment also shows that telephone use continued as a regular part of each student's lifestyle. The instructional implications of these results are discussed as well as methodological implications for applied research on generalization.


Mitochondrial proteome analysis reveals depression of the Ndufs3 subunit and activity of complex I in diabetic rat brain.
Type-1 diabetes resulting from defective insulin secretion and consequent hyperglycemia, is associated with "diabetic encephalopathy." This is characterized by brain neurophysiological and structural changes resulting in impairment of cognitive function. The present proteomic analysis of brain mitochondrial proteins from streptozotocin-induced type-1 diabetic rats, shows a large decrement of the Ndufs3 protein subunit of complex I, decreased level of the mRNA and impaired catalytic activity of the complex in the diabetic rats as compared to controls. The severe depression of the expression and enzymatic activity of complex I can represent a critical contributing factor to the onset of the diabetic encephalopathy in type-1 diabetes.


Risk Factors for Development of Chronic Kidney Disease in Cats.
Identification of risk factors for development of chronic kidney disease (CKD) in cats may aid in its earlier detection. Evaluation of clinical and questionnaire data will identify risk factors for development of azotemic CKD in cats. One hundred and forty-eight client-owned geriatric (>9 years) cats. Cats were recruited into the study and followed longitudinally for a variable time. Owners were asked to complete a questionnaire regarding their pet at enrollment. Additional data regarding dental disease were obtained when available by development of a dental categorization system. Variables were explored in univariable and multivariable Cox regression models. In the final multivariable Cox regression model, annual/frequent vaccination (P value, .003; hazard ratio, 5.68; 95% confidence interval, 1.83-17.64), moderate dental disease (P value, .008; hazard ratio, 13.83; 95% confidence interval, 2.01-94.99), and severe dental disease (P value, .001; hazard ratio, 35.35; 95% confidence interval, 4.31-289.73) predicted development of azotemic CKD. Our study suggests independent associations between both vaccination frequency and severity of dental disease and development of CKD. Further studies to explore the pathophysiological mechanism of renal injury for these risk factors are warranted.