For the long run: maintaining germinal niches in the adult brain.
The adult mammalian brain retains neural stem cells that continually generate new neurons within two restricted regions: the subventricular zone (SVZ) of the lateral ventricle and the dentate gyrus subgranular zone (SGZ) of the hippocampus. Though these cellular populations are spatially isolated and subserve different brain systems, common themes begin to define adult neurogenic niches: (1) astrocytes serve as both stem cell and niche cell, (2) a basal lamina and concomitant vasculogenesis may be essential components of the niche, and (3) "embryonic" molecular morphogens and signals persist in these niches and play critical roles for adult neurogenesis. The adult neurogenic niches can be viewed as "displaced" neuroepithelium, pockets of cells and local signals that preserve enough embryonic character to maintain neurogenesis for life.


Creating a bicuspid valve from the aortic wall: a new surgical approach on aortic valve disease (in vitro study).
We described a new technique (called 'bicuspidization'), which is performed by using autogenous material, without replacement of the aortic valves for the surgical treatment of aortic stenosis and/or insufficiency and tested it in in vitro sheep model. Different stress conditions were simulated by applying three different flow patterns (hemodynamic challenge tests) successively by using a centrifugal pump. It was demonstrated that the competency of the new bicuspid valves was excellent (zero insufficiency). There was a 10-11 mm Hg-increase on trans-valvular gradient comparing the normal hearts. The autogenous bicuspid valve has not blocked the way of the coronary flow in the closed position.


A language for nursing: furthering the debate.
Continuing the debate on language for nursing, Paul Crawford and Brian Brown argue that merely having a common sense understanding of language is inadequate.


Postural effects on muscle nerve sympathetic activity in man.
1. Pulse-synchronous bursts of multi-unit sympathetic activity (MSA) were recorded in peroneal muscle nerve fascicles in eight healthy subjects when lying, sitting and standing. The sympathetic activity was quantitated by counting the number of bursts in the mean voltage neurogram/min. Postural changes were analysed by considering the total activity to be a product of the number of bursts in relation to the number of heart beats (burst incidence) and the heart rate.2. In lying there were large interindividual differences in total activity, but for all subjects the activity increased when going from lying to sitting and from sitting to standing. With a few exceptions the increase between the lying and sitting postures was associated with an increase in both burst incidence and heart rate whereas between the sitting and standing postures there was an increase in heart rate but on the average no change in burst incidence.3. When going from lying to sitting or from sitting to standing the magnitude of the change in burst incidence was inversely related to the initial burst incidence so that subjects with low initial values usually showed greater increases in burst incidence than subjects with high initial values. Some subjects with high initial values decreased their burst incidence.4. With changes in postures there was an inverse linear relationship between the fraction of the change in MSA associated with a change in burst incidence and the fraction associated with a change in heart rate. An increase in total activity could be obtained by changing only burst incidence, by increasing heart rate without changing burst incidence, or by appropriate changes in both parameters. The slope of the regression line was -0.53 indicating that for adequate postural compensation fewer additional bursts were required when the compensatory response involved an increase in heart rate rather than an increase in only burst incidence.5. It is suggested that an impairment of the ability to regulate heart rate will make subjects with high burst incidence in the lying position orthostatically more vulnerable than those with low burst incidence.6. Shortly after standing up one subject developed bradycardia and subsequently fainted. The nerve recording was maintained until the subject collapsed. During the initial bradycardia no sympathetic bursts occurred suggesting that the syncope was associated with an interruption of normal baroreflex feedback between blood pressure and sympathetic outflow.


Small-Boat Noise Impacts Natural Settlement Behavior of Coral Reef Fish Larvae.
After a pelagic larval phase, settlement-stage coral reef fish must locate a suitable reef habitat for juvenile life. Reef noise, produced by resident fish and invertebrates, provides an important cue for orientation and habitat selection during this process, which must often occur in environments impacted by anthropogenic noise. We adapted an established field-based protocol to test whether recorded boat noise influenced the settlement behavior of reef fish. Fewer fish settled to patch reefs broadcasting boat + reef noise compared with reef noise alone. This study suggests that boat noise, now a common feature of many reefs, can compromise critical settlement behavior of reef fishes.


Petrosquamosal sinus in the temporal bone as a cause of pulsatile tinnitus: a radiological detection.
We report a newly evidenced cause of venous pulsatile tinnitus--the petrosquamosal sinus in the temporal bone. We also present the case of a 45-year-old woman who presented with an incapacitating objective pulsatile tinnitus in the left ear for 10 years. The radiology evidenced a petrosquamosal sinus in the air cells of the left temporal bone. The symptoms of pulsatile tinnitus disappeared completely after surgical treatment.


Demonstration of immunoglobulin-secreting cells in a sensitive reversed hemolytic plaque assay.
A sensitive modification of a reversed hemolytic plaque assay demonstrating individual immunoglobulin-secreting cells (ISC) is presented. The test is performed by adding test cells to a monolayer of indicator sheep erythrocytes coated with an IgG fraction of rabbit antiserum against the F(ab')2 portion of human immunoglobulins (Ig). After having added a developing antiserum and complement, hemolytic plaques with a central ISC could be counted in an inverted microscope. In addition, when ISC were killed and fixed in situ in the monolayer, the cells could be further studied by immunofluorescence of their cytoplasmic Ig.


Subcranial Approach: A Straightforward Approach to the Anterior Fossa Floor: 2-Dimensional Operative Video.
Subcranial approach is a versatile keyhole approach mainly indicated to the tumors of the anterior fossa and midline invasive tumors from the nasal cavity and paranasal sinus. 1-5 Endoscopic endonasal video assistance enhances the exposure and the safety of the approach. Preoperative images depicted the size of the frontal sinuses and the relations of the lesions with frontal, ethmoid, and orbits. After performing a bifrontal scalp flap and a pericranial flap, periorbits are dissected from the superior and medial orbital rims. After frontonasal osteotomy, we drill the posterior wall of the frontal sinus. Avoiding disruption of the cantal ligaments prevents telecantus. Watertight closure of the dura with temporal fascia graft and reinforcement with the pericranial flap makes cerebrospinal fluid leak occurrence very rare. Subcranial approach is our preferred approach for the tumors of the anterior fossa floor and the midline paranasal invasive tumors. This keyhole approach through a relatively small frontoethmoidal craniotomy combines the advantages of the regular craniotomies but with no manipulation of the frontal lobes. An advantageous inferior angle of view similar of the pure endonasal endoscopical approach is achieved, but better than in the pure endoscopical approaches, the subcranial approach allows a direct wider exposure and a superior watertight reconstruction of the anterior fossa floor.The patients consented to the procedure and to the publication of his/her image.


Comparison of sirolimus-eluting stent and paclitaxel-eluting stent for long-term cardiac adverse events in diabetic patients: the Korean Multicenter Angioplasty Team (KOMATE) Registry.
There is some controversy on long-term cardiac outcomes between sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) in diabetes mellitus (DM). We compared cardiac adverse events after SES and PES implantation in patients with DM over a period of 3 year. A total of 634 patients with DM treated with SES (n = 428) or PES (n = 206) were consecutively enrolled in the KOMATE registry from 2003 to 2004. We assessed major adverse cardiac events (MACEs, cardiovascular death, nonfatal myocardial infarction, ischemia driven target vessel revascularization) and stent thrombosis (ST) according to the definitions set by the Academic Research Consortium. Propensity score (PS) analysis was performed to adjust different baseline characteristics. The mean follow-up duration was 38 +/- 8 month (at least 36 month and up to 53 month). The 3-year MACE rate did not show a significant difference between the two groups [52 (12.1%) in SES vs. 29 (14.1%) in PES, P = 0.496]. The definite and probable ST at 3 year were similar in both SES and PES [12 (2.8%) in SES vs. 7 (3.4%) in PES, P = 0.681]. There were no differences in hazard ratio for MACE and ST between two stents [MACE, crude: 0.844 (0.536-1.330) and adjusted for PS: 0.858 (0.530-1.389); ST, crude: 0.820 (0.323-2.083) and adjusted for PS: 0.960 (0.357-2.587)]. The present study demonstrated that long-tem cardiac outcomes including ST were not significantly different between SES and PES in patients with DM.


Morphometric study of the guinea pig small intestine during development.
The mucosal surface area of the guinea pig duodenum, jejunum, and ileum was determined during development, in three age groups: 1-day-old and 2- and 12-week-old animals. The morphometric analysis was performed at three magnification levels. The nominal surface area was determined at the macroscopic level, from intestinal length and perimeter. Villus and microvillus amplification factors were estimated at light-microscopic and transmission electron-microscopic levels, respectively. We found: (1) an increase in the nominal surface area that is maximal in the ileum (7.7-fold); (2) an increase in the villus amplification factor in the duodenum (1.4-fold) and a decline in the jejunum and ileum (0.8-fold), although in the jejunum villus dimensions rise; and (3) a similar increase in the microvillus amplification factor in the three segments (1.1- to 1.4-fold). In conclusion, the total mucosal surface area increased from day 1 to week 12, by 3-fold in the duodenum and jejunum and by 8-fold in the ileum. Regionally, the jejunum shows the largest mucosal surface area, followed by the ileum, and, finally, the duodenum.


Characteristics of and Public Health Emergency Responses to COVID-19 and H1N1 Outbreaks: A Case-Comparison Study.
Recently, the novel coronavirus disease (COVID-19) has already spread rapidly as a global pandemic, just like the H1N1 swine influenza in 2009. Evidences have indicated that the efficiency of emergency response was considered crucial to curb the spread of the emerging infectious disease. However, studies of COVID-19 on this topic are relatively few. A qualitative comparative study was conducted to compare the timeline of emergency responses to H1N1 (2009) and COVID-19, by using a set of six key time nodes selected from international literature. Besides, we also explored the spread speed and peak time of COVID-19 and H1N1 swine influenza by comparing the confirmed cases in the same time interval. The government's entire emergency responses to the epidemic, H1N1 swine influenza (2009) completed in 28 days, and COVID-19 (2019) completed in 46 days. Emergency responses speed for H1N1 was 18 days faster. As for the epidemic spread speed, the peak time of H1N1 came about 4 weeks later than that of COVID-19, and the H1N1 curve in America was flatter than COVID-19 in China within the first four months after the disease emerged. The speed of the emergency responses to H1N1 was faster than COVID-19, which might be an important influential factor for slowing down the arrival of the peak time at the beginning of the epidemic. Although COVID-19 in China is coming to an end, the government should improve the public health emergency system, in order to control the spread of the epidemic and lessen the adverse social effects in possible future outbreaks.


[Materno-fetal colonization by group B beta-hemolytic streptococcus and neonatal meningitis].
Two cases of purulent meningitis by Group B streptococci are reported. The bacteria agents were clearly transmitted transplacentally from mother to child. The bacteriological and clinical data are reported and discussed in relation to international literature.


Characterization of Aggregatibacter actinomycetemcomitans strains in periodontitis patients in Germany.
Aggregatibacter actinomycetemcomitans strains of serotype b and with a deletion of 530 bp in the promoter region of the leukotoxin gene (JP2 clone) are known to be associated with severe periodontitis. Our study was aimed to detect virulence genes of A. actinomycetemcomitans strains obtained from patients living in four German cities with different proportions of immigrants. Samples were obtained from severe periodontitis patients in Frankfurt, Hamburg, Leipzig, and Jena. Those being tested positive for A. actinomycetemcomitans were analyzed for serotypes, deletion in the promoter region of the leukotoxin gene, presence of cytolethal distending toxin encoding genes (cdtA, cdtB, and cdtC) and fibril gene1(flp-1). From all 99 A. actinomycetemcomitans-positive samples, the JP2 clone was found in two immigrants in Frankfurt. Seventy strains were tested positive for the cdtA, 52 for cdtB, and 92 for cdtC and flp-1 genes. Twenty-five strains belonged to serotype a, 22 to serotype b, 21 to serotype c, 31 to the others or could not be serotyped, respectively. The distribution of the serotypes differed between the cities. Further, differences regarding the serotypes were also significant between natives and immigrants. The JP2 clone is not spread within the Caucasian inhabitants in German cities. The serotypes distribution seems to be influenced by the numbers of immigrants in the cities. Patients originated from North Africa should be especially screened for the presence of the deletion in the ltx promoter region.


Prospective study of the association between fluoride intake and dental fluorosis in permanent teeth.
To evaluate the relationship between fluoride intake and dental fluorosis in permanent central incisors and first molars. Fluoride intake (mg F/kg body weight/day) from diet, dentifrice and both combined was determined on a single occasion in 1998 among children aged 19-39 months living in two fluoridated Brazilian communities (0.6-0.8 ppm F). Six years later, when the permanent teeth of these children had erupted (central incisors and first molars), 49 children aged 7-9 years [20 girls (40.8%) and 29 boys (58.2%)] were evaluated for dental fluorosis. To test the association between fluorosis and fluoride intake, children were dichotomized into two groups, cases (children with dental fluorosis on at least two teeth, TFI > or =1) and noncases (children without dental fluorosis, TFI = 0). Among the case group (n = 29), median fluoride doses from diet, dentifrice and combined were 0.031, 0.050 and 0.083 mg F/kg/day, respectively. Among the noncase group (n = 20), median fluoride doses were 0.029, 0.049, 0.084 mg F/kg/day, respectively. There was no association between dental fluorosis in permanent teeth and fluoride intake from diet, dentifrice and combined (p > 0.05). There was no difference between children with and without fluorosis in the permanent central incisors and first molars regarding fluoride intake. However, this study has limitations that must be recognized: fluoride intake was only measured once, and there were no children in the sample with severe degrees of dental fluorosis.


Efficacy of plasma exchange and methylprednisolone pulse therapy on influenza-associated encephalopathy.
Patients with a new type of influenza-associated encephalopathy with high mortality are increasing in Japan and the United States. We present three patients treated with methyprednisolone pulse treatment and plasma exchange to remove cytokines, and all three patients recovered without severe sequela. IL-6 decreased dramatically after the start of the plasma exchange and methyprednisolone. Therefore when influenza-associated encephalopathy is actually diagnosed, steroid pulse therapy should be started at an early stage, and when signs of DIC and/or MOF appear, plasma exchange is recommended to remove the cytokines and NOx.


Phosphorylation of myelin basic protein by glycogen phosphorylase kinase.
The ability of homogeneous glycogen phosphorylase kinase (Phk) from rabbit skeletal muscle to phosphorylate bovine brain myelin basic protein (MBP) was investigated. Phk could incorporate a maximum of 1.9 mol phosphate/mol MBP. The apparent Km and Vmax for Phk phosphorylation of MBP were 27 microM and 90 nmol/min per mg enzyme, respectively. Properties of MBP phosphorylation by Phk are similar to those of phosphorylase as a substrate. Only serine residues of MBP are phosphorylated by Phk. Phosphorylation sites of MBP by Phk are not identical to those by cAMP-dependent protein kinases.


On the tryptic peptides from hemoglobin chains of six carnivores.
The amino acid compositions of the tryptic peptides of the following carnivore hemoglobin chains have been determined: gray fox (Urocyon cineroargenteus); raccoon (Procyon lotor); polar bear (Thalarctos maritimus); coati mundi (Nasua nasua) beta chain; coati mundi (Nasua narica) two beta chains; cat (Felis catus) alpha chain; and lion (Pantbera leo) beta chain. These provide a basis for future sequencing of these hemoglobins and construction of an evolutionary tree. The specific results are summarized in the following article (Stenzel and Brimhall, 1977).


Bupivacaine acute toxicity protection by diazepam in mice.
1. The effects of acute and 8-day administration of diazepam (DZP) on the acute toxicity of bupivacaine in the mouse were studied. 2. Protection of bupivacaine-induced acute toxicity by DZP appears to be dose-dependent after treatment for 8 days but not after acute treatment.


Musculoskeletal pain in patients with chronic kidney disease.
Chronic musculoskeletal pain (CMP) is a very common symptom in patients with chronic kidney disease (CKD), and is associated with a significant deterioration in quality of life. To determine the prevalence and clinical characteristics associated with CMP in patients with advanced CKD not on dialysis, and to analyse their relation with other uraemic symptoms and their prognosis significance. Cross-sectional study to analyse the uraemic symptoms of an unselected cohort of patients with CKD stage 4-5 pre-dialysis. In order to characterise patients with CMP, demographic and anthropometric data were collected, as well as data on comorbidities and kidney function. In addition, inflammatory parameters, uric parameters, bone mineral metabolism including 25-hydroxycholecalciferol (25-OHCC), creatine kinase and drugs of potential interest including allopurinol, statins and erythropoiesis-stimulating agents were recorded. The study group consisted of 1169 patients (mean age 65±15 years, 54% male). A total of 38% of patients complained of CMP, and this symptom was more prevalent in women than in men (49 vs. 28%; P<.0001). Muscle weakness, pruritus, muscle cramps, ecchymosis, insomnia, oedema and dyspnoea were the most common symptoms associated with CMP. There were no significant associations between serum levels of creatine kinase, 25-OHCC, treatment with allopurinol, statins or erythropoiesis-stimulating agents and CMP. The female gender, elderly age, obesity, comorbidity (mainly diabetes, heart failure or COPD), and elevated levels of inflammatory markers (C-reactive protein and non-neutrophilic leukocytes) were the best determinants of CMP. While patients with CMP showed a worse survival rate, a multivariate analysis adjusted for demographic data ruled out the independent association of CMP with mortality. CMP is highly prevalent in patients with advanced CKD and is associated with other common symptoms of chronic uraemia. As with the general population, elderly age, the female gender, obesity and some comorbid conditions are the best determinants of CMP. Increased inflammatory markers commonly observed in patients with CMP may have a relevant role in its pathogenesis.


In vitro susceptibility of Ureaplasma urealyticum to rosaramicin.
Thirty-two clinical isolates of Ureaplasma urealyticum were inhibited by 0.036 mug of rosaramicin per ml, whereas 25 (78%) and 13 (41%) of the strains were inhibited by this concentration of minocycline and tetracycline, respectively. These results suggest that rosaramicin may be useful for the treatment of U. urealyticum infections.


Parental Attachment, Self-Esteem, Social Problem-Solving, Intimate Partner Violence Victimization in Emerging Adulthood.
Emerging adults can experience conflicts with their dating partner, leading to intimate partner violence (IPV). In order to understand the vulnerability factors involved in IPV victimization, the current study explored a serial multiple mediation model to determine the links between parental attachment (to the father and mother), self-esteem, and social problem solving (SPS) on the three forms of IPV (psychological, physical and sexual). Based on an online survey, 756 emerging adults (84.8% women, mean age = 23.52) completed self-report questionnaires related to parental attachment, self-esteem, SPS (avoidance and impulsive/carelessness style), and IPV during the past year. The study design was cross-sectional and data were analyzed through partial least structural equation modeling (PLS-SEM) technique. The findings did not support serial multiple mediation model, as the indirect effects of the two specific mediation models were not significant. However, the total indirect effects were significant, indicating a cascade effect chain of events between the variables; insecure parental attachment was related to lower self-esteem, which was associated with poor SPS skills (especially impulsive/carelessness style), which in turn was associated with both psychological and physical violence victimization. The implications of the findings for promoting the life skills of emerging adults, such as problem solving or self-esteem, to enable them to handle their relationship conflicts are discussed.


Zearalenone production in wheat cultivars infected with the fungusFusarium graminearum Schwabe.
In wheat plants of the eultivars "Danubia", "Agra", "Selekta" and "Jubilejna" the fungusFusarium graminsarum Schwabe produced toxic metabolite zearalenone/F-2/ which simultaneously influenced the development of plants characterized by a lower germinating capacity, a reduced growth rate and a higher production of side branches. The presence ofFusarium graminearum was confirmed only in infected plants after plating of organs (root, stem base, stem) and soil on agar medium. The mycotoxin production is dependent on the pathogen development in host plants. The F-2 level progressed from the root into the soil, stem base and stem. The highest F-2 production was identified in cultivar "Selekta" the lowest in cultivar "Danubia". The highest F-2 level (in all wheat eultivars) was identified in the stem base.


Sustained saturating level of glycine induces changes in NR2B-containing-NMDA receptor localization in the CA1 region of the hippocampus.
Post-synaptic actions of glycine are terminated by specialized transporters. There are two genes encoding glycine transporters, GlyT1 and GlyT2. Glycine acts as a co-agonist at N-methyl-d-aspartate glutamatergic receptors (NMDARs). Blockage of GlyT1 enhances NMDAR function by controlling ambient glycine concentrations. Using whole-cell patch-clamp recordings of acute hippocampal slices, we investigated NMDAR kinetics of CA1 pyramidal neurons of mice expressing 50% of GlyT1 (GlyT1+/-). In this study, we report that the glycine modulatory site of the NMDAR at CA1 synapses is saturated in GlyT1+/- but not in wild-type (WT) mice. We also found that the effect of ifenprodil, a highly selective NR2B-containing-NMDAR antagonist, is significantly reduced at CA1 synapses in GlyT1+/- compared to WT mice while immunoblotting experiments do not show significant differences for NR1, NR2A-B-C-D subunits in both types of mice, suggesting alteration in NR2B-containing-NMDAR localization under a state of chronic saturating level of endogenous glycine. Using a pharmacological approach with MK-801 and DL-TBOA, we discriminated synaptic vis-à-vis extra-synaptic NMDARs. We found that NR2B-containing-NMDARs are expressed at a higher level in the extra-synaptic area of CA1 pyramidal neurons from GlyT1+/- compared to WT mice. Our results demonstrate that chronic saturating level of glycine induces significant changes in NMDAR localization and kinetic. Therefore, results from our study should help to gain a better understanding of the role of glycine in pathological conditions.


Genetic diversity analysis of buffalo fatty acid synthase (FASN) gene and its differential expression among bovines.
Fatty Acid Synthase (FASN) gene seems to be structurally and functionally different in bovines in view of their distinctive fatty acid synthesis process. Structural variation and differential expression of FASN gene is reported in buffalo (Bubalus bubalis), a bovine species close to cattle, in this study. Amino acid sequence and phylogenetic analysis of functionally important thioesterase (TE) domain of FASN revealed its conserved nature across mammals. Amino acid residues at TE domain, responsible for substrate binding and processing, were found to be invariant in all the mammalian species. A total of seven polymorphic nucleotide sites, including two in coding region of TE domain were identified across the 10 buffalo populations of riverine and swamp types. G and C alleles were found almost fixed at g18996 and g19056 loci, respectively in riverine buffaloes. Principal component analysis of three SNPs (g18433, g18996 and g19056) revealed distinct classification of riverine and swamp buffalo populations. Reverse Transcription-PCR amplification of mRNA corresponding to exon 8-10 region of buffalo FASN helped in identification of two transcript variants; one transcript of 565 nucleotides and another alternate transcript of 207 nucleotides, seems to have arisen through alternative splicing. Both the transcripts were found to be expressed in most of the vital tissues of buffalo with the highest expression in mammary gland. Semi-quantitative and real-time expression analysis across 13 different buffalo tissues revealed its highest expression in lactating mammary gland. When compared, expression of FASN was also found to be higher in liver, adipose and skeletal muscle of buffalo tissues, than cattle. However, the FASN expression was highest in adipose among the three tissues in both the species. Results indicate structural and functional distinctiveness of bovine FASN. Presence of alternate splicing in buffalo FASN also seems to be a unique phenomenon to the bovines, probably associated with mRNA based regulation of the biological functions of FASN in these species.


Clinical and radiological outcome after anterior cervical discectomy and fusion with stand-alone empty polyetheretherketone (PEEK) cages.
To evaluate long-term results after one-, two-, and three-level anterior cervical discectomy and fusion (ACDF) with stand-alone empty polyetheretherketone (PEEK) cages. We performed a retrospective review of a consecutive patient cohort that underwent ACDF with stand-alone empty PEEK cages between 2007 and 2010 with a minimum follow-up of 12 months. Radiographic follow-up included static and flexion/extension radiographs. Changes in the operated segments were measured and compared to radiographs directly after surgery. Clinical outcome was evaluated by a physical examination, pain visual analog scale (VAS), and health-related quality of life (HRQL) using the EuroQOL questionnaire (EQ-5D). Analysis of associations between fusion, subsidence, cervical alignment, and clinical outcome parameters were performed. Of 407 consecutive cases, 318 met all inclusion criteria. Follow-up data were obtained from 265 (83 %) cases. The mean age at presentation was 55 years and 139 patients were male (52 %). In the sample, 127, 125, and 13 patients had one-, two-, and three-level surgeries, respectively; 132 (49 %) presented with spondylotic cervical myelopathy and 133 (50 %) with cervical radiculopathy. Fusion was achieved in 85, 95, and 94 % of segments in one-, two-, and three-level surgeries, respectively. Non-fusion was associated with higher VAS pain levels. Radiographic adjacent segment disease (ASD) was observed in 20, 29, and 15 % in one-, two-, and three-level surgeries, respectively. ASD was associated with lower HRQL. Subsidence was observed in 25, 27, and 15 % of segments in one-, two-, and three-level surgeries, respectively. However, this had no influence on clinical outcome. Follow-up operations for symptomatic adjacent disc disease and implant failure at index level were needed in 16 (6 %) and four (1.5 %) cases, respectively. Younger age was associated with better clinical outcome. Multilevel surgery favored better myelopathy outcomes and fusion reduced overall pain. ASD worsened EuroQOL-Index values. Worsening of the cervical alignment induced arm pain. One- and two-level ACDF with stand-alone empty PEEK cages achieved very high fusion rates and a low rate of follow-up operations. The rate of good clinical outcome is highly satisfactory. Younger age was the single most influential factor associated with better clinical outcome.


Parasite clearance, cure rate, post-treatment prophylaxis and safety of standard 3-day versus an extended 6-day treatment of artemether-lumefantrine and a single low-dose primaquine for uncomplicated Plasmodium falciparum malaria in Bagamoyo district, Tanzania: a randomized controlled trial.
Artemisinin-based combination therapy (ACT) resistant Plasmodium falciparum represents an increasing threat to Africa. Extended ACT regimens from standard 3 to 6 days may represent a means to prevent its development and potential spread in Africa. Standard 3-day treatment with artemether-lumefantrine (control) was compared to extended 6-day treatment and single low-dose primaquine (intervention); in a randomized controlled, parallel group, superiority clinical trial of patients aged 1-65 years with microscopy confirmed uncomplicated P. falciparum malaria, enrolled in Bagamoyo district, Tanzania. The study evaluated parasite clearance, including proportion of PCR detectable P. falciparum on days 5 and 7 (primary endpoint), cure rate, post-treatment prophylaxis, safety and tolerability. Clinical, and laboratory assessments, including ECG were conducted during 42 days of follow-up. Blood samples were collected for parasite detection (by microscopy and PCR), molecular genotyping and pharmacokinetic analyses. Kaplan-Meier survival analyses were done for both parasite clearance and recurrence. A total of 280 patients were enrolled, 141 and 139 in the control and intervention arm, respectively, of whom 121 completed 42 days follow-up in each arm. There was no difference in proportion of PCR positivity across the arms at day 5 (80/130 (61.5%) vs 89/134 (66.4%), p = 0.44), or day 7 (71/129 (55.0%) vs 70/134 (52.2%), p = 0.71). Day 42 microscopy determined cure rates (PCR adjusted) were 97.4% (100/103) and 98.3% (110/112), p = 0.65, in the control and intervention arm, respectively. Microscopy determined crude recurrent parasitaemia during follow-up was 21/121 (17.4%) in the control and 14/121 (11.6%) in the intervention arm, p = 0.20, and it took 34 days and 42 days in the respective arms for 90% of the patients to remain without recurrent parasitaemia. Lumefantrine exposure was significantly higher in intervention arm from D3 to D42, but cardiac, biochemical and haematological safety was high and similar in both arms. Extended 6-day artemether-lumefantrine treatment and a single low-dose of primaquine was not superior to standard 3-day treatment for ACT sensitive P. falciparum infections but, importantly, equally efficacious and safe. Thus, extended artemether-lumefantrine treatment may be considered as a future treatment regimen for ACT resistant P. falciparum, to prolong the therapeutic lifespan of ACT in Africa. Trial registration ClinicalTrials.gov, NCT03241901. Registered July 27, 2017 https://clinicaltrials.gov/show/NCT03241901.


[Oxytocin and maternal stress during the post-partum period].
Oxytocin is required for lactation by promoting milk expulsion. Oxytocin has also been reported to exert a positive role in social attachment. The postpartum period has been shown to be crucial for maternal behavior initiation, and required self-trust reinforcement. However, this period is also remarkable for the high risk exposure of either psychic or physical stress. A negative impact on young mother is suspected, both in the short, medium or long term, which can even be deleterious for child-mother relationships. During lactation in female rats and sheep, oxytocin production has been proved to decrease stress-induced hormonal changes and later consequences. In human beings, only the first hour after breast-feeding seems to protect against physical or psychic stress. Oxytocin improves the stress-induced response by reducing the ACTH and cortisol secretion thus representing a potential therapeutic pathway in post-partum pathologies such as depression. Thus, this review of recent literature about oxytocin and stress during post-partum period, leads to the assumption that oxytocin, at the moment of installation of breastfeeding, acts not only on the physiological condition, but also on the psychic condition of the mother.


Glycemic control and BMI changes after endoscopic implantation of a duodenojejunal bypass liner compared with laparoscopic Roux-en-Y gastric bypass surgery: a propensity score matching analysis.
Both laparoscopic Roux-en-Y gastric bypass (RYGB) and duodenojejunal bypass liner (DJBL) have been shown to induce weight loss and dramatically ameliorate type 2 diabetes mellitus (T2DM). Since DJBL implantation causes nutrients to pass through the duodenum without contact with the digestive juices and the duodenal mucosa, its mechanisms have been suggested to mimic those of RYGB. This study aimed to compare the outcomes of these two bariatric procedures in terms of glycemic control and BMI in patients with obesity and T2DM. A retrospective observational cohort propensity score-weighted comparison of laparoscopic Roux-en-Y gastric bypass (RYGB) vs duodenojejunal bypass liner (DJBL) was conducted in patients with obesity and T2DM undergoing either procedure from 05/2014 to 12/2017. Propensity scores were weighted for body weight, body mass index (BMI), and glycated hemoglobin A1c (HbA1c). The primary outcome was comparative improvement of HbA1c. Secondary comparative effectiveness outcomes were decrease of body weight and BMI. Forty-six patients were included: 21 (10 male, 11 female; mean age 50.6 ± 11.7 years) underwent RYGB, while DJBL was implanted in 25 (10 male, 15 female; 52.5 ± 9.5 years). After twelve months, mean ΔBMI was 11.54 ± 4.47 kg/m2 for RYGB vs. 6.23 ± 2.36 kg/m2 for DJBL (p < 0.05). Mean total weight loss was 27.93 ± 8.57% for RYGB vs. 15.04 ± 5.73% for DJBL (p < 0.05). Glycemic control after one year improved significantly in both groups but did not differ significantly. RYGB and DJBL seem to be associated with similar remission rates of hyperglycemia after one year. However, RYGB induces more significant weight loss than DJBL.


Bridging the gap between constrained spherical deconvolution and diffusional variance decomposition via tensor-valued diffusion MRI.
Diffusion tensor imaging (DTI) is widely used to extract valuable tissue measurements and white matter (WM) fiber orientations, even though its lack of specificity is now well-known, especially for WM fiber crossings. Models such as constrained spherical deconvolution (CSD) take advantage of high angular resolution diffusion imaging (HARDI) data to compute fiber orientation distribution functions (fODF) and tackle the orientational part of the DTI limitations. Furthermore, the recent introduction of tensor-valued diffusion MRI allows for diffusional variance decomposition (DIVIDE), enabling the computation of measures more specific to microstructure than DTI measures, such as microscopic fractional anisotropy (μFA). Recent work on making CSD compatible with tensor-valued diffusion MRI data opens the door for methods combining CSD and DIVIDE to get both fODFs and microstructure measures. However, the impacts of such atypical data on fODF reconstruction with CSD are yet to be fully known and understood. In this work, we use simulated data to explore the effects of various combinations of diffusion encodings on the angular resolution of extracted fOFDs and on the versatility of CSD in multiple realistic situations. We also compare the combinations with regards to their performance at producing accurate and precise μFA with DIVIDE, and present an optimized 10 min protocol combining linear and spherical b-tensor encodings for both methods. We show that our proposed protocol enables the reconstruction of both fODFs and μFA on in vivo data.


Role of Toluidine Blue Staining in Suspicious Lesions of Oral Cavity and Oropharynx.
Oral cancer; the sixth most common malignancy in the world has one of the lowest 5 year survival rates. This can be attributed mainly to the delay in diagnosis. The purpose of this study was to evaluate the efficacy of vital staining with toluidine blue dye as an adjunct to standard clinical examination to facilitate early detection of malignant lesions of oral cavity and oropharynx. A hospital based diagnostic test accuracy study was carried out on 55 subjects with oral mucosal disorders that included clinically suspicious premalignant or malignant lesions, in the Department of ENT, Academy of Medical Sciences, Pariyaram, Kannur, Kerala over a period of 2 years. All lesions were subjected to detailed clinical examination and toluidine blue staining; and dye retention was recorded with photographs. The results of staining were compared with findings on histopathological examination. The Sensitivity and specificity of toluidine blue test for the detection of malignancy was 92.6 and 67.9% respectively; and the overall diagnostic accuracy was 80%. The result was highly significant with a 'p value' <0.001. The results indicate that toluidine blue staining is a simple, non-invasive technique which can be a valuable adjunct in the diagnostic process of oral and oropharyngeal cancers.


Influence of sarcosine or N-methylalanine in position 7 on the antagonistic properties of [1-deaminopenicillamine]- and [1-(beta-mercapto-beta, beta-cyclopentylmethylene-propionic acid)]-vasopressin.
Substituting sarcosine or N-methylalanine for proline in the inhibitory vasopressin analogs dPAVP and d(CH2)5AVP had the following effects: 1) milk ejection and antidiuretic activities were severely depressed, 2) pressor antagonism was maintained but weakened somewhat, and 3) antagonism in the uterus in vitro was maintained, but no consistent pattern was seen.


Unraveling the joint toxicity of transition-metal dichalcogenides and per- and polyfluoroalkyl substances in aqueous mediums by experimentation, machine learning and molecular dynamics.
The environmental fate of transition-metal dichalcogenides (TMDCs) may be further complicated by interacting with existing pollutants, especially per- and polyfluoroalkyl substances (PFAS). However, due to their sheer volume, it is impossible to explore all possible interactions by simply utilizing experimental methods. Herein, we used two model TMDC nanosheets, molybdenum disulfide (MoS2) and tungsten disulfide (WS2), and seven PFAS to explore their interactions and subsequent impacts on model cell lines and zebrafish. Utilizing experimental methods and machine learning approaches, we showed that TMDCs-PFAS interactions can pose unique challenges due to their interaction-specific toxicity niches towards cell lines. Further in vivo experiments, together with molecular dynamics simulation, suggested that TMDCs-PFAS interactions in aqueous environments significantly increased their bioaccumulation in zebrafish towards different target organs, mostly due to the differences in loading PFAS. Such enhanced bioaccumulation increased the oxidative stress in zebrafish liver and intestine, as demonstrated by the increased reactive oxygen species (ROS) level and other enzyme activities, which eventually led to obvious histopathological alterations in the liver and intestine. Our study highlights the importance of exploring interactions between emerging and existing contaminants with state-of-art techniques in aqueous environments and its significance in safeguarding aquatic environment health.


Human Breast Milk-Derived Extracellular Vesicles in the Protection Against Experimental Necrotizing Enterocolitis.
Necrotizing enterocolitis (NEC) is a leading cause of death in premature infants. Breast feeding decreases the incidence of NEC but, even with aggressive promotion of nursing in Neonatal Intensive Care Units, morbidity and mortality remain high. Previous studies from our laboratory have demonstrated that extracellular vesicles (EVs) purified from mouse and rat stem cells can protect the intestines from NEC. The aim of this study was to determine whether human breast milk (BM)-derived EVs could prevent NEC. EVs were purified from human donor breast milk. NEC was induced in premature rat pups by exposure to asphyxia/hypothermia/hypercaloric feeds. Pups were randomized to: (1) breast fed, no injury, (2) NEC, (3) NEC + BM-derived EVs once intraperitoneally (IP), (4) NEC + BM-derived EVs enterally (PO) with each feed. Intestinal tracts were examined for histologic damage. Additionally, the effect of BM-derived EVs on intestinal epithelial cells (IEC) subjected to hypoxia/reoxygenation injury in vitro was examined. NEC incidence was 0% in breast-fed pups and 62% in pups subjected to NEC. IP administration of BM-derived EVs decreased NEC incidence to 29% and enteral administration further decreased NEC incidence to 11.9%. (p < 0.05). BM-derived EVs significantly increased cell proliferation and decreased apoptosis in IEC in vitro. Breast milk-derived EVs delivered either IP or enterally significantly decrease the incidence and severity of experimental NEC, protect IEC from injury in vitro, and may represent an innovative therapeutic option for NEC in the future. Basic science study. N/A.


Computational fluid dynamics and factor analysis of a novel swirling demulsified airlift loop reactor for the treatment of refined soybean oil wastewater.
A swirling demulsified airlift loop reactor (SD-ALR) was developed for the treatment of oily wastewater with yeasts. Computational fluid dynamics simulations showed that the gas holdup and liquid velocity gradient in the SD-ALR were 2.9% and 0.37 m/s higher than those in the traditional airlift loop reactor. The optimization results of the swirling demulsifier showed that the optimal number and elevation angle of the blades were 8 and 45°, and the optimal installation position was 150 mm from the bottom of the draft tube. The results of treating refined soybean oil wastewater in the SD-ALR showed that the wastewater treatment time was decreased by 8 h, and the removals of chemical oxygen demand and oil content increased by 5.10% ± 0.02% and 9.55% ± 0.40%, respectively, compared with those in the traditional airlift loop reactor. A volumetric mass transfer coefficient model was established for SD-ALR and oily wastewater.


Application of a new percutaneous multi-function pedicle locator in minimally invasive spine surgery.
In this study, a new percutaneous multi-function pedicle locator was designed for personalized three-dimensional positioning of a pedicle in minimally invasive spine surgery (MISS) without computer-assisted navigation technology. The proposed locator was used in a number of patients during MISS, and its advantages were analyzed. Based on the position of a pedicle determined by computed tomography (CT) and fluoroscopic images of a patient, 6 lines and 2 distances were used to determine the puncture point of a pedicle screw on skin, while 2 angles were used to indicate the direction of insertion of a pedicle guide needle from the patient's body surface. The results of the proposed locator were compared with those of the conventional freehand technique in MISS. The potential benefits of using the locator included enhanced surgical accuracy, reduced operation time, alleviation of the harmful intra-operative radiation exposure, lower costs, and shortened learning curve for young orthopedists.


Theoretical investigations on the interactions of glucokinase regulatory protein with fructose phosphates.
Glucokinase (GK) plays a critical role in maintaining glucose homeostasis in the human liver and pancreas. In the liver, the activity of GK is modulated by the glucokinase regulatory protein (GKRP) which functions as a competitive inhibitor of glucose to bind to GK. Moreover, the inhibitory intensity of GKRP-GK is suppressed by fructose 1-phosphate (F1P), and reinforced by fructose 6-phosphate (F6P). Here, we employed a series of computational techniques to explore the interactions of fructose phosphates with GKRP. Calculation results reveal that F1P and F6P can bind to the same active site of GKRP with different binding modes, and electrostatic interaction provides a major driving force for the ligand binding. The presence of fructose phosphate severely influences the motions of protein and the conformational space, and the structural change of sugar phosphate influences its interactions with GKRP, leading to a large conformational rearrangement of loop2 in the SIS2 domain. In particular, the binding of F6P to GKRP facilitates the protruding loop2 contacting with GK to form the stable GK-GKRP complex. The conserved residues 179-184 of GKRP play a major role in the binding of phosphate group and maintaining the stability of GKRP. These results may provide deep insight into the regulatory mechanism of GKRP to the activity of GK.


Serum beta human chorionic gonadotropin levels at 16 days following embryo transfer in intra cytoplasmic sperm injection cycles to predict pregnancy outcome.
To determine the prognostic value of beta human chorionic gonadotropin (B-hCG) concentration on the sixteenth day after embryo transfer to predict pregnancy outcome. In this retrospective cohort study, B-hCG levels were measured in 97 pregnant women that underwent intra-cytoplasmic sperm injection (ICSI) in Fatemeh-Zahra Infertility and Reproductive Health Research Center, Babol University of Medical Sciences, Babol, Iran from January 2008 to December 2009. Type, duration, causes of infertility, and age of patients, B-hCG levels on the sixteenth day after embryo transfer, the number of embryos, and pregnancy outcome were assessed. Incidence of viable pregnancies in B-hCG levels less than 100 IU/L (n=18) was 38.9%, and in B-hCG levels more than or equal to 100 IU/L (n=79) was 84.4%. Correlation of B-hCG with pregnancy outcome was significant (p less than 0.001). Cut-off value of B-hCG to predict viable pregnancy was 100 IU/L (sensitivity - 91%, specificity - 48%, PPV - 85%, and NPV - 61%). The B-hCG levels less than or equal to 200 IU/L with a sensitivity of 88%, specificity of 45%, PPV - 37%, and NPV = 91% had predicted twin pregnancy. Serum B-hCG level on the sixteenth day after embryo transfer can be useful to predict the pregnancy outcome in ICSI cycles.


Establishing Fascin over-expression as a strategic regulator of neoplastic aggression and lymph node metastasis in oral squamous cell carcinoma tumor microenvironment.
Oral squamous cell carcinoma (OSCC) has an aggressive behaviour with high incidence of nodal metastasis, even in the early stages, leading to poor prognosis. For progression and metastasis of cancers, the dominant element considered is cell motility. Fascin, an actin-binding protein has emerged as a protein of general importance for a diverse set of cell protrusions with functions in cell adhesion, cell interactions, and cell migration. The role of Fascin in various carcinomas, including aggressive behaviour in OSCC has been documented, but its role as a key regulator in lymph nodes metastasis is yet to be validated. This study was piloted to evaluate and correlate Fascin expression in OSCC lymph nodes and understand the role of Fascin in contemptuous Lesional tissue, as a predictor of survival. A retrospective study designed with 40 archival OSCC cases was included as sample, 20 each of both lymph node metastasis +ve (Group 1) and -ve (Group 2) groups. All the participants were smokeless tobacco user and had tumor located at gingivo-buccal complex. We established that Fascin over-expression in lymph nodes were significantly associated with clinico-histopathological parameters like staging (p=0.01), tumor size (cT) (p=0.03) and differentiation; and furthermore it was highly significant in correlation to nodal status (cN) (*p≤0.001). Fascin over-expression in lymph node metastasis positive cases correlated with that of Fascin expression in contemptuous Lesional tissue signifying its role in promoting aggressive progression and metastasis. This association was found to be statistically significant (p value=0.05). Overall Survival Analysis of both lymph node metastasis +ve and -ve groups assessed by Kaplan-Meier analysis (taking death and recurrence into consideration) showed patients with high Fascin expression (in lymph node and Lesional tissue) had shorter overall survival than patients who had no to weak Fascin expression. Our findings thereby establish Fascin expression as a regulator of metastasis in OSCC tumor microenvironment and predictor of survival.


Characteristics of the Residential Environment and Their Association With Depression in Hong Kong.
With rapid urbanization, understanding the role of residential environments in the development of depression has gained importance. However, the potential associations of residential space and density with depression have been understudied. To investigate longitudinal associations of residential livable space and density with depression. This longitudinal cohort study used data from 2 waves of the FAMILY Cohort, a population-based cohort in the Hong Kong Special Administrative Region, China, recruited between February 28, 2009, and March 28, 2011, at baseline and followed up between August 3, 2011, and June 19, 2013, at wave 2. Data were analyzed from September 1, 2020, through August 10, 2021. A total of 16 968 participants aged 16 years or older underwent assessment using the Patient Health Questionnaire-9 (PHQ-9) and had complete data across all variables. Residential density was objectively assessed at 3 scales (within apartment, building block, and at neighborhood level) at baseline and follow-up. Depressive symptoms were defined in terms of a PHQ-9 threshold greater than or equal to 5 and probable major depression with a cutoff value greater than or equal to 10. A continuous PHQ-9 score was used as a secondary outcome. Multilevel logistic regression models were used to examine associations of the residential density with probable major depression and depressive symptoms adjusted for time-varying sociodemographic and lifestyle factors, comorbidities, and other environment variables. Of the 16 968 participants with complete data, the mean (SD) age was 45.5 (16.7) years, and 9328 participants (55.0%) were women at baseline. The mean follow-up was 2.2 years (range, 1.3-3.6 years). At the household level, after full adjustments, each IQR increment in residential livable area was associated with lower odds of probable major depression (adjusted odds ratio [aOR], 0.84; 95% CI, 0.71-0.98; P = .03) and depressive symptoms (aOR, 0.93; 95% CI, 0.86-1.00; P = .04). At the building-block level, each IQR increment in block density was associated with higher odds of depressive symptoms (aOR, 1.11; 95% CI, 1.01-1.22; P = .03), but only in single-housing environment models. The results remained consistent in models with continuous PHQ-9 evaluation. This study's findings suggest that residential livable space and block density may play a role in the development of depression. Integrated mental health and housing policies promoting mental capital in cities, such as health-optimized density at the household and building-block levels, might serve as a population approach to reduce the burden of depression.


Enkephalins presynaptically inhibit cholinergic transmission in sympathetic ganglia.
Recent biochemical and immunohistochemical studies have shown that the opioid peptides, enkephalins, occur in nerve terminals and cell bodies in mammalian sympathetic ganglia1-3. Opiates and enkephalins are thought to inhibit synaptic transmission in the peripheral nervous tissues as well as in the central nervous system4-12. The mechanisms of the opiate actions, however, are not entirely clear; both pre- and postsynaptic sites of action have been proposed7-9,11,12. As acetylcholine is known to be the major neurotransmitter in the autonomic ganglia and as the mechanism of synaptic transmission is well clarified13, analysis of the peptide action could be more easily but equally usefully carried out in the peripheral synapses than in central synapses. We now report that enkephalins presynaptically inhibit cholinergic transmission in sympathetic ganglia.


Flavor enhancement during the drying of scallop (Patinopecten yessoensis) as revealed by integrated metabolomic and lipidomic analysis.
Dried scallops are a typical shellfish commodity, but the molecular change mechanism in the drying process is not clear. In this paper, the effect of drying on the flavor of scallops was revealed by integrated metabolomic and lipidomic analysis. The results showed that 70 °C was the best temperature for hot air drying, and the moisture content of the scallops was less than 20% after 12 h of drying, which meets the commercial standards for dried scallops. A total of 53 volatile compounds were detected in dried scallops, of which 2,5-dimethyl pyrazine and tetramethyl pyrazine, as characteristic flavor compounds, changed significantly during drying. In addition, taste peptides such as Arg-Gly and Gly-Gly, produced by protein degradation during drying, may contribute to the umami perception of dried scallops. This study helped to increase the overall quality of dried scallops.


FRET Microscopy for Real-Time Visualization of Second Messengers in Living Cells.
Förster Resonance Energy Transfer (FRET) microscopy is a useful tool in molecular biology and medical research to monitor and quantify real-time dynamics of protein-protein interactions and biochemical processes. Using this well-established technique, many novel signaling mechanisms can be investigated in intact cells or tissues and even in various subcellular compartments. Here, we describe how to perform FRET measurements in living cells expressing FRET-based biosensors and how to evaluate these data. This general protocol can be applied for FRET measurements with various fluorescent biosensors.


[CEA (carcinoembryonic antigen): its value as an early indicator of recurrence of neoplastic disease in carcinoma of the colon and rectum].
A personal series is examined in order to assess the reliability of CEA in the diagnosis of returning colorectal cancer and to compare the data accumulated with reports in the literature with a view to establishing reliable criteria for the use and assessment of this test.


Serological evidence of Rift Valley fever in domestic ruminants in Tunisia underlines the need for effective surveillance.
Rift Valley fever (RVF) is an infectious zoonotic disease infecting, mainly, domestic ruminants and causing significant economic and public health problems. RVF is a vector-borne disease transmitted by mosquitoes. In this work, we tried to seek any RVF virus circulation in Tunisia. Thus, we investigated 1,723 sera from different parts of Tunisia, collected in 2009 and 2013-2015 from sheep, goats, cattle, and dromedaries. All sera were assessed using enzyme-linked immunosorbent assay techniques. Eighty-seven sera were detected positive and 11 doubtful. All of them were investigated by the virus-neutralization technique (VNT), which confirmed the positivity of three sera. This is the first case of RVF seropositive confirmed by the VNT in Tunisian ruminants. Such a result was expected considering the climate, entomology, and geographic location of the country. Further investigations must enhance our findings to understand the RVF epidemiologic situation better and implement risk-based surveillance programs and effective control strategies.


A fundamental frequency investigation of children ages 6-10 years old.
The fundamental frequency characteristics of 30 children between the ages of 6 and 10 years were investigated in a variety of speech tasks. The results indicated that average fundamental frequency across tasks for the boys is approximately 262 Hz, and for girls approximately 281 Hz. Statistical analysis indicated that there was no significant difference in the fundamental frequency of boys and girls in this age range. High vowels were found to have higher fundamental frequency values than low vowels. Sustained vowels had higher fundamental frequency values than either spontaneous speech or reading for both groups of speakers. The results of this investigation are discussed in terms of maturational processes, and in comparison to corresponding adult information.


The use of the fish cell lines RTG-2 and PLHC-1 to compare the toxic effects produced by microcystins LR and RR.
Cyanobacterial toxins, especially microcystins (MC), are found in eutrophied waters through the world. Acute poisonings of animals and humans has been reported following MC exposure. In the present study, two fish cell lines, PLHC-1 and RTG-2, were evaluated after exposure to the cyanobacterial toxins MC-LR and MC-RR. The effects of different concentrations of the toxins were investigated in both cell lines at morphological and biochemical levels (total protein content, lactate dehydrogenase leakage, lysosomal activity and succinate dehydrogenase activity). The results obtained showed a decrease in protein content and no relevant increase in cell disruption, except for MC-LR in PLHC-1 cells. Morphological changes produced by microcystins were cellular swelling, blebbling, rounding, reduction in the cell number and increase in the number and size of lysosomal bodies. In addition, steatosis was produced in hepatoma PLHC-1 cells, particularly with MC-RR. Furthermore, the fish PLHC-1 cell line was more sensitive than RTG-2 cells to the cyanobacterial toxins compared, being the stimulation of the lysosomal function and the induction of steatosis the most specific changes detected.


Cancer cells co-opt nociceptive nerves to thrive in nutrient-poor environments and upon nutrient-starvation therapies.
Although nutrient-starvation therapies can elicit strong anti-tumor effects in multiple carcinomas, it has been convincingly demonstrated that cancer cells exploit the tumor microenvironment to thrive in nutrient-poor environments. Here, we reveal that cancer cells can co-opt nociceptive nerves to thrive in nutrient-poor environments. Initially examining the low-glucose environment of oral mucosa carcinomas, we discovered that cancer cells employ ROS-triggered activation of c-Jun to secrete nerve growth factor (NGF), which conditions nociceptive nerves for calcitonin gene-related peptide (CGRP) production. The neurogenic CGRP subsequently induces cytoprotective autophagy in cancer cells through Rap1-mediated disruption of the mTOR-Raptor interaction. Both anti-glycolysis and anti-angiogenesis-based nutrient-starvation therapies aggravate the vicious cycle of cancer cells and nociceptive nerves and therapeutically benefit from blocking neurogenic CGRP with an FDA-approved antimigraine drug. Our study sheds light on the role of the nociceptive nerve as a microenvironmental accomplice of cancer progression in nutrient-poor environments and upon nutrient-starvation therapies.


Bone metastases from breast carcinoma: histopathological - radiological correlations and prognostic features.
The aim of this study was to identify factors that may be associated with the development of bone metastases in patients with metastatic breast carcinoma and to see if any of these factors had a bearing on subsequent survival. In total, 492 patients presented to the Nottingham City Hospital with metastatic breast carcinoma between July 1997 and December 2001. Of these, 267 patients had bone metastases at presentation with metastatic disease, 91 patients in this group had bone as their only site of metastatic disease. Sites of first presentation of metastatic disease were prospectively recorded, as were histological features of the primary tumour (tumour type, histological grade, lymph node stage, tumour size and oestrogen receptor (ER) status). The radiological features of the bone metastases, the metastasis-free interval and serological tumour marker levels at presentation with metastases were all recorded. There was a significant association between the development of bone metastases and lower grade tumours (P=0.019), ER-positive tumours (P<0.0001) and the lymph node stage of the primary tumour (P=0.047). A multivariate analysis found that metastasis-free interval, additional sites of metastatic disease other than bone, ER status and serological tumour marker levels all independently contributed to survival from time of presentation with bone metastases.


Enantioselective Nucleophilic Vinylic Substitution (SNV) toward 3-Alkenyl-bisoxindoles Facilitated by C6' Steric Bulk of Cinchona Alkaloid.
A C6' bulky substituted quinine-catalyzed SNV reaction between 3-substituted oxindole and (E)-3-(nitromethylene)-oxindole was developed. This enantioselective C(sp3)-C(sp2) coupling furnished bisoxindole scaffolds featuring a vinyl-substituted all-carbon quaternary stereocenter with high stereoselectivities. In addition, the gram-scale synthesis and synthetic post-transformations were conducted to demonstrate the potential synthetic usefulness.


Lymphatic transport in patients with chronic venous insufficiency and venous leg ulcers following sequential pneumatic compression.
Recent advancements in near-infrared fluorescence lymphatic imaging (NIRFLI) technology provide opportunities for non-invasive, real-time assessment of lymphatic contribution in the etiology and treatment of ulcers. The objective of this study was to assess lymphatics in subjects with venous leg ulcers using NIRFLI and to assess lymphatic impact of a single session of sequential pneumatic compression (SPC). Following intradermal microdoses of indocyanine green (ICG) as a lymphatic contrast agent, NIRFLI was used in a pilot study to image the lymphatics of 12 subjects with active venous leg ulcers (Clinical, Etiologic, Anatomic, and Pathophysiologic [CEAP] C6). The lymphatics were imaged before and after a single session of SPC to assess impact on lymphatic function. Baseline imaging showed impaired lymphatic function and bilateral dermal backflow in all subjects with chronic venous insufficiency, even those without ulcer formation in the contralateral limb (C0 and C4 disease). SPC therapy caused proximal movement of ICG away from the active wound in 9 of 12 subjects, as indicated by newly recruited functional lymphatic vessels, emptying of distal lymphatic vessels, or proximal movement of extravascular fluid. Subjects with the longest duration of active ulcers had few visible lymphatic vessels, and proximal movement of ICG was not detected after SPC therapy. This study provides visible confirmation of lymphatic dysfunction at an early stage in the etiology of venous ulcer formation and demonstrates the potential therapeutic mechanism of SPC therapy in removing excess fluid. The ability of SPC therapy to restore fluid balance through proximal movement of lymph and interstitial fluid may explain its value in hastening venous ulcer healing. Anatomical differences between the lymphatics of longstanding and more recent venous ulcers may have important therapeutic implications.


The slow step of folding of Staphylococcus aureus PC1 beta-lactamase involves the collapse of a surface loop rate limited by the trans to cis isomerization of a non-proline peptide bond.
We wished to test the hypothesis that the non proline cis to trans isomerization of the peptide bond at position 167 in the S. aureus beta-lactamase PC1 exerts a significant controlling effect on the folding pathway of this enzyme. The previous data presented in support of this hypothesis could not rule out the effect of factors unrelated to non-proline cis/trans isomerization. We have used the plasmid pET9d to direct soluble overproduction of the S. aureus beta-lactamase PC1 and a site-directed mutant (Ile 167 to Pro) in Escherichia coli. Following purification the proteins were subjected to a comparative analysis of the kinetics of unfolding and refolding using the techniques of near- and far-UV circular dichroism spectroscopy and fluorescence spectroscopy in conjunction with "double-jump" experiments. Results show that the fully-unfolded I167P mutant enzyme retains 20% of molecules in a fast-refolding form and that slower-refolding molecules fold faster than the recombinant wild-type enzyme. The final stage of folding involves folding of the omega-loop into a conformation essential for enzymatic activity. In support of the original hypothesis, the folding of this omega-loop is rate limited by the isomerization of the Glu 166-Ile 167 peptide bond.


Anorectal abnormalities in progressive systemic sclerosis.
Seventeen patients with progressive systemic sclerosis (PSS) were evaluated with manometry for anorectal function, and an additional 36 age-matched normal subjects were collected as a control group. The study group had a significant decrement of maximum basal pressure (MBP), 42.6 +/- 27.0 mm Hg, in PSS as compared with the control group, 71.2 +/- 24.9 mm Hg (P = .0004). The difference in the functional length (FL) of the anal canal, PSS:control = 2.4 +/- 1.0 cm:3.7 +/- 0.5 cm (P = .0001); the volume of first defecating sensation, PSS:control = 66.3 +/- 35.2 ml:125.1 +/- 43.8 ml; the voluntary component, the difference between maximum squeeze pressure (MSP) and MBP, PSS:control = 116.6 +/- 73.6 mm Hg:61.8 +/- 35.9 mm Hg (P = .0087), were also found to be statistically significant. Nevertheless, the MSP and maximal tolerable capacity (Vmax) showed no difference in these two groups (MSP, PSS:control = 159.3 +/- 88.1 mm Hg:132.9 +/- 44.9 mm Hg, P = .259), (Vmax, PSS:control = 193.1 +/- 67.7 ml:230.0 +/- 60.9 ml, P = .0526). Twelve (71 percent) of 17 patients did not have rectoanal inhibitory reflex, and paradoxical contraction during rectal balloon inflation was noted in ten patients. Nine patients had different degrees of anal incontinence and abnormal anometric profiles were found in six of eight asymptomatic patients. Therefore, only two patients (12 percent) had neither symptoms nor anometric evidence of anorectal involvement in PSS. Two patients with long-standing disease received posterior anal repair for stool incontinence, the postoperative results were satisfactory both subjectively and objectively. The average MBP increased from 0 to 20 mm Hg, average FL from 0 to 1.5 cm. Patients complained less frequently about stool incontinence or soiling, and their daily life is now more comfortable. The analysis indicates that anorectal function in PSS is affected much more frequently and earlier than thought. Anorectal manometry can be used as an adjuvant in diagnosing controversial cases. Once anal incontinence occurs, posterior anal repair can achieve good results after six months of follow-up.


Time domains of neuronal Ca2+ signaling and associative memory: steps through a calexcitin, ryanodine receptor, K+ channel cascade.
Synaptic changes that underlie associative learning and memory begin with temporally related activity of two or more independent synaptic inputs to common postsynaptic targets. In turn, temporally related molecular events regulate cytosolic Ca2+ during progressively longer-lasting time domains. Associative learning behaviors of living animals have been correlated with changes of neuronal voltage-dependent K+ currents, protein kinase C-mediated phosphorylation and synthesis of the Ca2+ and GTP-binding protein, calexcitin (CE),and increased expression of the Ca2+-releasing ryanodine receptor (type II). These molecular events, some of which have been found to be dysfunctional in Alzheimer's disease, provide means of altering dendritic excitability and thus synaptic efficacy during induction, consolidation and storage of associative memory. Apparently, such stages of behavioral learning correspond to sequential differences of Ca2+ signaling that could occur in spatially segregated dendritic compartments distributed across brain structures, such as the hippocampus.


An accessory thyroid gland that presented tumor-like images.
A 26-year-old woman presented with right breast pain and itching. Incidentally, a firm, non-tender, movable mass (3 cm in diameter) located in the lower right part of the neck was identified by palpation. Ultrasonography revealed a clearly demarcated dumbbell-shaped mass with homogenous hypo- (cranial side) and hyper-echogenicity (caudal side) compared with the thyroid gland. Computed tomography scan and magnetic resonance imaging presented images that were different from thyroid gland substance. The right thyroid lobe was strongly compressed by the mass. Hyperparathyroidism was ruled out by laboratory testing. The patient solicited resection of the mass despite recommendations for core needle biopsy, and it was removed surgically. The mass was surrounded by a thin capsule and was not connected with the thyroid gland. Pathological examinations revealed normal thyroid gland tissue. The final diagnosis was an accessory thyroid gland. Accessory thyroid glands should be considered as a possible diagnosis when nodules around the main thyroid gland are encountered.


Results of a clinical trial of sodium hyaluronate in lens implantation surgery.
The results from a four-year clinical trial on the use of sodium hyaluronate (Healon) are presented. Six hundred three consecutive primary lens implantations were performed: 500 after extracapsular cataract extraction and 103 after intracapsular cataract extraction. The safety and efficacy of Healon were analyzed by examining postoperative ocular hypertension, uveitis, visual acuity, and endothelial cell loss. The results of the trial confirm that Healon is safe and effective and, provided it is not used in excessive quantities, free from serious side effects.


Equine alpha-fetoprotein levels in Lipizzaner mares with normal pregnancies and with pregnancy loss.
Alpha-fetoprotein has proved to be a good indicator of fetal well-being in human medicine for decades. Although this molecule is present in most of the mammalian species including horses, reference values in healthy and high-risk pregnant mares have not yet been published. The aim of the present study was to determine whether equine alpha-fetoprotein (eqAFP) is a good indicator of complicated pregnancies in Lipizzaner mares. A total of 111 serum samples from 30 mares have been analyzed for eqAFP levels throughout gestation (Days 60-325). After the pregnancy was confirmed, 23 mares had normal pregnancies with viable foals, six had late embryonic loss, and one of the mares aborted in the ninth gestational month. Equine alpha-fetoprotein concentrations significantly differed in the normal group (72.93 ± 49.25 pg/mL; mean ± standard deviation) and in the complicated pregnancy loss group (152 ± 36.48 pg/mL; mean ± standard deviation). The mares' age, gestational age, and the conception rate significantly affected the alpha-fetoprotein concentrations in the normal group. Furthermore, notable individual differences occurred in eqAFP concentrations between mares. Equine alpha-fetoprotein seems to be an important indicator of fetal well-being in horses, but there are still some unanswered questions (levels in foals of different age, ponies, and draft horses) regarding this serum protein. Large-scale studies are needed to assess the specificity, sensitivity, and reliability of this test as a possible future diagnostic tool for fetal well-being in horses.


Specificity of two subsets of cytotoxic human gamma delta T-cell clones.
Peripheral blood mononuclear cells were enriched for gamma delta T cells by immunomagnetic separation, stimulated with cells from an allogeneic donor, and cloned. T-lymphocyte clones (TLC) of the two major gamma delta T-cell subsets, BB3+ (i.e. V delta 2+) and delta TCS1+ (i.e. V delta 1/(D)/J delta 1), were obtained. In addition, one gamma delta TLC was BB3- delta TCS1-. All of the BB3+ TLC showed strong cytotoxicity against various allogeneic tumor cell lines, such as Daudi and K562. The cytotoxicity against the tumour cell lines was modulated by MoAb against the gamma delta TcR. The BB3+ TLC were not cytotoxic against B-lymphoblastoid cell lines (B-LCL). In contrast, the delta TCS1+ TLC showed much lower cytotoxic activity against the tumour cell lines, but many were strongly cytotoxic against allogeneic B-LCL. Some of the delta TCS1+ TLC demonstrated HLA-specific cytotoxicity, while other delta TCS1+ TLC had a more broad cytolytic activity against B-LCL. Thus, the two major subtypes of gamma delta T cells from this donor, as defined by MoAb BB3 and delta TCS1, were distinct with respect to recognition specificity.


Increased angiopoietin2 expression is associated with endothelial apoptosis and blood-brain barrier breakdown.
Normal intracerebral and pial vessels show constitutive expression of angiopoietin (Ang) 1 in endothelium while weak Ang2 immunoreactivity is present in occasional vessels. In the early phase postinjury, blood-brain barrier (BBB) breakdown at the lesion site is associated with decreased endothelial Ang1 and increased Ang2 expression, raising the possibility that Ang2 may have a role in early BBB breakdown. In order to determine whether Ang2 can cause BBB breakdown, the effect of recombinant Ang2 on cerebrovascular permeability to horseradish peroxidase (HRP) was studied in normal rat cortex. As hypothesized, Ang2 produced significant BBB breakdown to HRP as compared with vehicle-injected control rats. Since Ang2 is reported to have proapoptotic activity, the possibility that Ang2 may be associated with endothelial apoptosis was investigated in the rat cortical cold injury model over a period of 6 h to 6 days postinjury. Perilesion and pial vessels showed evidence of endothelial apoptosis as demonstrated by active Caspase-3 localization and TUNEL staining. Dual labeling for Ang proteins and active Caspase-3 demonstrated endothelial colocalization of Ang2 with active caspase-3. These data suggest that following injury, Ang2 may play a role in BBB breakdown of perilesional vessels, and it may also be a factor in endothelial cell apoptosis that occurs at days 1 and 2 following the injury.


Elevated production of polymeric and monomeric IgA1 by the bone marrow in IgA nephropathy.
In bone marrow cultures of 15 patients with primary IgA nephropathy we found significantly (P = 0.02) increased synthesis of both monomeric and polymeric IgA1 compared to 23 controls, by using high performance liquid chromatography (HPLC) fractionation of culture supernatants. The relative contribution of polymeric to total IgA1 produced was not different for the two groups. Two-color immunofluorescence studies of the percentage of bone marrow IgA1 plasma cells able to bind secretory component in vitro showed no difference between patients and controls. In the sera of patients with primary IgA nephropathy the relative contribution of IgA1 polymers to total IgA1 was also similar to controls. These results indicate that in IgA nephropathy, the increased IgA production in the bone marrow is restricted to the IgA1 subclass. The production of both monomeric and polymeric IgA1 is increased in patients during a quiescent phase of the disease.


Comparison of mometasone furoate monohydrate (Nasonex) and fluticasone propionate (Flixonase) nasal sprays in the treatment of dust mite-sensitive children with perennial allergic rhinitis.
Various studies have investigated the efficacies of mometasone furoate monohydrate (MFM) and fluticasone propionate (FP) nasal sprays for adults. However, research on their effectiveness for children is limited. This study compares the efficacies of MFM and FP nasal sprays in pediatric patients with perennial-allergic rhinitis. For this study, 94 perennial allergic rhinitis patients aged 6-12 years were randomly assigned to two treatment groups: an MFM group and an FP group. Treatment was provided for 4 weeks. The effects of the two agents were compared using the Pediatric Rhinoconjunctivitis Quality of Life Questionnaire and total symptom scores (TSSs). Nasal-peak expiratory flow rates and eosinophil percentage in nasal smears were also compared between the two groups. Patients in the MFM group exhibited significant improvement in their TSS (t = -2.65, p < 0.05). A detailed TSS analysis showed MFM to be more effective for relieving nasal symptoms, whereas FP was more effective for relieving non-nasal symptoms. Patient questionnaire scores suggested a significant reduction in symptoms for both the MFM (t = -7.23, p < 0.01) and FP (t = -5.43, p < 0.01) groups. The flow rate test results indicated significant improvements in the MFM group (t = 2.27, p < 0.05). Following the 4-week therapy, MFM provided greater improvement compared to FP for symptoms of childhood perennial-allergic rhinitis. Based on their TSSs, the MFM group experienced more effective relief of nasal symptoms, whereas the FP group experienced more effective relief of non-nasal symptoms.


Comparative neuroanatomy of angiotensin II receptor localization in the mammalian hypothalamus.
1. The distribution of angiotensin II (AII) receptor binding sites in the hypothalamus of rat, rabbit, sheep and human was determined by in vitro autoradiography using 125I-[Sar1,Ile8]-AII as radioligand. 2. High receptor binding levels were observed in the continuum of tissue comprising the anterior wall of the third ventricle, including the subfornical organ, the median pre-optic nucleus and the organum vasculosum of the lamina terminalis. 3. High levels of binding sites were also found in the paraventricular and supra-optic nuclei, the median eminence and the arcuate nucleus. 4. These findings demonstrate sites in the hypothalamus of rat, rabbit, sheep and human where AII could exert its known actions on fluid and electrolyte balance, pituitary hormone release and cardiovascular function.


Pediatric otolaryngological relations of velopharyngeal insufficiency.
On the basis of his examinations, the author presents data and gives his opinion on the classification, etiopathogenesis, diagnostics, phonosurgery, and therapy of the otological complications of velopharyngeal insufficiency (VPI). VPI may be organic or functional, produced by congenital or acquired causes, due to paresis or local disorders, but most frequently occurs as a result of cleft palate. Usually, diagnosis is evident; however, the verification of the milder cases of anatomic disproportion and/or muscular dysfunction is sometimes difficult. For the examination of dubious cases the author suggests, apart from the well-known methods (auditive evaluation, function tests, nasopharyngoscopy, velopharyngometry, supersound, X-ray, manometric measurements, speech intelligibility tests, acoustic analyses, etc.), electrophysiological and enzyme-histochemical measurements. Careful examination is most important, also on account of the possible indication of phonosurgery. An operation is to be proposed when a progressive neuro-myogenic process can thus be excluded, or when logopedic treatment is hopeless. The author has done 500 flap operations (as well as 2500 cleft palate and cleft lip ones) in the course of 30 years with a 98% result of anatomical healing. According to the pathological situation he employed 10 variants of the operation. As a result, hyperrhinophony ceased or became minimal in 90% of the cases; speech intelligibility was judged good or excellent in 74%. Functional effects can be influenced by the following: the width of the flap, the functional ability of the pharyngeal muscles, the cause of VPI, the patient's age, and the state of ears and hearing. In case of VPI otological and audiological examinations are routinely required. The author considers adenoidectomy and grommet-insertion to be alternative methods. One of the most important factors in achieving good results is teamwork, which the author discusses on the basis of the model developed at the Heim Pál Hospital for Sick Children, Budapest.


Effects of a salt of cholestyramine and 2-[4-(p-chlorobenzoyl)phenoxy]2-methyl propionic acid (alpha-1081) on biliary lipid secretion in rats.
1 Hypolipidaemic agents may increase biliary cholesterol in man, inducing a supersaturated bile. 2 To evaluate this possible side-effect, we have studied bile lipid secretion over a period of 8 h with intact enterohepatic circulation and 4 h with complete interruption in rats treated for two months with a salt of cholestyramine and 2-[4-(p-chlorobenzoyl)-phenoxy]2-methyl propionic acid (alpha-1081, 1.150 g/kg body wt., daily), cholestyramine (1.125 g/kg body wt. daily), procetofenic acid (25 mg/kg body wt. daily) and saline respectively (six rats for each group). 3 Cholesterol saturation index significantly (P less than 0.005) increased (from 0.21 +/- 0.01 to 0.39 +/- 0.09, mean +/- s.d.), in rats fed with procetofenic acid but it did not in alpha-1081- and cholestyramine-treated animals. 4 Procetofenic acid and, to a lesser extent, cholestyramine increased the bile flow. Procetofenic acid increased cholesterol secretion from 0.45 +/- 0.17 to 0.94 +/- 0.19 mumol kg-1 body wt. h-1 (mean +/- s.d.). 5 Cholestyramine increased both serum cholesterol and bile acid secretion from 0.45 +/- 0.17 to 0.68 +/- 0.10 and 25.8 +/- 9.48 to 39.96 +/- 6.68 mumol kg-1 body wt. h-1 respectively; alpha-1081, on the contrary, had no effect on bile lipid secretion. 6 These data suggest that alpha-1081 may be used as a new hypolipidaemic drug without any risk of increasing cholesterol in bile.


Stem-cell transplantation in multiple myeloma.
In patient with newly diagnosed multiple myeloma (MM), randomized studies have shown that autologous stem-cell transplantation (ASCT) is superior to conventional chemotherapy, and ASCT is now standard care, at least for younger patients. The best conditioning regimen is melphalan 200 mg/m2, and the best stem-cell source is unselected peripheral progenitor cells. Recent results of the IFM94 trial show that double ASCT is superior to single ASCT, at least in patients who do not achieve a 90% response after one transplant. By combining biologic markers (beta2-microglobulin, albumin) and genetic markers (hypodiploidy, chromosome 13 deletion) it is possible to accurately predict prognosis after ASCT. The results of allogeneic SCT remain disappointing due to a high transplant mortality. Strategies combining ASCT and reduced-intensity allogeneic SCT are currently being studied.


Home-based versus hospital-based high-intensity interval training in cardiac rehabilitation: a randomized study.
High-intensity interval training (HIT) as exercise therapy is gradually implemented in cardiac rehabilitation as the cardiovascular benefits from exercise is intensity dependent. However, in previous studies, HIT has been performed with strict supervision. The aim of the study was to assess the feasibility and effectiveness of different modes of HIT in cardiac rehabilitation. a randomized clinical study. Ninety participants with coronary artery disease (80 men/10 women, mean age 57 ± 8 years) were randomly assigned to one of three exercise modes: group exercise (GE), treadmill exercise (TE), or home-based exercise (HE). HIT was performed twice a week for 12 weeks with an exercise intensity of 85-95% of peak heart rate. The primary outcome measure was change in peak oxygen uptake (peak VO2). Eighty-three participants (92%) completed the intervention without any severe adverse events. Peak VO2 increased from 34.7 ± 7.3 to 39.0 ± 8.0 ml/kg/min, 32.7 ± 6.5 to 36.0 ± 6.2 ml/kg/min, and 34.4 ± 4.8 to 37.2 ± 5.2 ml/kg/min in TE, GE, and HE, respectively. Mean group difference for TE vs. HE was 1.6 ml/kg/min (95% confidence interval, CI, 0.7 to 3.1, p = 0.02), TE vs. GE 1.1 ml/kg/min (95% CI-0.5 to 2.5, p = 0.27), and GE vs. HE 0.6 ml/kg/min (95% CI -1.0 to 2.1, p = 1). However, on-treatment analysis showed no significant difference between groups. HIT was efficiently performed in three settings of cardiac rehabilitation, with respect to target exercise intensity, exercise attendance, and increase in peak VO2. Exercise mode was not essential for exercise capacity.


Immunoglobulin M anti-hepatitis A virus determination reorienting gradient centrifugation for diagnosis of Acute Hepatitis A.
The persistence of antibody to hepatitis A antigen (anti-HAV) of the immunoglobulin M (IgM) class was evaluated in 88 sera of 51 acute hepatitis A patients. IgM was separated from IgG by a 2-h reorienting sucrose gradient ultracentrifugation, and the titer of anti-HAV was determined in the IgG- and IgM-containing fractions by solid-hase radioimmunoassay. IgM anti-HAV was the predominating antibody at onset of jaundice and persisted in these patients for at least 60 days, but not longer than 115 days. The demonstration of IgM anti-HAV is therefore a valuable tool for the diagnosis of recent hepatitis A infection.


Influence of galanin and serotonin on the endocrine response to Hexarelin, a synthetic peptidyl GH-secretagogue, in normal women.
Hexarelin (HEX) is a synthetic GH-secretagogue (GHS) which acts on specific receptors either at the pituitary or the hypothalamic level to stimulate GH release both in animal and in man. Like other GHS, HEX possesses also PRL-, ACTH- and cortisol (F)-releasing activity but the mechanisms underlying these effects are even less clear. On the other hand, galanin (GAL) and serotonin play an important role in the neural control of GH, PRL and ACTH secretion both in animal and in man. In order to study the interaction between HEX and GAL and to verify whether serotoninergic mechanisms underly the endocrine effects of GHS, in 12 normal young volunteers (24-30 yr) the following tests were performed: group A (N = 5), HEX (2.0 micrograms/kg i.v. at 0 min), GAL (15.0 micrograms/kg i.v. from 0 to 60 min) and HEX + GAL; group B (N = 7), HEX alone and preceeded by cyproeptadine (CYPRO, 8 mg os at -60 min). In group A, the GH response to HEX (1204.2 +/- 312.9 micrograms*min/L) was higher (p < 0.05) than that to GAL alone (305.6 +/- 35.5 micrograms*min/L) and was not modified by GAL co-administration (1021.8 +/- 249.9 micrograms*min/L). PRL secretion was increased to the same extent by HEX and GAL (507.9 +/- 81.1 and 743.0 +/- 164.7 micrograms*min/L) which showed no interaction (603.5 +/- 75.7 micrograms*min/L). HEX elicited an increase in both ACTH and F secretion (924.5 +/- 169.7 pg*min/ml and 6131.3 +/- 616.6 micrograms*min/L) while GAL had no effect when given alone (759.5 +/- 185.5 pg*min/ml and 5350.3 +/- 755.6 micrograms*min/L) and did not modify the effect of HEX (891.3 +/- 159.2 pg*min/ml and 5877.8 +/- 554.4 micrograms*min/L). In group B, the GH response to HEX (1636.4 +/- 267.5 micrograms*min/L) was blunted by CYPRO (1164.8 +/- 212.3 micrograms*min/L) but this difference did not attained statistical significance. On the other hand, CYPRO did not modify the HEX-induced PRL (599.5 +/- 129.2 vs 638.9 +/- 131.9 micrograms*min/L), ACTH (1282.8 +/- 222.0 vs 1330.2 +/- 347.0 pg*min/ml) and F response (4738.3 +/- 355.3 vs 4580.9 +/- 857.3 micrograms*min/L). Our present data demonstrate that Hexarelin has no interaction with galanin; thus thereotically, the stimulatory effect of GHS on GH and PRL secretion could involve, at least partially, a galanin-mediated mechanism. On the other hand, our data demonstrate that serotonin does not mediate the stimulatory effect of GHS on PRL, ACTH and cortisol; the intrinsic anticholinergic property of cyproeptadine could account for the trend toward its blunting effect on the GH response to Hexarelin.


Context is key: Modulated protein multivalency in disease.
In this issue of Molecular Cell, Song et al. demonstrate that mutations to the YEATS domain of ENL aberrantly activate gene expression by forming condensates on specific genomic loci. By using diverse experimental approaches, the authors dissect the molecular underpinnings of ENL mutant condensate formation.


MiR-125a/b regulates the activation of cancer stem cells in paclitaxel-resistant colon cancer.
In this study, we investigated ALDH1A3, Mcl1, and miR-125a/b expression in HT29 cells and the effect of miR-125a/b on ALDH1A3 and Mcl1 expression. Our results showed that low expression of miR-125a/b and high expression of ALDH1A3 and Mel1 were observed in both ALDH1-positive HT29 and HT29-taxol cells. Overexpression of miR-125a/b significantly inhibited ALDH1A3 and Mcl1 expression, reduced cell survival, and increased cell apoptosis in HT29-taxol cells. Injection of miR-125a/b expression vector inhibited tumor growth in xenograft HT29-taxol mouse model. The current study suggested that miR-125a/b expression plays a key role in chemoresistance through upregulating ALDH1A3 and Mcl1 gene expression.


Silent mutations in ribosomal protein genes are associated with high-risk clones of carbapenem-resistant Acinetobacter baumannii prevalent in Brazil.
To analyze the relationship of ribosomal protein mutations and clonality of high-risk clones Acinetobacter baumannii. Seventy-nine carbapenem-resistant A. baumannii were subjected to whole-genome sequencing (Illumina NextSeq), and codifying sequences of ribosomal proteins were extracted and screened for mutations. MALDI-TOF MS analysis (Bruker Biotyper) and Spectra data from MALDI-TOF was employed to generate a dendrogram based on principal component analysis (PCA) data. Clones were identified by Multilocus sequencing typing (MLST) based on WGS. Ribosomal RNA protein sequences extracted from the genomes identified mutations that were associated with clonal complexes, but most of them were silent. PCA did not cluster the isolates according to their clonality identified by MLST. By comparing the nucleotide and amino acid sequences of diversified A. baumannii, and Bruker Biotyper profiles, we showed that silent mutations in ribosomal RNA nucleotides are associated with clonal complexes, but since most of the mutations were silent, MALDI-TOF MS raw data was not a useful tool for typing the high-risk clones of this species.


Systematic expression profiling analysis mines dys-regulated modules in active tuberculosis based on re-weighted protein-protein interaction network and attract algorithm.
About 90% of tuberculosis (TB) patients latently infected with Mycobacterium tuberculosis (Mtb) show no symptoms, yet have a 10% chance in lifetime to progress active TB. Nevertheless, current diagnosis approaches need improvement in efficiency and sensitivity. The objective of this work was to detect potential signatures for active TB to further improve the understanding of the biological roles of functional modules involved in this disease. First, targeted networks of active TB and control groups were established via re-weighting protein-protein interaction (PPI) networks using Pearson's correlation coefficient (PCC). Candidate modules were detected from the targeted networks, and the modules with Jaccard score >0.7 were defined as attractors. After that, identification of dys-regulated modules was conducted from the attractors using attract method, Subsequently, gene oncology (GO) enrichment analyses were implemented for genes in the dys-regulated modules. We obtained 33 and 65 candidate modules from the targeted networks of control and active TB groups, respectively. Overall, 13 attractors were identified. Using the cut-off criteria of false discovery rate <0.05, there were 4 dys-regulated modules (Module 1, 2, 3, and 4). Based on the GO annotation results, genes in Modules 1, 2 and 4 were only involved in translation. Most genes in Module 1, 2 and 4 were associated with ribosomes. Accordingly, these dys-regulated modules might serve as potential biomarkers of active TB, facilitating the development for a more efficient, and sensitive diagnostic assay for active TB.


Early experience with lidocaine patch for postoperative pain control after laparoscopic ventral hernia repair.
Reduced postoperative pain is one of the many factors that have driven the growing emphasis on the role of laparoscopic surgery for surgical management. Several studies have documented the advantages of the laparoscopic repair of ventral hernias compared to the open ventral herniorraphy. However, the laparoscopic approach may be associated with more postoperative pain initially. In this preliminary study, we present data from our early experience with the use of a lidocaine patch for pain control in the immediate postoperative period following laparoscopic ventral hernia repair (LVH). Thirty consecutive patients underwent laparoscopic ventral herniorraphy (LVH) and were selected randomly and placed into one of two groups. In one group, we placed a lidocaine patch (LP) (Lidoderm, Endo Pharmaceuticals, Inc., Chadds Ford, PA) on the anterior abdominal wall corresponding to the placement site of the underlying mesh in fifteen patients (Group A). In the second group, we did not place a LP on the abdominal wall of fifteen consecutive patients (Group B). We assessed all patients according to their demographic data, Body Mass Index (BMI), American Society of Anesthesiologists (ASA) score, the size of the abdominal wall defect (AWD), area of mesh (size) used, operative time, length of hospital stay (LOA), morbidity, and the individual patient's pain score at discharge, two weeks and two months postoperatively. The two groups were similar with respect to demographics, BMI, ASA, AWD, size of mesh, LOS and morbidity. Group A had a statistically significant reduction in their postoperative pain score at discharge when compared to Group B (3.13+/-1.68 and 4.8+/-1.42, respectively, p value=0.0067). In this preliminary study, the use of a lidocaine patch in the management of postoperative pain following laparoscopic ventral herniorraphy is a safe and promising modality to consider in the management of postoperative pain control.


Pitsubcosides A-L, highly esterified eudesmane sesquiterpenoid glycosides with antibacterial activity from Pittosporum subulisepalum and their mechanism.
Plants from the genus Pittosporum are traditionally used as antibacterial, antifungal and antiviral agents. A bioassay evaluation of the extract of Pittosporum subulisepalum revealed antibacterial activity. This study focused on the discovery of the antibacterial metabolism in P. subulisepalum, as well as the modes of action of its active components. A chemical investigation of an ethyl acetate (EtOAc) extract of the aerial parts of P. subulisepalum led to the isolation of 12 previously undescribed eudesmane sesquiterpenoid glycoside esters (ESGEs), pitsubcosides A-L (1-12). Their structures were elucidated by extensive spectroscopic analysis, including one- and two-dimensional NMR, high-resolution electrospray ionization mass spectrometry, electronic circular dichroism spectra and single-crystal X-ray crystallography analysis or by comparing with authentic samples. The new ESGEs were characterized by their highly esterified glycoside moieties. Among them, compounds 1-3, 5 and 8 showed a moderate inhibitory effect against Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Bacillus cereus, Bacillus subtilis, Pseudomonas syringae pv. actinidiae (Psa) and Erwinia carotovora with minimum inhibitory concentrations (MICs) ranging from 3.13 to 100 μm. Among them, compounds 3 and 5 showed remarkable antibacterial activity against S. aureus and Psa with MIC values of 6.25 and 3.13 μm, respectively. Live bacterial mass and the biofilms of S. aureus and Psa were quantified using methyl tetrazolium and crystal violet assays. Fluorescence microscopy and scanning electron microscopy experiments revealed an antibacterial mechanism of cell membrane architectural disruption. The results suggest that ESGEs possess great potential for the development of antibacterial agents to control plant pathogens. © 2023 Society of Chemical Industry.


Analyzing PACS Usage Patterns by Means of Process Mining: Steps Toward a More Detailed Workflow Analysis in Radiology.
In this paper, statistical analysis and techniques from process mining are employed to analyze interaction patterns originating from radiologists reading medical images in a picture archiving and communication system (PACS). Event logs from 1 week of data, corresponding to 567 cases of single-view chest radiographs read by 14 radiologists, were analyzed. Statistical analysis showed that the numbers of commands and command types used by the radiologists per case only have a slightly positive correlation with the time to read a case (0.31 and 0.55, respectively). Further, one way ANOVA showed that the factors time of day, radiologist and specialty were significant for the number of commands per case, whereas radiologist was also significant for the number of command types, but with no significance of any of the factors on time to read. Applying process mining to the event logs of all users showed that a seemingly "simple" examination (single-view chest radiographs) can be associated with a highly complex interaction process. However, repeating the process discovery on each individual radiologist revealed that the initially discovered complex interaction process consists of one group of radiologists with individually well-structured interaction processes and a second smaller group of users with progressively more complex usage patterns. Future research will focus on metrics to describe derived interaction processes in order to investigate if one set of interaction patterns can be considered as more efficient than another set when reading radiological images in a PACS.