Ligand-Controlled Palladium-Catalyzed Chemoselective Multicomponent Reaction of Olefin-Tethered Aryl Halides, Isocyanides, and Carboxylic Acids: Diversified Synthesis of Imides.
The first palladium-catalyzed, ligand-controlled chemoselective synthesis of imides has been achieved. An orthogonal set of conditions has been developed for multicomponent reaction of various olefin-tethered aryl iodides, isocyanides, and carboxylic acids. Alkylimides ("cyclization on" products) via arylimidation of tethered unactivated alkenes and aryl imides ("cyclization off" products) via direct imidation of aryl iodides were obtained in good to excellent yields with good to excellent selectivity. Computational studies were performed to gain insight into the origin of the high levels of chemoselectivity observed.


Shaping the future.
Last week BVA members gathered in Belfast to hear about their organisation's future plans, welcome new officers and celebrate excellence in the profession.


Levels of Systemic Low-grade Inflammation in Pregnant Mothers and Their Offspring are Correlated.
High sensitivity C-reactive protein (hs-CRP) is a marker of systemic low-grade inflammation and associated with chronic inflammatory diseases. It is unknown whether maternal and infant hs-CRP levels are correlated and little is known about risk factors in early childhood. Hs-CRP were measured in mothers during pregnancy week 24 (N = 690), and one-week postpartum (N = 675) and in their children age 6 mo (N = 640) enrolled in the Copenhagen Prospective Studies on Asthma in Childhood2010 (COPSAC2010) cohort. The risk factor analysis included anthropometrics, environmental exposures and CRP-Genetic Risk Score (GRS). Mother's body mass index (BMI), use of antibiotics, smoking, cesarean delivery and season were associated with higher maternal hs-CRP level, whereas higher social circumstances were associated with lower hs-CRP level (p < 0.05). Child's BMI, siblings, bacterial airway colonization, current infection, CRP-genetic risk score and season were associated with higher hs-CRP at age 6 mo (all p < 0.05). Mother's hs-CRP level in pregnancy week 24 was associated with hs-CRP level in the child at 6 mo: β-coefficient = 0.11 [95% CI: 0.01-0.20], R2 = 0.22, p = 0.03. The association was unchanged adjusted for all significant risk factors. Systemic low-grade inflammation in pregnant mothers and their offspring is correlated independently of BMI, environmental exposures and genetic risk factors.


Transport of ethanol in baker's yeast.
Ethanol is transported into various strains of baker's yeast by simple diffusion (no effect of inhibitors and a linear concentration dependence of the initial rate of uptake and final distribution in cells). It distributes itself in 96.6 +/- 16.2% of intracellular water.


The safety and usefulness of high-dose-rate endoluminal brachytherapy as a boost in the treatment of patients with esophageal cancer with external beam radiation with or without chemotherapy.
This study reports the results of a single-institution experience with high-dose-rate brachytherapy (HDRBT) used as a boost in the treatment of esophageal cancer with external beam radiation therapy (ERT) with or without chemotherapy. Patients without evidence of metastatic disease were identified. HDRBT was given before ERT with a dose of 20 Gy in 5 fractions. Patients with a Karnofsky performance of more than 70 received treatment with 50 Gy in 25 fractions and concurrent 5-fluorouracil and cis-platinum during Weeks 1 and 5, whereas patients with a Karnofsky performance of less than 70 were treated with radiation therapy alone with 35 Gy in 14 fractions. Fifty-three patients received HDRBT treatment with combined ERT and chemotherapy and 17 patients with ERT alone. The incidence of acute bone marrow toxicity was 55% Grade 2 and 15% Grade 3, and 85% of patients had Grade 2 esophagitis. With a median follow-up time of 26 months, the median survival was 21 months; the 2-year local recurrence was 25%, and the 5-year survival rate was 28%. HDRBT is safe and beneficial for local control in the radical treatment of patients with esophageal cancer.


Liposarcoma of the larynx: a multicentric or a metastatic malignancy.
The third case of liposarcoma of the larynx, this one arising from the preepiglottic space, is presented. The report is unique in so far as the patient previously had been treated for a liposarcoma in another anatomic region. The diagnosis in this case was in doubt until electron microscopic studies were done. Since the histopathology of the laryngeal and the previous liposarcoma were different, the question of metastasis versus multicentricity was raised. Other discussions of liposarcomas over the past three decades have not resolved this aspect of their behavior completely. In this instance, after considering avenues of metastatic spread in conjuction with the histopathology, it would appear that the laryngeal lesion was a second primary and not a metastasis.


Algorithms for Regular Tree Grammar Network Search and Their Application to Mining Human-viral Infection Patterns.
Network querying is a powerful approach to mine molecular interaction networks. Most state-of-the-art network querying tools either confine the search to a prespecified topology in the form of some template subnetwork, or do not specify any topological constraints at all. Another approach is grammar-based queries, which are more flexible and expressive as they allow for expressing the topology of the sought pattern according to some grammar-based logic. Previous grammar-based network querying tools were confined to the identification of paths. In this article, we extend the patterns identified by grammar-based query approaches from paths to trees. For this, we adopt a higher order query descriptor in the form of a regular tree grammar (RTG). We introduce a novel problem and propose an algorithm to search a given graph for the k highest scoring subgraphs matching a tree accepted by an RTG. Our algorithm is based on the combination of dynamic programming with color coding, and includes an extension of previous k-best parsing optimization approaches to avoid isomorphic trees in the output. We implement the new algorithm and exemplify its application to mining viral infection patterns within molecular interaction networks. Our code is available online.


Community-based alcohol education intervention (THEATRE) study to reduce harmful effects of alcohol in rural Sri Lanka: design and adaptation of a mixed-methods stepped wedge cluster randomised control trial.
Alcohol consumption is a leading cause of mortality, morbidity and adverse social sequelae in Sri Lanka. Effective community-based, culturally adapted or context-specific interventions are required to minimise these harms. We designed a mixed-methods stepped wedge cluster randomised control trial of a complex alcohol intervention. This paper describes the initial trial protocol and subsequent modifications following COVID-19. We aimed to recruit 20 villages (approximately n=4000) in rural Sri Lanka. The proposed intervention consisted of health screening clinics, alcohol brief intervention, participatory drama, film, and public health promotion materials to be delivered over 12 weeks.Following disruptions to the trial resulting from the Easter bombings in 2019, COVID-19 and a national financial crisis, we adapted the study in two main ways. First, the interventions were reconfigured for hybrid delivery. Second, a rolling pre-post study evaluating changes in alcohol use, mental health, social capital and financial stress as the primary outcome and implementation and ex-ante economic analysis as secondary outcomes. The original study and amendments have been reviewed and granted ethical approval by Rajarata University of Sri Lanka (ERC/2018/21-July 2018 and February 2022) and the University of Sydney (2019/006). Findings will be disseminated locally in collaboration with the community and stakeholders.The new hybrid approach may be more adaptable, scalable and generalisable than the planned intervention. The changes will allow a closer assessment of individual interventions while enabling the evaluation of this discontinuous event through a naturalistic trial design. This may assist other researchers facing similar disruptions to community-based studies. The trial is registered with the Sri Lanka Clinical Trials Registry; https://slctr.lk/trials/slctr-2018-037.


Digital signal processing of stridor and snoring in children.
Stridor and snoring are common signs of upper airway obstruction. The nature and characteristics of the stridor and snoring depend upon the site of obstruction. Sophisticated analysis of these sounds may provide important information concerning the source of the sound helping to assess the patient more objectively. The preliminary results of computerized digital analysis of stridor and snoring sounds are presented in 5 children. Two main programs were applied to analyse the signal: the Power Spectral Density (PSD) function and the Estimated Cross-sectional Area (ECSA). A consistent pattern according to the site of the produced sound was seen. Further acoustical analyses are needed to standardize this method and to program the computer to indicate the various sites of lesions.


Reovirus intermediate subviral particles constitute a strategy to infect intestinal epithelial cells by exploiting TGF-β dependent pro-survival signaling.
Intestinal epithelial cells (IECs) constitute the primary barrier that separates us from the outside environment. These cells, lining the surface of the intestinal tract, represent a major challenge that enteric pathogens have to face. How IECs respond to viral infection and whether enteric viruses have developed strategies to subvert IECs innate immune response remains poorly characterized. Using mammalian reovirus (MRV) as a model enteric virus, we found that the intermediate subviral particles (ISVPs), which are formed in the gut during the natural course of infection by proteolytic digestion of the reovirus virion, trigger reduced innate antiviral immune response in IECs. On the contrary, infection of IECs by virions induces a strong antiviral immune response that leads to cellular death. Additionally, we determined that virions can be sensed by both TLR and RLR pathways while ISVPs are sensed by RLR pathways only. Interestingly, we found that ISVP infected cells secrete TGF-β acting as a pro-survival factor that protects IECs against virion induced cellular death. We propose that ISVPs represent a reovirus strategy to initiate primary infection of the gut by subverting IECs innate immune system and by counteracting cellular-death pathways.


Electrically enhanced ethanol fermentation by Clostridium thermocellum and Saccharomyces cerevisiae.
Ethanol production by Clostridium thermocellum ATCC 35609 and Saccharomyces cerevisiae ATCC 26603 was improved in an electrochemical bioreactor system. It was increased by 61% with Cl. thermocellum and 12% with S. cerevisiae in the presence of -1.5 V of electric potential. These increases were attributed to high production rates due to regeneration and availability of increased reduced equivalents in the presence of electric potential. The electric current caused considerable shift in the metabolite concentrations on a molar basis in Cl. thermocellum fermentation but less in S. cerevisiae fermentation. Increasing electric potential in Cl. thermocellum fermentation resulted in less acetate and more lactate production. Acetate production was also reduced with increased electric potential in S. cerevisiae fermentation. The high electric potential of -5 V adversely affected the Cl. thermocellum fermentation, but not the S. cerevisiae fermentation even at a high electric potential of -10 V.


Effects of thickness, processing technique, and cooling rate protocol on the flexural strength of a bilayer ceramic system.
To determine whether the thickness, processing technique, and cooling protocol of veneer ceramic influence the flexural strength of a bilayer ceramic system. Sixty-four bar-shaped specimens (20mm×4mm×1mm) of yttria-stabilized tetragonal zirconia (Vita In-Ceram YZ, Vita) were fabricated (ISO 6872) and randomly divided into 8 groups (n=8) according to the factors "processing technique" (P - PM9 and V - VM9), "thickness" (1mm and 3mm), and "cooling protocol" (S - slow and F - fast). The veneer ceramics were applied only over one side of the bar-shaped specimens. All specimens were mechanically cycled (2×10(6) cycles, 84N, 3.4Hz, in water), with the veneer ceramic under tension. Then, the specimens were tested in 4-point bending (1mm/min, load 100kgf, in water), also with the veneer ceramic under tension, and the maximum load was recorded at first sign of fracture. The flexural strength (σ) was calculated, and the mode of failure was determined by stereomicroscopy (30×). The data (MPa) were analyzed statistically by 3-way ANOVA and Tukey's test (α=0.05). ANOVA revealed that the factor "thickness" (p=0.0001) was statistically significant, unlike the factors "processing technique" (p=0.6025) and "cooling protocol" (p=0.4199). The predominant mode of failure was cracking. The thickness of the veneer ceramic has an influence on the mechanical strength of the bilayer ceramic system, regardless of processing technique and cooling protocol of the veneer ceramic.


Structure-activity relationship studies on a series of cyclohexylpiperazines bearing a phanylacetamide as ligands of the human melanocortin-4 receptor.
Synthesis and structure-activity relationship studies of a series of cyclohexylpiperazines bearing an amide side chain as ligands of the MC4 receptor are discussed. Compounds such as 11i from this series are potent agonists (EC(50)=33nM, IA=96%).


Molecular and biosynthetic heterogeneity of fucosyl glycoproteins associated with rat brain synaptic functions.
The composition and biosynthesis of fucosyl glycoproteins present in rat brain synaptic membranes and synaptic junctions were investigated. Reaction with 125I-labelled fucose-binding protein (Lotus tetragonolobus) following sodium dodecyl sulphate gel electrophoresis identified 6--8 fucosyl glycoproteins in synaptic membranes but only three major high molecular classes (Mr = 180 000, 130 000 and 110 000) in synaptic junctions. Affinity chromatography on concanavalin A-Sepharose resolved each of the synaptic junctional fucosyl glycoproteins into concanavalin A-positive and negative components indicating the presence of at least six high molecular weight fucosyl glycoproteins in synaptic junctions. Following the administration of [3H]fucose synaptic membranes, synaptic junctions and post-synaptic densities incorporated isotope, the order of relative specific activities being synaptic membranes greater than synaptic junctions greater than post-synaptic densities. Fractionation of [3H]fucose-labelled synaptic junctions on concanavalin A-Sepharose revealed a time-dependent increase in the percentage of isotope associated with the concanavalin A-positive glycoproteins. The results demonstrate both molecular and biosynthetic heterogeneity of fucosyl glycoproteins associated with synaptic junctions.


Menkes' kinky hair disease.
Four new cases of Menkes' kinky hair disease are reported with special attention to the vascular and particularly the cerebral vascular changes.


Bilateral pelvic discontinuity: a unique condition characterized by high failure rates of current treatment.
Bilateral pelvic discontinuity is characterized by complete dissociation of the superior and inferior pelvis secondary to bone loss or fracture. The end result is a freely mobile inferior pelvis at the level of each discontinuity which presents a significant reconstruction challenge. This clinical entity has not been described previously, and the results of surgical treatment are not known. We retrospectively reviewed all identified cases of pelvic discontinuity (PD) treated with revision THA at one institution. We identified 133 pelvic discontinuities. Within this group, 6 patients had bilateral simultaneous PDs. Preoperative, intraoperative, and postoperative data and radiographic imaging were reviewed preoperatively and postoperatively for the characteristics of the dissociation and assessing PD healing and fixation of components after surgery. There were no preoperative factors that could distinguish these patients from the rest of the group of discontinuities (3 rheumatoid arthritis, 2 osteonecrosis of the femoral head, 1 developmental dysplasia). The reconstructions performed included 2 cup/cage, 5 posterior plating and uncemented cup, 3 cage alone, and 2 cups only. Ten of 12 hips had at least 1 complication postoperatively. At final follow-up, only 1 patient (17%) had radiographic evidence that both discontinuities had healed (posterior plate with uncemented cup). Bilateral pelvic discontinuity is rare but presents the surgeon with a major reconstructive challenge. Only 1 patient went on to radiographic healing with current treatment strategies. Continued motion of the contralateral pelvic dissociation may account for the high failure rates. Surgeons should be aware of the challenges presented by this diagnosis and develop strategies to improve outcomes.


Asenic removal from groundwater using granular chitosan-titanium adsorbent.
Arsenic (As) contamination poses an urgent environmental risk, and its removal from groundwater remains a challenge due to the lack of efficient adsorbents. Herein, a novel granular chitosan-titanium (CS-Ti) adsorbent was fabricated by the sol-gel method. Batch experiments show that As(V) adsorption on CS-Ti followed the pseudo-second-order kinetic model, and the adsorption isotherm conformed to the Freundlich model with the correlation coefficient of 0.99. In situ FTIR spectra revealed that the CS-Ti adsorbent was composed of amorphous TiOx and chitosan by forming C-O-Ti and N-Ti bonds, and the amorphous TiOx was responsible for As(V) adsorption. Rapid small-scale column tests show that 165.6 μg/L of As in groundwater were effectively removed in approximately 126-bed volumes, and the spent adsorbents were regenerated with 0.01 mol/L NaOH and maintained the adsorption efficiency after four cycles. This study provides a simple and practical route to fabricate adsorbents for water treatment.


Prolyl hydroxylase 3 interacts with Bcl-2 to regulate doxorubicin-induced apoptosis in H9c2 cells.
Prolyl hydroxylases (PHDs) are dioxygenases that use oxygen as a co-substrate to hydroxylate proline residues. Three PHD isoforms (PHD1, PHD2 and PHD3) have been identified in mammalian cells. PHD3 expression is upregulated in some cardiac diseases such as cardiomyopathy, myocardial ischemia-reperfusion injury and congestive heart failure, all of which are associated with apoptosis. However, the role of PHDs in cardiomyocyte apoptosis remains unknown. Here, we have found that exposure of embryonic rat heart-derived H9c2 cells to doxorubicin (DOX) induced cell apoptosis as evaluated by caspase-3/7 activity, mitochondrial membrane potential (Δψm) and cell viability, and that this apoptosis was linked to PHD3 upregulation. PHD inhibition or PHD3 silencing substantially ameliorated DOX-induced apoptosis, but PHD1 or PHD2 knockdown did not significantly influence apoptosis. Furthermore, immunoprecipitation experiments showed that PHD3 upregulation reduced the formation of the Bax-Bcl-2 complex, inhibiting the anti-apoptotic effect of Bcl-2. Thus, PHD3 upregulation may be partially responsible for DOX-induced cardiomyocyte apoptosis via its interaction with Bcl-2. Inhibition of PHD3 is likely to be cardioprotective against apoptosis in some heart disorders.


Brain creatine phosphate and creatine kinase in mice fed an analogue of creatine.
Brain phosphocreatine (PCr) concentration and creatine kinase (CK) activity have been studied by 31P nuclear magnetic resonance (NMR) spectroscopy in mice fed an analogue of creatine, beta-guanidinopropionic acid (GPA). The phosphorylated analogue (GPAP), which almost completely replaces PCr in skeletal muscle, is a poor substrate for CK. Mice, which received GPA in food (2%) and water (0.5%) for up to 9 months beginning at 35 days of age, were normal in appearance and activity. Maximal brain GPAP concentration, reached after two weeks of feedings, was approximately equal to the concentration of PCr. The concentration of PCr decreased at least 20% relative to that of the nucleoside triphosphates. When GPA feedings were stopped, GPAP disappeared in about 20 days from skeletal muscle, but only after 40-50 days from brain. Steady-state NMR saturation transfer studies showed a markedly reduced chemical exchange rate from PCr to ATP in brains of GPA-fed mice. These results suggest a compartmentation of brain PCr. The GPA-accessible PCr compartment has a slow rate of PCr turnover compared to skeletal muscle. The slow reaction rate of the GPA-inaccessible PCr as a CK substrate is consistent with the hypothesis that this residual PCr is the same compartment which is stable in hypoxic or seizing animals.


Deprotonation in anodic methoxylation of fluoroethyl phenyl sulfides using site-isolated heterogeneous bases.
On the basis of the concept of site isolation in electrochemical reactions, we have successfully demonstrated acceleration of the deprotonation step in anodic methoxylation of fluoroethyl phenyl sulfides using silica gel supported bases.


Elevated C-reactive protein levels during first trimester of pregnancy are indicative of preeclampsia and intrauterine growth restriction.
C-reactive protein (CRP) is a marker of tissue damage and inflammation. Maternal levels of CRP are elevated in overt preeclampsia, but there is still debate about its use as a predictive marker for preeclampsia during the first and second trimesters of pregnancy. In this study, we measured CRP levels during the first trimester of pregnancy in women who later developed preeclampsia or gave birth to a growth-restricted baby. In total, 107 women from a low-risk population participated in the study, six women developed preeclampsia and nine gave birth to a growth-restricted baby. Although there is a large overlap in measured CRP levels between the three groups, mean CRP levels were significantly elevated in women who later developed preeclampsia (P=0.031) or delivered a growth-restricted baby (P=0.041) when compared with women from the control group, matched for maternal and gestational age, parity, and gravidity. This study shows that in a low-risk population, CRP levels are already elevated between weeks 10 and 14 in pregnant women who develop preeclampsia or deliver a growth-restricted baby.


PET/CT evaluation of 18F-FDG uptake in pericoronary adipose tissue in patients with stable coronary artery disease: Independent predictor of atherosclerotic lesions' formation?
Inflammatory infiltrations in EAT which releases inflammatory cytokines correspond anatomically to the atheromatous plaques in underlying coronary vessels. However, it is unknown whether inflammatory activity of pericoronary adipose tissue (PCAT) promotes coronary atherosclerosis. 35 non-diabetic patients with confirmed CAD and 35 non-CAD controls matched for age and BMI underwent 18F-FDG-PET/CT. Maximal SUV normalized by LA blood activity was measured on the sections corresponding to the respective coronaries (RCA, LCX, LAD), as well, as in subcutaneous fat, visceral fat, and epicardial fat. Extent of CAD was determined by % stenosis in segments corresponding to 18F-FDG-PET/CT sections in coronarography using quantitative coronary analysis. PCAT SUV was significantly greater than SUV in other fat locations, as well as PCAT SUV in the controls. In CAD patients with BMI >25, PCAT SUV was positively related to % stenosis of a respective coronary artery (RCA: 0.43; P < .05; LCX 0.58; P < .05; LAD 0.65; P < .05). PCAT SUV was the only independent predictor of coronary stenosis of LAD and RCA. Inflammatory activity of PCAT is greater than in other fat locations, in CAD is greater than in non-CAD controls, and is independently associated with coronary stenosis. In overweight patients, PCAT SUV correlates with the extent of CAD.


Perilipin 4 Protein: an Impending Target for Amyotrophic Lateral Sclerosis.
The pathogenesis of amyotrophic lateral sclerosis (ALS) might exist some relationships with the abnormal lipidomic metabolisms. Therefore, we observed and analyzed the alteration of perilipin 4 (PLIN 4) distribution in the anterior horns (AH); the central canals (CC) and its surrounding gray matter; the posterior horns (PH); and the anterior, lateral, and posterior funiculus (AF, LF, and PF) of the cervical, thoracic, and lumbar segments, as well as the alteration of PLIN 4 expression in the entire spinal cords at the pre-onset, onset, and progression stages of Tg(SOD1*G93A)1Gur (TG) mice and the same period of wild-type(WT) by fluorescent immunohistochemistry, the Western blot, and the image analysis. Results showed that the PLIN 4 distributions in the spinal AH, CC and its surrounding gray matter, PH, AF, and PF of the cervical, thoracic, and lumbar segments in the TG mice at the pre-onset, onset, and progression stages significantly increased compared with those at the same periods of WT mice; the gray matter was especially significant. No significant changes were detected in the LF. PLIN 4 extensively distributed in the neurons and the proliferation neural cells. The PLIN 4 distributions significantly gradually increased from the pre-onset to onset to progression stages, and significantly correlated with the gradual increase death of neural cells. Total PLIN 4 expression in the spinal cords of TG mice significantly increased from the pre-onset, to onset, and to progression stages compared with that in the WT mice. Our data suggested that the PLIN 4 distribution and expression alterations might participate in the death of neural cells in the pathogenesis of ALS through modulating the lipidomic metabolisms and the neural cell proliferation.


Gasoil removal from aqueous solution using magnetic metal-organic framework adsorbent based on the cellulosic fibrous of Prosopis farcta plant.
Recently, the leakage of Gasoil and other petroleum substances into the seas, surface water, and wastewater has become a global problem; therefore, providing a solution to remove these pollutants seems vital. In the current research, we investigated the removal of floating Gasoil from aqueous solutions. First, the magnetic metal-organic framework was prepared as a new adsorbent based on the cellulosic fibrous of the Prosopis farcta plant (magnetic- cellulose@MIL-53(Fe) carbon aerogel). Using design of experiment, the effect of parameters pH, Gasoil concentration, and adsorbent weight on Gasoil removal were investigated. The adsorbent prepared under optimal parameters can remove 100% floating Gasoil from the aqueous solution. The adsorption capacity of the magnetic- cellulose@MIL-53 (Fe) carbon aerogel is 7.48 g.g-1, which is almost 100 times more than other Fe-based adsorbents. The study of the effect of time showed that the adsorption of Gasoil by the adsorbent is not dependent on time. Gasoil adsorption on magnetic- cellulose@MIL-53(Fe) carbon aerogel follows the Freundlich isotherm with a correlation coefficient of 0.9933. Thermodynamic factors Gibbs free energy, enthalpy, and entropy changes have been calculated. Accordingly, magnetic- cellulose @MIL-53(Fe) carbon aerogel has rapid separation and high stability, and it could be used as a good adsorbent to remove Gasoil from an aqueous solution. With good cycling stability of 86% retention of the initial adsorption value after ten adsorption/desorption cycles.


Tubulo-interstitial alterations in type I membranoproliferative glomerulonephritis. An investigation of 259 cases.
A total of 259 kidney biopsies with type I membranoproliferative glomerulonephritis (MPGN) were evaluated, and five grades of glomerular alterations were compared to the following four categories of tubulo-interstitial findings: no changes, interstitial fibrosis (IF), acute renal failure (ARF), ARF and IF combined. The tubulo-interstitial findings proved to be unrelated to the severity of the glomerular alterations. Severe glomerular lesions can be associated with completely normal interstitium and tubules. Conversely, low-grade glomerular lesions may be accompanied by severe tubular and/or interstitial lesions. When the renal cortical interstitium and tubules were normal, then creatinine and blood pressure values were within the normal range; however, these values were significantly elevated in the presence of IF and/or ARF. It is concluded from these findings that in MPGN type I the disturbance in the excretion function of the kidney is caused primarily by tubulo-interstitial changes rather than by glomerular lesions.


Quantification of Quercetin and Rutin from Benincasa hispida Seeds and Carissa Congesta Roots by High-performance Thin Layer Chromatography and High-performance Liquid Chromatography.
In Indian Ayurvedic system, Benincasa hispida (BH) and Carissa congesta (CC) are well-known plants used for major and minor ailments. BH has been regarded as Kushmanda, whereas CC has been used in immune-related disorders of the human system. Quercetin and rutin identified from the vast plethora of plant extracts have proved to possess ethnopharmacological relevance. In present studies, we have determined quercetin and rutin in terms of percentage in BH seeds and CC roots by high-performance thin layer chromatography (HPTLC) and high-performance liquid chromatography (HPLC). After extraction and phytochemical screening, the extracts were subjected to quantification for the presence of quercetin and rutin by HPTLC and HPLC. HPTLC showed quercetin as 44.60, 27.13% and rutin as 32.00, 36.31% w/w, whereas HPLC revealed quercetin as 34.00, 35.00% and rutin as 21.99, 45.03% w/v in BH and CC extracts, respectively. The BH and CC extracts have elucidated peaks that were corresponding with standard peaks on undertaking chromatographic studies. Quercetin and rutin are isolated from BH seeds and CC roots by High Performance. Thin Layer Chromatography and High Performance Liquid Chromatography. HPTLC revealed presence of quercetin as 44.60, 27.13 % and rutin as 32.00, 36.31 % w/w. HPLC revealed presence of quercetin as 34.00, 35.00 % and rutin as 21.99, 45.03 % w/v. Abbreviation Used: HPTLC: High Performance Thin Layer Chromatography; HPLC: High Pressure Liquid Chromatography, UV: Ultraviolet, CC: Carissa congesta, BH: Benincasa hispida.


The Effect of Triggering Receptor Expressed by Myeloid Cells 2 Modified Bone Marrow Mesenchymal Stem Cells on Alzheimer's Disease-Mouse Model.
This study aims to explore the effect of TREM2 modified BMSCs on hippocampus of AD mice. Mouse bone marrow mesenchymal stem cells were isolated and identified. APP/PS1 double transgenic mice were confirmed to be AD model and divided into 4 groups: control group, MSCs group, MSCs+vector group and MSCs+pEGFP-TREM2 group. The incubation period and the number of errors in the MSCs+pEGFP-TREM2 group were significantly decreased than that of control group after 3 days. The quantity and area of Aβ deposition in MSCs+pEGFP-TREM2 group were significantly smaller than that of control group. Aβ40 and Aβ42 levels were significantly decreased most in MSCs+pEGFP-TREM2 group. The expression levels of TREM2 and DAP12 significantly increased in the MSCs+pEGFP-TREM2 group. TREM2 modified bone marrow MSCs affected the ability of learning and memory of AD model mice and this mechanism may be related to the expression of TREM2 and DAP12 genes.


[Curettage plus cement reconstruction for treating giant cell tumor of limbs].
To evaluate curettage plus cement reconstruction in the treatment of giant cell tumor (GCT) of limbs. 125 patients with GCT of limbs were treated with curettage plus cement reconstruction. They were 62 men and 63 women aged from 12 to 71 years, 101 patients had primary GCT and 24 had recurrence of GCT. The recurrence at the knee was noted in 100 patients (80%). 125 patients were followed-up for 96 months (range 13 - 194 months). The recurrence rate was 12.7% in the primary group and 10.3% in the recurrent group. Two patients were infected. Joint functions were excellent. Curettage plus cement reconstruction is safe and effective in treating local GCT of limbs. The key the method is aggressive curettage of the lesion via a bone window. Cement is adjuvant therapy only.


The Impact of Sleep-Disordered Breathing on Severity of Pregnancy-Induced Hypertension and Feto-Maternal Outcomes.
There is a close association between sleep-disordered breathing (SDB) and preeclampsia. Both conditions have poor pregnancy outcomes. Forty women with new-onset hypertension of pregnancy and 60 age-matched normotensive pregnant women were subjected to polysomnography. The maternal and fetal outcomes of all the subjects were noted. SDB occurs more frequently (p = 0.018; OR 13.1) and with more severity (p 0.001; OR 1.8) in women with hypertensive disorders of pregnancy even after controlling for pre-pregnancy body mass index (BMI). Furthermore, the BMI significantly correlated with both the Apnea-Hypopnea Index (AHI; r = 0.745; p < 0.001) and the blood pressure (r = 0.617; p < 0.001) highlighting the contribution of obesity in the causation of hypertension and SDB. We also found a significant correlation between AHI and blood pressure even after adjustment for BMI pointing toward an independent role of SDB in the development of hypertension (r = 0.612; p = 0.01). Maternal and fetal complications significantly correlated with different parameters of SDB-AHI, Arousal Index and minimum oxygen saturation, in the cases and with the fetal complications in the controls as well. SDB occurs more frequently and with more severity in women with pregnancy-induced hypertension and is associated with more severe preeclampsia and adverse feto-maternal outcomes.


Using drug samples can hinder quality.
Some institutions prohibit the dispensing of drug samples. Once samples run out, patients must bear greater cost burden. Being provided samples creates prescribing habits among physicians.


[Estrogen induced rat model of uterine leiomyoma].
To establish an appropriate animal model of uterine leiomyoma and to understand the pathogenesis of this disease. Mature female rats were intramuscularly injected with estradiol benzoate at 200 μg or 300 μg twice a week. After injection for 8 or 10 weeks, the rats were sacrificed. We measured the serum levels of estrogen (E(2)) and progesterone (P), evaluated ER and PR expression, and calculated the leiomyoma forming rate and mortality of the rats. Histological changes were compared between rat uterine leiomyoma and human uterine leiomyoma with HE staining. The optimal dose and duration of E(2) for induction of uterine leiomyoma in rat were determined. In the rats treated with estradiol benzoate 200 μg for 8 weeks ìn the serum E(2) level increased significantly (P<0.01). Uterine nodules were visible in some of the tested rats. Based on the pathohistological Results , the uterine leiomyoma developed in the treated rats demonstrated similar features as in human uterine leiomyoma. The expressions of ER and PR were increased in the leiomyoma tissues. The rat model of uterine leiomyoma can be established by intramuscular injection of estradiol benzoate at 200 μg twice per week for 8 weeks, with similar features as those of human uterine leiomyoma. The high concentrations of ER and PR in uterine tissue might be related with the development of uterine leiomyoma in animal.


p53 shades of Hippo.
The three p53 family members, p53, p63 and p73, are structurally similar and share many biochemical activities. Yet, along with their common fundamental role in protecting genomic fidelity, each has acquired distinct functions related to diverse cell autonomous and non-autonomous processes. Similar to the p53 family, the Hippo signaling pathway impacts a multitude of cellular processes, spanning from cell cycle and metabolism to development and tumor suppression. The core Hippo module consists of the tumor-suppressive MST-LATS kinases and oncogenic transcriptional co-effectors YAP and TAZ. A wealth of accumulated data suggests a complex and delicate regulatory network connecting the p53 and Hippo pathways, in a highly context-specific manner. This generates multiple layers of interaction, ranging from interdependent and collaborative signaling to apparent antagonistic activity. Furthermore, genetic and epigenetic alterations can disrupt this homeostatic network, paving the way to genomic instability and cancer. This strengthens the need to better understand the nuances that control the molecular function of each component and the cross-talk between the different components. Here, we review interactions between the p53 and Hippo pathways within a subset of physiological contexts, focusing on normal stem cells and development, as well as regulation of apoptosis, senescence and metabolism in transformed cells.


Heavy metal migration and risk transference associated with cyanobacterial blooms in eutrophic freshwater.
The distribution of metals in cyanobloom-forming lakes, and potential risks of these metals during irrigation with water derived from the bloom were evaluated in this study. Seven metals were monitored throughout a cyanobacterial bloom season in Lake Taihu. Cyanobloom bio-dilution of the targeted metals could be explained by the negative relationships between total phytoplankton metal contents (Cu, Fe, Zn, Pb and Cr) and Chl a concentrations (p<0.05). Meanwhile, the ratios of extracellular bound to total cellular bound metals (Cu, Zn, Pb, Cr and Cd) were positively correlated with the ratios of cyanophyta to total phytoplankton (p<0.01), indicating the enhanced extracellular bound of these metals during cyanobloom period. Secondly, Cd, Pb and Cr were detected in several local vegetables. In comparison to reference vegetables, vegetables (e.g., radish, soybean, and cowpea), which were irrigated with cyanobloom broth collected from Lake Taihu, presented high health risk index (HRI) and were not safe for human consumption. Collectively, the frequent dominant colonial Microcystis blooms which performed high metal affinity might mediate the distribution of heavy metals in lake and potentially transferred these pollutants into terrestrial system.


Sensitive inexpensive chromatographic determination of an antimicrobial combination in human plasma and its pharmacokinetic application.
This study represents simple inexpensive chromatographic determination of ciprofloxacin (CIP) and tinidazole (TIN) simultaneously in human plasma using HPLC-DAD followed by a pharmacokinetic application. C18 column was used as stationary phase with isocratic elution of a mobile phase composed of acetic acid solution (2%) and acetonitrile (85: 15, v/v) and ornidazole as internal standard (IS) with UV detection at 318 nm. The two drugs and the IS were separated at 6.55, 7.91 and 11.07 min for CIP, TIN and IS, respectively, with good selectivity and sensitivity for their analysis in presence of plasma matrix components and the drugs' metabolites. Sample preparation involved only protein precipitation without any complicated extraction procedures decreasing analysis time. For method validation, FDA regulations for analysis in biological fluids were followed. Pharmacokinetic (PK) study on six healthy volunteers was conducted after single oral dose administration of 500 and 600 mg of CIP and TIN, respectively. Dugs' plasma levels were followed for 12 or 72 h post dosing for CIP and TIN, respectively, and different PK data for the two drugs were calculated and they were comparable to the reported values demonstrating successful future application of the presented method in PK, bioequivalence and bioavailability studies.


Scratching Beyond the Surface of Itchy Wounds.
In this issue of Immunity, Xu et al. reveal that dermal dendritic cells produce interleukin-31, which acts on neurons to promote wound itch. Their findings link itch associated with deeper wounds-wounds that extend beyond the epithelium-to the cells and cytokines that mediate wound healing.


Method for the sensitive analysis of individual molecular species of phosphatidylcholine by high-performance liquid chromatography using post-column fluorescence detection.
Conditions are described for the efficient resolution by reversed-phase high-performance liquid chromatography on octadecylsilica stationary phases of individual molecular species of phosphatidylcholine on the basis of their fatty acyl composition. The effects are described of varying stationary phase carbon loading, mobile phase polarity and column temperature. Eluted peaks were detected by a sensitive post-column fluorescence system using the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene. This detection system permitted direct quantitation of phosphatidylcholine species irrespective of the degree of acyl unsaturation and eliminated the need for elaborate pre-column derivatization. The techniques were applied to the analysis of phosphatidylcholine isolated from rat liver and lung.


A Transcriptional Network Promotes Anthocyanin Biosynthesis in Tomato Flesh.
Dietary anthocyanins are important health-promoting antioxidants that make a major contribution to the quality of fruits. It is intriguing that most tomato cultivars do not produce anthocyanins in fruit. However, the purple tomato variety Indigo Rose, which has the dominant Aft locus combined with the recessive atv locus from wild tomato species, exhibits light-dependent anthocyanin accumulation in the fruit skin. Here, we report that Aft encodes a functional anthocyanin activator named SlAN2-like, while atv encodes a nonfunctional version of the anthocyanin repressor SlMYBATV. The expression of SlAN2-like is responsive to light, and the functional SlAN2-like can activate the expression of both anthocyanin biosynthetic genes and their regulatory genes, suggesting that SlAN2-like acts as a master regulator in the activation of anthocyanin biosynthesis. We further showed that cultivated tomatoes contain nonfunctional alleles of SlAN2-like and therefore fail to produce anthocyanins. Consistently, expression of a functional SlAN2-like gene driven by the fruit-specific promoter in a tomato cultivar led to the activation of the entire anthocyanin biosynthesis pathway and high-level accumulation of anthocyanins in both the peel and flesh. Taken together, our study exemplifies that efficient engineering of complex metabolic pathways could be achieved through tissue-specific expression of master transcriptional regulators.


Diagnosis behind the mask: A rare case of infected Charcot's spine.
Charcot's spine is a very uncommon long-term complication of spinal cord injury. Infection of the spine is a common pathology, but infection of a Charcot's spine is rare and is challenging to diagnose, especially in differentiating between the Charcot defect and the osteomyelitis defect. Surgical reconstruction has to be extremely individualized. A 65-year-old man with a history of thoracic spinal cord injury with paraplegia 49 years ago was admitted to our hospital with high fever and aphasia. After a thorough diagnostic process, destructive Charcot's spine and secondary infection were diagnosed. This report additionally reviews the surgical management of secondary infected destructive lumbar Charcot's spine and follows the patient's recovery and postoperative quality of life.


Successful management of congenital bronchial stenosis using an expandable stent.
Congenital bronchial stenosis is a very rare cause of neonatal dyspnea. Surgical management remains challenging in small children. We report successful implantation of a bronchial stent in a 3-month-old female infant presenting with congenital right bronchial stenosis and 18 months of follow-up. Use of stents in children remains controversial because of the problem of size mismatch as the child grows. Nevertheless, expandable stent implantation could be an interesting alternative to complex surgery for localized bronchial stenosis in neonates.


Novel protein kinase C-beta isoform selective inhibitor JTT-010 ameliorates both hyper- and hypoalgesia in streptozotocin- induced diabetic rats.
Activation of protein kinase C (PKC) is thought to play an important role in the pathogenesis of diabetic microvascular complications. PKC-beta is elevated in hyperglycaemic conditions, both in vivo and in vitro. In this study, pharmacological effects of a novel PKC-beta isoform selective inhibitor, JTT-010 ((2R)-3-(2-aminomethyl-2,3-dihydro-1H-3a-azacyclopenta(a)inden-8-yl)-4-phenylaminopyrrole-2,5-dione monomethanesulphonate), on diabetic neuropathy were examined. PKC inhibitory activity of JTT-010 was evaluated with an enzyme assay. For the in vivo study, streptozotocin (STZ)-induced diabetic rats were treated with JTT-010 for 12 weeks and tail/sciatic nerve conduction velocity (NCV) evaluated. Hyper/hypoalgesia was evaluated using tail-flick and formalin tests. JTT-010 inhibited PKC-betaI and -betaII with IC50 values of 4.0 and 2.3 nm respectively. For other PKC isoforms, IC50 values were 54 nm or greater. In STZ-induced diabetic rats showing a reduction in tail/sciatic nerve conduction velocities, JTT-010 (0.3-3 mg/kg) ameliorated the reduction of these velocities. In a formalin test, STZ-induced diabetic rats had hyperalgesia in the first phase. JTT-010 reduced nociceptive response at doses of 0.1 mg/kg or higher. Furthermore, STZ-induced diabetic rats showed hypoalgesia in the second phase of the formalin test and tail-flick test. JTT-010 also ameliorates these symptoms at doses of 0.1 mg/kg or higher. These observations suggest that PKC-beta contributes not only to diabetic hyperalgesia, but also to hypoalgesia and also contributes to defects in NCV. PKC-beta inhibitor, JTT-010, may be beneficial in suppressing the development of diabetic nerve dysfunction, including hyperalgesia and hypoalgesia.


Managing Idiopathic Normal Pressure Hydrocephalus: Need for a Change of Mindset.
Idiopathic normal pressure hydrocephalus (iNPH) refers to a complex brain disorder characterized by ventricular enlargement and the classic Hakim's triad of gait and balance difficulties, urinary incontinence, and cognitive impairment. It predominantly affects older patients in the absence of an identified cause. As the elderly population continues to increase, iNPH becomes a growing concern in the complex spectrum of neuro-geriatric care, with significant socio-economic implications. However, unlike other well-structured management approaches for neurodegenerative disorders, the management of iNPH remains largely uncodified, leading to suboptimal care in many cases. In this article, we highlighted the challenges of current practice and identify key points for an optimal structuration of care for iNPH. Adopting a global approach to iNPH could facilitate a progressive shift in mindset, moving away from solely aiming to cure an isolated neurological disease with uncertain outcomes to providing comprehensive care that focuses on improving the daily life of frail patients with complex neurodegenerative burdens, using tailored goals.


Water quality improvement project for initial rainwater pollution and its performance evaluation.
Efficiently addressing initial rainwater pollution is crucial for mitigating urban water pollution. However, the performance evaluation of initial rainwater pollution control project is rarely introduced. In this study, the architecture of effective comprehensive engineering measures for improving the water quality of initial rainwater in Anhui Province, China, was described. Three water quality indicators, ammonia nitrogen (NH3-N), chemical oxygen demand (COD), and total phosphorus (TP), were selected to explore the severity of urban pollution caused by initial rainwater under various rainfall scenarios. A single-factor evaluation method was used to contrast and assess the benefits of the initial rainfall interception project in terms of water quality enhancement. Results showed that initial rainfall pollution was gentler under light rainfall conditions but more prominent under moderate and heavy conditions. The percentages of NH3-N, COD, and TP in Lotus Pond that met the tertiary drinking water standard were 100%, 74.91%, and 100% with great improvement, and the average concentrations of NH3-N, COD, and TP in Fushan Road Drainage have decreased by 91.43%, 10.49%, and 57.33% respectively, after the construction of the interception project. These indicated that the nitrogen and phosphorus pollution were successfully controlled by the control techniques in both locations, but COD concentration has to be addressed with more specialized strategies. Overall, the water quality improvement project for initial rainwater pollution plays a great role in effectively governing initial rainwater pollution and improving river water quality, and provides an effective technical reference for urban water ecological environment management.


The synthesis, mass spectrometric properties and identification of some N,N-di-(β-arylisopropyl)formamides related to the synthesis of ring-modified amphetamines.
This study examines the electron impact (EI) induced mass spectrometric behavior of several N,N-di-(β-arylisopropyl)formamides, which are connected to the Leuckart synthesis of some amphetamine analogues. Emphasis is laid on the fragmentation paths, which are common for all compounds under investigation and may be used in construction of the prediction scheme useful for identification of similar impurities, especially in absence of desirable authentic material. On the basis of this scheme several new N,N-di-(β-arylisopropyl)formamides have been identified in selected amphetamine analogues synthesized by the Leuckart method, including 4-methylthioamphetamine (4-MTA), 4-fluoroamphetamine (4-FA), 4-methylamphetamine, 3-trifluoromethylamphetamine, 3,4-methylenedioxyamphetamine (MDA), 2,5-dimethoxyamphetamine (2,5-DMA), 2,4,5- and 3,4,5-trimethoxyamphetamines (2-TMA and 3-TMA).


Inhibitory effects of orotate on precursor incorporation into nucleic acids.
The influence of orotic acid on the incorporation of precursors into nucleic acids was studied in mice and rats and in isolated cells. In vivo, orotate levels were modified by two diets which are known to increase the rate of pyrimidine nucleotide synthesis in rat liver. Of these diets, a 1% orotate diet had greater inhibitory effects than an arginine-deficient diet on the incorporation of [3H]orotate into RNA of mouse kidney than mouse liver. This contrasted with the situation in the rat where there was a greater effect in the liver than the kidney. The situation in the rat was more readily interpreted than in the mouse in terms of previously established effects of these diets on ribonucleotide pool sizes. However, studies using [3H]adenosine as a precursor for incorporation into RNA suggested that even in the mouse the effects of orotate were on pool sizes rather than an inhibitory effect on RNA synthesis. The incorporation of [3H]thymidine into DNA was inhibited by orotate to a similar degree in cultured HTC hepatoma cells and a line of rat liver epithelial cells. An effect on DNA synthesis rather than solely on pool sizes was suggested by the observation that the pool size of dTTP was not increased by 5 mM orotate under conditions in which there was a four-fold increase in the level of UTP in HTC cells. An inhibitory effect of orotate on DNA synthesis was further supported by an observation of decreased incorporation of [3H]deoxyadenosine into DNA and a lower rate of cellular proliferation.


Determination of the DNA-binding characteristics of ethidium bromide, proflavine, and cisplatin by flow injection analysis: usefulness in studies on antitumor drugs.
Flow injection analysis was used to study the reactions occurring between DNA and certain compounds that bind to its double helix, deforming this and even breaking it, such that some of them (e.g., cisplatin) are endowed with antitumoral activity. Use of this technique in the merging zones and stopped-flow modes afforded data on the binding parameters and the kinetic characteristics of the process. The first compound studied was ethidium bromide (EtdBr), used as a fluorescent marker because its fluorescence is enhanced when it binds to DNA. The DNA-EtdBr binding parameters, the apparent intrinsic binding constant (0.31+/-0.02 microM(-1)), and the maximum number of binding sites per nucleotide (0.327+/-0.009) were determined. The modification introduced in these parameters by the presence of proflavine (Prf), a classic competitive inhibitor of the binding of EtdBr to the DNA double helix, was also studied, determining the value of the intrinsic binding constant of Prf (K(Prf) = 0.119+/-9x10(-3) microM(-1)). Finally, we determined the binding parameters between DNA and EtdBr in the presence of the antitumor agent cisplatin, a noncompetitive inhibitor of such binding. This provided information about the binding mechanism as well as the duration and activity of the binding of the compound in its pharmacological use.


The design and use of specific genetic probes to identify closely related bunyaviruses and to determine the genotype of their recombinants.
Viruses that are very closely related to each other at the genetic and gene product level can prove difficult to distinguish, although they may differ in phenotype (for example in their virulence or vector preferences). A chimeric genetic probe has been developed and tested to distinguish the S RNAs of two closely related bunyaviruses, snowshoe hare and La Crosse viruses. The technique is applicable to other RNA species of these two bunyaviruses.


Recognition and Management of the Long-term Effects of Cranial Radiation.
Cranial radiation is ubiquitous in the treatment of primary malignant and benign brain tumors as well as brain metastases. Improvement in radiotherapy targeting and delivery has led to prolongation of survival outcomes. As long-term survivorship improves, we also focus on prevention of permanent side effects of radiation and mitigating the impact when they do occur. Such chronic treatment-related morbidity is a major concern with significant negative impact on patient's and caregiver's respective quality of life. The actual mechanisms responsible for radiation-induced brain injury remain incompletely understood. Multiple interventions have been introduced to potentially prevent, minimize, or reverse the cognitive deterioration. Hippocampal-sparing intensity modulated radiotherapy and memantine represent effective interventions to avoid damage to regions of adult neurogenesis. Radiation necrosis frequently develops in the high radiation dose region encompassing the tumor and surrounding normal tissue. The radiographic findings in addition to the clinical course of the patients' symptoms are taken into consideration to differentiate between tissue necrosis and tumor recurrence. Radiation-induced neuroendocrine dysfunction becomes more pronounced when the hypothalamo-pituitary (HP) axis is included in the radiation treatment field. Baseline and post-treatment evaluation of hormonal profile is warranted. Radiation-induced injury of the cataract and optic system can develop when these structures receive an amount of radiation that exceeds their tolerance. Special attention should always be paid to avoid irradiation of these sensitive structures, if possible, or minimize their dose to the lowest limit.


Organization of mixed dimethyldioctadecylammonium and choline modifiers on the surface of synthetic hectorite.
Understanding the nature of mixed surfactant self-assembly on the surface of organoclays is an important step toward optimizing their performance in polymer nanocomposites and for other potential applications, where selective surface interactions are crucial. In segmented thermoplastic polyurethane nanocomposite systems, dual-modified organoclays have shown significantly better performance compared to their single-modified counterparts. Until now, we had not fully characterized the physical chemistry of these dual-modified layered silicates, but had hypothesized that the enhanced composite performance arises due to some degree of nanoscale phase separation on the nanofiller surface, which enables enhanced compatibilization and more specific and inclusive interactions with the nanoscale hard and soft domains in these thermoplastic elastomers. This work examines the organization of quaternary alkyl ammonium compounds on the surface of Lucentite SWN using X-ray diffraction (XRD), thermogravimetric analysis (TGA), attenuated total reflectance Fourier-transfer infrared (ATR FT-IR), (13)C cross-polarization (CP)/magic angle spinning (MAS) nuclear magnetic resonance (NMR), and small-angle neutron scattering (SANS). When used in combination with choline, dimethyldioctadecylammonium (DMDO) was observed to self-assemble into discontinuous hydrophobic domains. The inner part of these hydrophobic domains was essentially unaffected by the choline (CC); however, surfactant intermixing was observed either at the periphery or throughout the choline-rich phase surrounding those domains.


Prediction of extensive necrotic change in acute gangrenous cholecystitis.
Gangrenous cholecystitis (GC) is a severe type of acute cholecystitis that implies higher mortality and morbidity rates than uncomplicated cholecystitis. The characteristics of GC are various for each case. However, preoperative predictors of GC with extensive necrotic change have not been investigated well. A total of 239 patients who were pathologically diagnosed with GC underwent laparoscopic cholecystectomy at our hospital between January 2013 and December 2021. Of these, 135 patients were included in this study and were subdivided into the extensive necrosis group (patients with necrotic change extending to the neck of the gallbladder, n = 18) and the control group (patients with necrotic change limited to the fundus or body, not extending to the neck, n = 117) according to each operation video. Patient characteristics and perioperative factors predicting extensive necrotic change were investigated. Pericholecystic fat stranding (83.3 vs. 53.8%, p = 0.018) and absence of wall enhancement on preoperative CT images (50.0 vs. 24.7%, p = 0.026) were significantly associated with extensive necrosis. Seven of 18 patients in the extensive necrosis group showed necrotic changes beyond the infundibulum. The absence of wall enhancement on preoperative CT images (71.4 vs. 28.8%, p = 0.018) was significantly associated with necrotic changes beyond the infundibulum. Pericholecystic fat stranding and absence of wall enhancement on preoperative enhanced CT are predictors of extensive necrotic change in patients with GC. In addition, the absence of wall enhancement also predicts the presence of necrotic changes beyond the infundibulum.


Breakthrough of hepatitis B virus escape mutants after vaccination and virus reactivation.
Escape mutants of hepatitis B virus (HBV) carry mutations in the major antigenic region of the hepatitis B surface antigen (HBsAg). They are able to grow in the presence of antibodies against HBsAg (anti-HBs) and may escape detection by immuno assays for HBsAg. Antibodies against HBV core antigen (anti-HBc) are considered to be a universal marker for active or resolved HBV infections but they may appear very late. Highly sensitive detection of HBV DNA is the most universal reliable marker of infectivity, but in the blood donation setting even the most sensitive assay for HBV DNA may not detect all infectious donations. This brief report describes three cases of HBV infections caused by HBV escape mutants. The implications of the findings for the prevention of HBV transmission through donor blood are discussed.


Stereoselective synthesis of bio-hybrid amphiphiles of coumarin derivatives by Ugi-Mannich triazole randomization using copper catalyzed alkyne azide click chemistry.
An efficient synthesis of ester-triazole-amide amphiphiles of coumarin derivatives by triazole randomization based on click approach is described. Twenty-five small peptide azides were synthesized using Ugi or alternate Mannich-type multi-component reactions. The new azides were then used for the triazole randomization of alkyne functionalized coumarin ester under CuAAC conditions. Sixty-five new peptide bio-hybrids are obtained in near quantitative yield with high regio and stereoselectivity.


The effects of high phenylalanine concentration on chick embryonic development.
Cells from a particular portion of the cranial neural crest (cardiac neural crest) migrate from the neural fold into pharyngeal arches 3, 4 and 6, where they provide the support for the endothelium of the aortic arch arteries, and by migration into the outflow tract become involved in septation of the truncus arteriosus. Ablation of the premigratory cardiac neural crest results in persistent truncus arteriosus and other defects reminiscent of the DiGeorge syndrome in man. Removal of a small area of the cardiac neural crest causes a spectrum of heart defects classified together as dextraposed aorta including changes like that of Fallot's tetralogy in man. Some inflow tract anomalies have also been found. Pilot studies injecting phenylalanine into developing chick embryos at a very early stage had little effect on embryo viability or on the incidence of congenital heart defects. However, sham-treated animals produced predominantly small simple ventricular septal defects but phenylalanine-treated embryos had more serious and complex heart anomalies. It is not possible to say yet that congenital heart disease in the offspring of mothers with untreated phenylketonuria is due to phenylalanine-induced damage to the neural crest, but the pilot studies in chick suggest that this idea is worth pursuing.


Small GTP-binding protein associated with Golgi cisternae.
Eukaryotic cells seem to use GTP hydrolysis to regulate vesicular traffic in exocytosis and endocytosis. The best evidence for this comes from studies on the yeast Saccharomyces cerevisiae that have identified two small Ras-related GTP-binding proteins, Sec4p and Ypt1p, which control distinct stages of the secretory pathway. In mammalian cells the effects of a non-hydrolysable GTP analogue, GTP-gamma S, on different transport events have suggested that they also have proteins functionally related to yeast Sec4p and Ypt1p. The rab genes have recently been cloned and sequenced for rat and human and their proteins have highly conserved domains in common with Sec4p and Ypt1p (including a putative effector binding site). They are therefore good candidates for GTP-binding proteins involved in intracellular transport in mammalian cells. One of the Rab proteins (Rab1p) is the mammalian counterpart of Ypt1p (ref. 13). Here we report the localization of the protein Rab6p to the Golgi apparatus in several cell types. By immunolabelling and electron microscopy, Rab6p appears to be concentrated predominantly on the medial and trans cisternae and distributed over their entire surface.


"Alternately divided" epidermal nevus of the fingers.
A 2-year-old white girl with divided (or kissing) epidermal nevus of the third and fourth fingers of the left hand is described. The possible pathogenesis of this unique lesion is also discussed.


The novel cyclopropapyrroloindole(CPI) bisalkylators bearing methoxycarbonyl and trifluoromethyl groups.
The novel 3-methoxycarbonyl-2-trifluoromethylcyclopropapyrroloindole (MCTFCPI) bisalkylators were synthesized and their antitumor activity was evaluated. Among these derivatives, 7f in which two MCTFCPI moieties are connected with a 5,5'-bis(2-carbonyl-1H-indole) group, was found to exhibit more prominent cytotoxicity and antitumor activity than U-77,779 (bizelesin) (2).


In vitro potential antioxidant activity of indigenous yeasts isolated from virgin olive oil.
The aim of the present study was to investigate the in vitro antioxidant activity of yeast strains isolated from virgin olive oil. The 2,2-diphenyl-1-picryl-hydrazyl (DPPH) free-radical scavenging activity of single cultures of 24 yeast strains belonging to eight species isolated from virgin olive oil was evaluated and compared with that of the reference yeast Saccharomyces boulardii. All the yeasts studied in vitro showed antioxidant activity similar to or superior to that of the reference yeast. The highest antioxidant activity was observed in Nakazawaea wickerhamii, which exceeded the value reached by the reference strain S. boulardii, while the significantly lowest values were observed in the Candida adriatica, Candida diddensiae and Barnettozyma californica strains. Tests performed with virgin olive oil enriched with Wickerhamomyces anomalus and S. boulardii yeast biomasses showed a positive correlation between the microbial biomass used and the percentage of antioxidant activity observed during 60 days of storage. Survival in virgin olive oil was also significantly higher for W. anomalus compared to S. boulardii. All the oil-borne yeasts studied showed DPPH free-radical scavenging activity in both aqueous and oily media. For the first time, the antioxidant activity of the microbiota of virgin olive oil is reported. This activity may indicate the probiotic characteristics of the microbiota.


Occlusion tool software for pulmonary vein occlusion verification in atrial fibrillation cryoballoon ablation.
Optimal pulmonary vein (PV) occlusion, usually verified with selective contrast injection, is mandatory to obtain an effective PV isolation during cryoballoon (CB) ablation. The purpose of this study was to verify the feasibility and the accuracy of a new dielectric sensing system in assessing PV occlusion during CB ablation in patients with atrial fibrillation (AF). We enrolled 28 consecutive patients with paroxysmal or persistent AF. After transseptal access, a detailed image reconstruction of left atrium and PVs was achieved with an octapolar or decapolar mapping catheter (Achieve catheter, Medtronic Inc.) and KODEX-EPD system (EPD Solutions, a Philips company). The degree of PV occlusion with the inflated Arctic Front Advance Cryoballoon (Medtronic Inc.) was verified using the new "occlusion tool" software module (EPD Solutions, a Philips company) and compared to an angiogram obtained with contrast medium injection in each PV. A total of 105 PV CB occlusion were tested. The new occlusion tool software module showed a 91% sensitivity and 76% specificity in assessing a complete PV occlusion verified with contrast medium injection. The positive predictive value was 80%, and the negative predictive value was 88.6%. Mean procedure time was 81 ± 17 minutes. Mean fluoroscopy time was 6 ± 2 minutes. No 30-day complications were observed. The new dielectric imaging system was able to assess the degree of PV occlusion during a CB ablation with good sensitivity and specificity.


Impact of provider volume on front-line chemotherapy guideline compliance and overall survival in elderly patients with advanced ovarian cancer.
We sought to evaluate whether provider volume or other factors are associated with chemotherapy guideline compliance in elderly patients with epithelial ovarian cancer (EOC). We queried the SEER-Medicare database for patients ≥66 years, diagnosed with FIGO stage II-IV EOC from 2004 to 2013 who underwent surgery and received chemotherapy within 7 months of diagnosis. We compared NCCN guideline compliance (6 cycles of platinum-based doublet) and chemotherapy-related toxicities across provider volume tertiles. Factors associated with guideline compliance and chemotherapy-related toxicities were assessed using logistic regression. Overall survival (OS) was compared across volume tertiles and Cox proportional-hazards model was created to adjust for case-mix. 1924 patients met inclusion criteria. The overall rate of guideline compliance was 70.3% with a significant association between provider volume and compliance (64.5% for low-volume, 72.2% for medium-volume, 71.7% for high-volume, p = .02). In the multivariate model, treatment by low-volume providers and patient age ≥ 80 years were independently associated with worse chemotherapy-guideline compliance. In the survival analysis, there was a significant difference in median OS across provider volume tertiles with median survival of 32.8 months (95%CI 29.6, 36.4) low-volume, 41.9 months (95%CI 37.5, 46.7) medium-volume, 42.1 months (95%CI 38.8, 44.2) high-volume providers, respectively (p < .01). After adjusting for case-mix, low-volume providers were independently associated with higher rates of mortality (aHR 1.25, 95%CI: 1.08, 1.43). In a modern cohort of elderly Medicare patients with advanced EOC, we found higher rates of non-compliant care and worse survival associated with treatment by low-volume Medicare providers. Urgent efforts are needed to address this volume-outcomes disparity.


FAP106 is an interaction hub for assembling microtubule inner proteins at the cilium inner junction.
Motility of pathogenic protozoa depends on flagella (synonymous with cilia) with axonemes containing nine doublet microtubules (DMTs) and two singlet microtubules. Microtubule inner proteins (MIPs) within DMTs influence axoneme stability and motility and provide lineage-specific adaptations, but individual MIP functions and assembly mechanisms are mostly unknown. Here, we show in the sleeping sickness parasite Trypanosoma brucei, that FAP106, a conserved MIP at the DMT inner junction, is required for trypanosome motility and functions as a critical interaction hub, directing assembly of several conserved and lineage-specific MIPs. We use comparative cryogenic electron tomography (cryoET) and quantitative proteomics to identify MIP candidates. Using RNAi knockdown together with fitting of AlphaFold models into cryoET maps, we demonstrate that one of these candidates, MC8, is a trypanosome-specific MIP required for parasite motility. Our work advances understanding of MIP assembly mechanisms and identifies lineage-specific motility proteins that are attractive targets to consider for therapeutic intervention.


Headache in the athlete and radiographic evaluation.
A deliberate attempt is made to stress the nonspecificity of headache and the complexity of its work-up. The choice of radiographic studies for its evaluation should be governed by the strongly considered etiology. This article deals with the most likely causes of headaches in an athlete. The merits and limitations of currently available radiographic modalities to detect headache-producing diseases are broadly discussed.


Robotic docking time with the Hugo™ RAS system in gynecologic surgery: a procedure independent learning curve using the cumulative summation analysis (CUSUM).
Robot-assisted surgery has been proven to offer improvements in term of surgical learning curve and feasibility of minimally invasive surgery, but has often been criticized for its longer operative times compared to conventional laparoscopy. Additional times can be split into time required for system set-up, robotic arms docking and calibration of robotic instruments; secondly, surgeon's learning curve. One of the newest systems recently launched on the market is the Hugo™ RAS (MEDTRONIC Inc, United States). As some of the earliest adopters of the Hugo™ RAS system technology, we present our data on robotic docking learning curve for the first 192 gynecologic robotic cases performed at our institution. Our data indicates that robotic set-up and docking with the new Hugo™ RAS robotic surgical system can be performed time-effectively and that the specific robotic docking learning curve is comparable to preexisting data for other platforms. This preliminary insights into this recently released system may be worthwhile for other centers which may soon adopt this new technology and may need some relevant information on topics such as OR times. Further studies are necessary to assess the different features of the Hugo™ RAS considering other technical and surgical aspects, to fully become familiar with this novel technology.


Structural attributes influencing unbound tissue distribution.
Unbound tissue-to-plasma partition coefficients (Kpuu) were determined for 56 structurally diverse compounds in rats following intravenous infusion. Five tissues were included in the study: white adipose, brain, heart, liver, and skeletal muscle. The rank ordering of the median tissue Kpuu values was: liver (4.5) > heart (1.8) > adipose (1.2) > skeletal muscle (0.6) > brain (0.05), with liver being most enriched and brain most impaired. The median Kpuu values of acids and zwitterions were lower than those of bases and neutrals in all tissues but liver. Selective tissue distribution was observed, dependent upon chemotype, which demonstrated the feasibility of targeting or restricting drug exposure in certain tissues through rational design. Physicochemical attributes for Kpuu were identified using recursive partitioning, which further classified compounds with enriched or impaired tissue distribution. The attributes identified provided valuable insight on design principles for asymmetric tissue distribution to improve efficacy or reduce toxicity.


Anatomy-oriented stereotactic approach to cerebrospinal fluid collection in mice.
Extraction of cerebrospinal fluid (CSF) in small animal models is an indispensable technique used in neuroscience and neuro-oncology research but can be technically challenging due to the small size of the brain. Here we describe a simple, reliable, and highly reproducible method for collecting CSF from anesthetized laboratory mice based on anatomical foundation, with no requirement of introducing any custom-made types of equipment. The mouse's head is fixed to a stereotaxic frame in the position that allows the maximum opening of the cisterna magna. A Hamilton syringe attached with a 26 gauge needle is inserted stereotactically in parallel to the brain axis to reach the cistern. The clear CSF (approximately 10 µl) can then be drawn slowly in approximately 5 min. Our modified approach minimizes technical variations that can result from customized equipment, and is applicable in broad research settings.


AbmR (Rv1265) is a novel transcription factor of Mycobacterium tuberculosis that regulates host cell association and expression of the non-coding small RNA Mcr11.
Gene regulatory networks used by Mycobacterium tuberculosis (Mtb) during infection include many genes of unknown function, confounding efforts to determine their roles in Mtb biology. Rv1265 encodes a conserved hypothetical protein that is expressed during infection and in response to elevated levels of cyclic AMP. Here, we report that Rv1265 is a novel auto-inhibitory ATP-binding transcription factor that upregulates expression of the small non-coding RNA Mcr11, and propose that Rv1265 be named ATP-binding mcr11 regulator (AbmR). AbmR directly and specifically bound DNA, as determined by electrophoretic mobility shift assays, and this DNA-binding activity was enhanced by AbmR's interaction with ATP. Genetic knockout of abmR in Mtb increased abmR promoter activity and eliminated growth phase-dependent increases in mcr11 expression during hypoxia. Mutagenesis identified arginine residues in the carboxy terminus that are critical for AbmR's DNA-binding activity and gene regulatory function. Limited similarity to other DNA- or ATP-binding domains suggests that AbmR belongs to a novel class of DNA- and ATP-binding proteins. AbmR was also found to form large organized structures in solution and facilitate the serum-dependent association of Mtb with human lung epithelial cells. These results indicate a potentially complex role for AbmR in Mtb biology.


Women and men with hip fractures have a longer femoral neck moment arm and greater impact load in a sideways fall.
In a case control study, we report that women and men with hip fractures have a longer moment arm of the force applied on the proximal femur during a sideways fall, a structural feature that may contribute to fracture risk. The impact load and its direction during a sideways fall onto the greater trochanter are partly determined by the geometry of the proximal femur. We hypothesized that the hip geometry in elderly with hip fractures produces a greater impact on the hip during a sideways fall. We studied 41 female (77.2 +/- 9.9 years) and 22 male (76.2 +/- 12.1 years) patients with hip fractures and 40 female (85.7 +/- 6.0 years) and 17 male (84.3 +/- 10.1 years) controls. Hip geometry was analyzed on the nonfracture hip in patients and left hip in controls using dual-energy X-ray absorptiometry. There was no difference in areal bone mineral density (aBMD), hip axis length, femoral neck axis length, or neck-shaft angle between cases and controls. However, the moment arm of the force on the hip during a sideways fall was 7.3% and 9.5% longer resulting in 5.6% and 9.1% greater moment in such a fall in female and male cases relative to their respective controls independent of height and weight (all p < 0.056). In multivariate logistic regression analysis, only the moment arm length in a sideways fall was associated with increased risk of hip fracture in females (odds ratio = 1.91, 95%CI: 1.14-3.20 for each SD increase in moment arm length of sideways fall, p = 0.02) and males (odds ratio = 2.69, 95% CI, 1.19-6.09, p = 0.01). A longer moment arm in the sideways fall increases the resultant force applied to the hip predisposing to hip fracture.


Transport of immune complexes from the subcapsular sinus into the lymph node follicles of the rat.
To study the mode of transport of immune complexes from the subcapsular sinus into the follicles of draining popliteal lymph nodes, horse radish peroxidase (HRP)-anti HRP was injected in rat footpads. Within six minutes, complexes were already present in the subcapsular sinus freely or attached to the plasma membrane of different types of cell including cells forming the stroma. A few minutes later, complexes were also seen in the deeper part of the outer cortex, and after two hours they had reached the periphery of the follicles. They were always seen scattered between lymphoid and non-lymphoid cells. After one day, complexes were present on well-developed follicular dendritic cells. After injection of HRP, no localization of this antigen was observed in the deeper part of the outer cortex including the follicles. These results strongly suggest that HRP-anti HRP complexes are passively transported through the outer cortex into the follicles where they are trapped and retained by follicular dendritic cells.


Caspase-3 activation and caspase-like proteolytic activity in human perinatal hypoxic-ischemic brain injury.
Human perinatal hypoxic-ischemic brain injury is an important cause of death and morbidity. One relatively common pattern of perinatal injury involves selective neuronal death in the ventral gray matter of the pons and in the subiculum of the hippocampal formation, classically termed 'pontosubicular neuronal necrosis' (PSN). The vulnerable neurons undergo karyorrhectic condensation of their nuclear chromatin and exhibit in situ end labeling for DNA fragmentation, leading to the recent reclassification of cell death in PSN as apoptotic. Caspase activation plays a central role in apoptosis and caspase-3 appears to be an especially important effector enzyme in neuronal apoptosis. In this study we performed immunohistochemistry on brain sections from six postmortem cases of PSN using two polyclonal antisera; CM1, a specific marker of caspase-3 activation, and fractin, which specifically recognizes a neoepitope at a caspase cleavage site in actin, and is therefore a marker of caspase-like proteolytic activity. Numerous CM1- and fractin-immunolabeled neurons were seen in the nuclei pontis and subiculum in each case, and the great majority showed karyorrhectic morphology. The immunostaining involved the nuclei and cytoplasm of these cells and the proximal portions at least of their neuritic processes. Some neurons exhibited a more extensive pattern of dendritic fractin labeling. Frequent CM1- and fractin-immunoreactive axonal segments were also seen. The identification of caspase-3 activation and caspase-like proteolytic activity in PSN cases in this study suggests that caspase inhibitors may potentially have a therapeutic neuroprotective role in human perinatal hypoxic-ischemic brain injury.


Ruptured middle cerebral aneurysm with accumulation of subarachnoid blood within convexity arachnoid cyst.
A case of acute rupture of a right middle cerebral bifurcation aneurysm with extravasation of blood into a distant arachnoid cyst is reported.


Early results of intersphincteric resection for patients with very low rectal cancer: an active approach to avoid a permanent colostomy.
Abdominoperineal resection has been the standard surgery for very low rectal cancer located within 5 cm of the anal verge. However, permanent colostomy exerts serious limitations on quality of life. The present study aimed to investigate curability and functional results of intersphincteric resection and additional partial external sphincteric resection for carcinoma of the anorectal junction. Thirty-five patients were prospectively studied from November 1999 to September 2002. All patients displayed adenocarcinoma (T3: n = 26; T2: n = 7; T1: n = 2) located between 0 and 2 cm above the dentate line. Abdominotransanal rectal resection with total mesorectal excision was performed in all patients (total intersphincteric resection: n = 14; subtotal intersphincteric resection: n = 5; additional partial external sphincteric resection: n = 6). All patients underwent diverting colostomy, which was closed at a median of six months postoperatively. Twenty patients received preoperative radiochemotherapy. All patients had curative intent with microscopic safety margins (mean surgical cut end: 4 mm; mean distal cut end: 10 mm). No postoperative mortality was encountered. Morbidity was identified in 13 patients (perianastomotic abscess: n = 4; anastomotic leakage and fistula: n = 4; postoperative bleeding: n = 2; wound infection: n = 1; anastomotic stenosis: n = 1; anovaginal fistula: n = 1). One of these patients received a permanent colostomy. Five patients developed recurrence (liver: n = 1; lung: n = 2; local and lung: n = 1; abdominal wall: n = 1) during the median observation period (23 months). Two of these patients underwent curative resection of liver or lung metastases. Twenty-one patients have received stoma closure, and although continence was satisfactory in all, 5 displayed occasional minor soiling 12 months after stoma closure. Anal canal manometry demonstrated significant reduction in maximum resting pressure (median: 50 cmH(2)O at 12 months after stoma closure), but acceptable function results were obtained. Curability and anal function were achieved by means of intersphincteric resection without or with additional partial external sphincteric resection. These procedures can be recommended for low rectal cancer patients who are candidates for abdominoperineal resection.


Demonstration of calcitonin gene-related peptide receptors in the gubernaculum by computerized densitometry.
The gubernaculum appears to guide inguinoscrotal testicular descent by migration into the scrotum ahead of the testis. Calcitonin gene-related peptide (CGRP) has been found in the scrotal branches of the genitofemoral nerve of neonatal rats, and is known to stimulate gubernacular motility in vitro. This study aimed to identify CGRP receptors in the gubernaculum, which should be present if CGRP mediates gubernacular migration toward the scrotum. Gubernacular sections from neonatal male rats were incubated with [125I]-human CGRP as well as a variety of unlabeled neuropeptides. By using computerized densitometry, the quantitation of CGRP binding derived from in vitro autoradiography demonstrated a distinctive distribution of binding sites for CGRP over the developing cremasteric muscle in the gubernaculum. The binding analysis showed a single class of sites with a dissociation constant (Kd) of 2.13 nmol/L and a receptor density of 27.4 fmol/mg polymer. These results endorse the hypothesis that CGRP released from the nerve acts directly on the cremaster via its own receptors, which have not been described previously.


Cross-cultural adaptation and validation of the geriatric 8 screening tool in Chinese hospitalized older adults with cancer.
To translate, cross-culturally adapt, and validate the Geriatric 8 (G8) questionnaire in Chinese hospitalized older adults with cancer. The Chinese version of the G8 (C-G8) was produced following Brislin's guidelines. The psychometric properties of the C-G8 were evaluated among 296 eligible patients. The content validity index of the C-G8 was 0.8∼1 at the item level and 0.975 at the scale level. The C-G8 identified more frail individuals among these older (>75 years) participants compared to their younger (65∼75 years) counterparts (frailty prevalence: 87.1% vs. 70.9%, P=0.010). The convergent validity of the C-G8 was tested by correlating it with the FRAIL scale (r=-0.592, P<0.001). The C-G8 had a lower internal consistency (Cronbach's α coefficient=0.501) but higher test-retest reliability and inter-rater reliability (intraclass correlation coefficient=0.913 and 0.993, respectively, P<0.001). The C-G8 questionnaire presented acceptable validity and reliability and could be used in Chinese hospitalized older adults with cancer.


Autobuttressing of colorectal anastomoses using a mesenteric flap.
Anastomotic leakage is a common and dreaded complication of colorectal surgery. Many different approaches have been tried to attempt to reduce leakage and associated morbidity. The concept of reinforcement of an anastomosis by buttressing is well established. Techniques described include using sutures, native omentum, animal or synthetic material. We report a technique for buttressing using a mesenteric flap to envelope the anastomosis. The primary rationale is to reduce clinical sequelae of anastomotic leakage by promoting local containment, as well as providing a scaffold for healing. Using autologous tissue provides a safe, time-efficient and cost-effective buttress without the risks of infection or reaction associated with foreign material. A mesenteric flap is particularly useful in patients in whom omentum is not available due to previous surgery, or to fill the dead space posterior to a low anastomosis within the pelvis.


4-PBA inhibits endoplasmic reticulum stress to improve autophagic flux in the treatment of protamine/lipopolysaccharide-induced interstitial cystitis in rats.
Interstitial cystitis (IC) has severe clinical symptoms with unclear mechanism. The continuous inflammatory response of the bladder is the basis of its pathogenesis. Endoplasmic reticulum stress (ERS) is involved in the regulation and development of various inflammatory diseases. And autophagy plays an important role in IC. In this study, we mainly focus on the therapeutic effect of endoplasmic reticulum stress and autophagy on protamine/lipopolysaccharide-induced interstitial cystitis. Female Sprague-Dawley rats were randomized into three experimental groups as follows: sham controls(N), IC alone, and IC+4-PBA.Rats in group IC received 10 mg/ml PS in the urinary bladder, followed by 2 mg/ml LPS instillation after 30 min, IC+4-PBA group SD rats received 4-PBA solution administered intragastrically once a day for 5 days. ERS biomarker (GRP78), autophagy-related proteins (LC3I/II, and Beclin1), autophagic flux biomarker (P62), inflammatory biomarkers (IL-6, TNF-a, NF-κB), apoptotic biomarkers (Caspase 3, Bax) were highest in the IC group compared to IC+4-PBA group and N group and the biomarkers expression in IC+4-PBA group were lower than in the IC group, anti-apoptotic biomarker (Bcl-2) was highest in the N group compared to the IC group and IC+4-PBA group and lower in the IC group than in the IC+4-PBA group, oxidative stress biomarkers (HO-1, NQO-1) were remarkably lower in the control group than in the IC and IC+4-PBA groups and notably lower in the IC group than in the IC+4-PBA group. The histological score and mast cell count demonstrated most severe in the IC group than those in the IC+4-PBA group. TUNEL assay examined the level of apoptosis in IC group was higher than in the IC+4-PBA group. The bladder micturition function was significantly improved with 4-PBA treatment. 4-PBA inhibits ERS to recover autophagic flux, and then to suppress the bladder oxidative stress, the inflammatory reaction and apoptosis, finally improve the bladder urinary function in Protamine/Lipopolysaccharide (PS/LPS) induced IC.


Tongue myokymia presenting twelve years after radiation therapy.
This case is a patient with tongue myokymia following radiation therapy 12 years earlier, documented using video and EMG. A 68-year-old woman with a history of nasopharyngeal carcinoma presented with subacute onset of difficulty in speaking and involuntary movements of her tongue approximately 12 years after radiation therapy to head and neck. Electromyography displayed myokymic discharges. There was no evidence of recurrent malignancy. Delayed effects of radiation therapy might be seen decades later. Myokymic discharges may reveal radiation-induced neuropathy.


Chest wall repair with a titanium instrument.
We performed chest wall repair with titanium alloy instruments as artificial ribs for prevention of paradoxical respiration and protection of the lung and liver after chest wall resection including the nearly entire length of the right seventh to the eleventh ribs and the costal arch for metastasis of osteosarcoma. The technique of this operation is presented diagrammatically.


Effects of stress and characteristic adaptability on semen quality in healthy men.
Semen from 28 healthy volunteers was assessed for basic semen measure and percent of abnormal morphologic forms every 2 weeks for 6 months. Concurrent self-reports were obtained on abstinence, frequency of ejaculation, health behavior and status, experienced stress, social support, and life events. A single assessment of characteristic adaptability (ego resiliency) also was obtained. Significant between-subject positive correlations were reported among selected semen measures, abstinence, and ego-resiliency. Stress was correlated negatively with semen measures of volume and percent normal morphologic forms.


Interspersed repetitive L1 family is differentially transcribed during the murine thymus ontogeny.
Repetitive L1 family in the first LINE (Long Interspersed Element) found in mammals. Structural and evolutionary studies demonstrated the capability of this family to play a functional role and several examples of L1 transcription have been reported in humans and mice especially in tumor cell lines.In this paper a general decrease in the L1 transcription level in different murine thymoma cell lines transformed by different means as compared to a normal counterpart represented by adult thymus is shown. When the same kind of analysis has been performed on normal thymus at different stages of differentiation (17th day embryos, new born, 30th day after birth) a modulated pattern of L1 transcription with a peak in the new born thymus was found. Furthermore, heterogeneous L1 transcription in all the above cases is demonstrated and its possible functional meaning discussed.


Removal of heavy metals by an enriched consortium.
An enriched consortium obtained from lake-sediment was developed for the removal of heavy metals such as Cu, Pb, Cr, Ni, and Zn from heavy metal-contaminated water. The removal efficiency of heavy metals in a shaking condition was generally higher than that in the static state. After the fifteenth enrichment with assorted heavy metals, the removal efficiencies in the shaking and static condition at an average concentration of 100 mg/L of each heavy metal were approximately 99 approximately 100% and 95 approximately 100%, respectively, depending on the type of heavy metal. An aerobically grown, pure culture isolated from an enriched culture was analyzed by 16S rRNA sequencing and identified as Ralstonia sp. HM-1. This strain was found to remove various heavy metals with an efficiency of approximately 97 approximately 100% at an average concentration of 200 mg/L of each heavy metal.


Changes in Bull Semen Metabolome in Relation to Cryopreservation and Fertility.
Semen cryopreservation determines several sperm damages, including the loss of fertility-associated proteins. The purpose of the study was to compare the metabolite contents in bovine sperm and seminal plasma before and after cryopreservation, and between high- and low-fertility bulls in vitro. Forty-eight ejaculates, collected from eight bulls (six per bull), were analyzed by liquid chromatography-mass spectrometry. Cryopreservation resulted in an over-expression of lysophosphatidylcholine (0:0/18:2(9Z,12Z)) in seminal plasma. In addition, higher levels of glycine betaine and pyro-l-glutaminyl-l-glutamine were observed in cryopreserved compared to fresh spermatozoa. The fresh seminal plasma of high-fertility bulls showed an over-expression of l-acetylcarnitine, glycerol tripropanoate, 2,3-diacetoxypropyl stearate and glycerophosphocholine, and an under-expression of lysophosphatidylcholine and butyrylcarnitine, compared to low-fertility bulls. Higher levels of glycerophosphocholine and lysophosphatidylcholine (16:0/0:0) were recorded in fresh spermatozoa from high-fertility bulls. In high-fertility bulls, a greater content of glycerophosphocholine and lower levels of butyrylcarnitine, glycine betaine and l-carnitine were found in cryopreserved seminal plasma, and lower levels of glycine betaine were detected in cryopreserved spermatozoa. In conclusion, cryopreservation affects bovine semen metabolome at both plasmatic and cellular compartments, and metabolic profile differs between high- and low-fertility bulls.


Administration of an antiprogesterone up-regulates estrogen receptors in the endometrium of women using Norplant: a pilot study.
To determine the effect of a single dose of mifepristone (200 mg) on endometrial estrogen and progesterone receptors in Norplant users. A prospective single-blind placebo-controlled pilot study. SETTING; Women were recruited from a large family planning clinic and were studied either at the clinic or in a clinical research unit attached to a teaching hospital gynecology department. Eight women using Norplant and experiencing vaginal bleeding more often than once every 24 days. All completed the study. Endometrial biopsies were taken after treatment with both placebo and 200 mg of mifepristone, both given at the start of a bleeding episode. Expression of endometrial progesterone (PR) and estrogen (ER) receptors, ovulation, and vaginal bleeding. Mifepristone administration was associated with down-regulation of PR receptor subtype B and up-regulation of ER. Women treated with mifepristone showed a tendency to increased ovulation rates and reduced vaginal bleeding. The effect of mifepristone on endometrial steroid receptors was consistent with functional inhibition of progesterone. The findings warrant further investigation of this regimen as a strategy to reduce frequent bleeding.


[Correlation and path analysis of artemisininum content and related factor on Artemisiae annie in Three Gorges reservoir area].
Study on the correlation and path analysis of artemisininum comtent and related factor on Artemisiae annie. In order to obtain high artemisininum content Artemisiae annie. On the natural condition, choose 36 area where Artemisiae annie growth in three gorges reservoir area. The related factor on artemisininum content are studies through correlation and path analysis. The artemisininum content had significant correlations with biomass, over cover degree, K, P, and N in soil. P in soil had the nost positive influence on the artemisininum content with the direct path coefficinent 0.3439, over cover degree had the nost negative in fluence on the artemisininum content with the direct path coefficient -0.1421. The influence order of other factor was N in soil (0.3180), K in soil (0.2352), biomass ( -0.0084), and plant height (-0.0347). Artemisininum content in Artemisiae annie leaves are correlated with biomass, over cover degree, K in soil, P in soil, N in soil.


Preservation of Solanum pimpinellifolium genomic fragments in recombinant genotypes improved the fruit quality of tomato.
Five recombinant inbred lines obtained from the F2 generation of an interspecific cross between cultivar, Caimanta (Cai, Solanum lycopersicum) and wild accession, LA722 (P, S. pimpinellifolium) were crossed to obtain the second cycle hybrids (SCH). Eleven fruit quality traits were assessed in evaluating phenotypic variability among genotypes P, Cai, F1 (Cai x P), five RILs, and 10 SCH. One of the five recombinant inbred lines and three SCH had higher values than P, as the best genotype for shelf life. Sequence-related amplified polymorphism was used as the molecular method for detecting polymorphism among these 18 genotypes. The percentage of polymorphism in RILs and SCH was 61% and 66% respectively. Moreover, some bands detected in P were present in SCH. Several multivariate analyses were performed to find agreement between the phenotypic variability observed for fruit quality traits and the polymorphism obtained from sequence-related amplified polymorphism markers. A general Procrustes analysis estimated that there was a consensus proportion of 75% between phenotypic and molecular data. There was considerable preservation of some bands from the wild genotype, which could increase the variability in fruit quality traits in populations where the genetic diversity is limited.