Characteristics of upper oesophageal sphincter and oesophageal body during maturation in healthy human neonates compared with adults.
We evaluated the upper oesophageal sphincter (UOS) relationship with oesophageal body during primary peristalsis (PP) sequences in healthy human neonates during maturation and compared with that of healthy adult volunteers. Forty-nine studies were performed using a water perfusion manometry system and a specially designed oesophageal catheter with a UOS sleeve concurrent with submental electromyogram in 31 subjects in supine position (18 preterm neonates, 29.9 +/- 2.5 weeks gestation; four full-term neonates, 39.3 +/- 1.0 weeks gestation; and nine adults, 18-65 years). The preterm neonates were studied longitudinally at 33 and 36 weeks postmenstrual age (PMA) and full-term born at 40 weeks PMA. Data were compared between the groups to recognize the effects of gestation, postnatal age and ageing. We evaluated 403 consecutive spontaneous solitary swallows during maturation (preterm at time-1 vs time-2) and growth (preterm and full-term vs adults) and observed significant (P < 0.05) differences in the basal UOS resting pressure, UOS relaxation characteristics, proximal and distal oesophageal body amplitude, duration, propagation and peristaltic velocity. Characteristics of UOS and PP are well-developed by 33 weeks PMA and undergo further maturation during the postnatal period, and are significantly different from that of adult.


Uterine leiomyomas with retroperitoneal lymph node involvement.
We have presented a case of benign metastasizing leiomyoma (BML) involving pelvic lymph nodes found at the time of hysterectomy for uterine leiomyomas. The patient received postoperative adjunctive therapy with methotrexate, actinomycin D, chlorambucil, and irradiation, and has no evidence of disease 11 years later.


Surgery of the abomasum.
Abomasal diseases are common in cattle. Many of these diseases can be managed surgically. This article briefly discusses the various classifications of abomasal diseases. It focuses on the surgical treatment of these diseases. Surgical principles of conventional surgery and minimally invasive techniques are discussed.


Increased nuclear localization of substance P in human gastric tumor cells.
Gastric cancer (GC) is an aggressive disease that remains the fourth most common type of cancer and is the second leading cause of cancer-related death worldwide. Treatment of advanced or metastatic GC has seen little progress and median overall survival in this group remains <1 year. It is urgent to investigate new mechanisms to understand GC progression. It is known that substance P (SP), after binding to the neurokinin-1 (NK-1) receptor, elicits GC proliferation; that GC cells and samples express NK-1 receptors; that NK-1 receptor antagonists, in a concentration dependent manner, inhibit the proliferation of GC cells and that these cells die by apoptosis. However, the presence of SP in GC and normal gastric cells is unknown. In order to know more on the involvement of the SP/NK-1 receptor system in GC, we studied in thirty human GC and normal gastric samples the immunolocalization of SP after using an immunohistochemical technique. SP was observed in the cytoplasm and in the nucleus of GC and normal gastric cells. The nuclear expression of SP was higher in GC cells than in normal cells. No significant difference was observed when the cytoplasmatic expression of SP in normal and GC cells was compared. The findings suggest that SP plays an important role in both nuclear function and GC.


An integrated risk assessment framework using information theory-based coupling methods for basin-scale water quality management: A case study in the Danjiangkou Reservoir Basin, China.
As the second largest reservoir in China, the Danjiangkou Reservoir (DJKR) serves as the water source of the Middle Route of the South-to-North Water Diversion Project of China (MRSNWDPC), i.e., the currently longest (1273 km) inter-basin water diversion project in the world, for more than eight years. The water quality status of the DJKR basin has been receiving worldwide attention because it is related to the health and safety of >100 million people and the integrity of an ecosystem covering >92,500 km2. In this study, basin-scale water quality sampling campaigns were conducted monthly at 47 monitoring sites in river systems of the DJKRB from the year 2020 to 2022, covering nine water quality indicators, i.e., water temperature (WT), pH, dissolved oxygen (DO), permanganate index (CODMn), five-day biochemical oxygen demand (BOD5), ammonia nitrogen (NH3-N), total phosphorus (TP), total nitrogen (TN), and fluoride (F-). The water quality index (WQI) and multivariate statistical techniques were introduced to comprehensively evaluate water quality status and understand the corresponding driving factors of water quality variations. An integrated risk assessment framework simultaneously considered intra and inter-regional factors using information theory-based and the SPA (Set-Pair Analysis) methods were proposed for basin-scale water quality management. The results showed that the water quality of the DJKR and its tributaries stably maintained a "good" status, with all the average WQIs >60 of river systems during the monitoring period. The spatial variations of all WQIs in the basin showed significantly different (Kruskal-Wallis tests, P < 0.01), while no seasonal differences were found. The increase in built-up land use and agricultural water consumption revealed the highest contributions (Mantel's r > 0.5, P < 0.05) to the rise of nutrient loadings of all river systems, showing the intensive anthropogenic activities can eclipse the power of natural processes on water quality variations to some extent. The risks of specific sub-basins that may cause water quality degradation on the MRSNWDPC were effectively quantified and identified into five classifications based on transfer entropy and the SPA methods. This study provides an informative risk assessment framework that was relatively easy to be applied by professionals and non-experts for basin-scale water quality management, thus providing a valuable and reliable reference for the administrative department to conduct effective pollution control in the future.


Relationships between health literacy and heart failure knowledge, self-efficacy, and self-care adherence.
It has been argued that only 12% of adults have the necessary health literacy to manage their health care effectively, which can lead to difficulties in self-care activities, such as medication adherence. Prior research suggests that health literacy may influence knowledge, self-efficacy and self-care, but this has not been fully examined. To test a model to explain the relationships between health literacy, heart failure knowledge, self-efficacy, and self-care. Prior to receiving clinic-based education, newly referred patients to 3 heart failure clinics completed assessments of health literacy, heart failure knowledge, self-efficacy, self-care, and demographics. Structural equation modeling was completed to examine the strength of the inter-variable relationships. Of 81 participants recruited, data from 63 patients were complete. Health literacy was independently associated with knowledge (P < 0.001). Health literacy was not related to self-care. Self-efficacy was independently-associated with self-care adherence (P = 0.016). No other relationships were statistically significant. The model had good fit (comparative fit index = 1.000) and explained 33.6% of the variance in knowledge and 27.6% in self-care. Health literacy influences knowledge about heart failure but not self-care adherence. Instead, self-efficacy influenced self-care adherence. Future research should incorporate additional factors that may better model the relationships between health literacy, knowledge, self-efficacy, and self-care.


Towards a method for determining age ranges from faces of juveniles on photographs.
The steady increase in the distribution of juvenile pornographic material in recent years strongly required valid methods for estimating the age of the victims. At the present in fact forensic experts still commonly use the assessment of sexual characteristics by Tanner staging, although they have proven to be too subjective and deceiving for age estimation. The objective of this study, inspired by a previous EU project involving Italy, Germany and Lithuania, is to verify the applicability of certain anthropometric indices of faces in order to determine age and to create a database of facial measurements on a population of children in order to improve face ageing techniques. In this study, 1924 standardized facial images in frontal view and 1921 in lateral view of individuals from 7 age groups (3-5 years, 6-8 years, 9-11 years, 12-14 years, 15-17 years, 18-20 years, 21-24 years) underwent metric analysis. Individuals were all of Caucasoid ancestry and Italian nationality. Eighteen anthropometric indices in the frontal view and five in the lateral view were then calculated from the obtained measurements. Indices showing a correlation with age were ch-ch/ex-ex, ch-ch/pu-pu, en-en/ch-ch and se-sto/ex-ex in the frontal view, se-prn/se-sn, se-prn/se-sto and se-sn/se-sto in the lateral view. All the indices increased with age except for en-en/ch-ch, without relevant differences between males and females. These results provide an interesting starting point not only for placing a photographed face in an age range but also for refining the techniques of face ageing and personal identification.


Brain-derived neurotrophic factor expression in the substantia nigra does not change after lesions of dopaminergic neurons.
Progressive and irreversible loss of specific neuronal cell populations is commonly seen in chronic neurodegenerative diseases such as Parkinson's disease (PD). Evidence is accumulating that apoptosis is a crucial cellular event responsible for the dysfunction and death of neurons in this disease. Thus, limiting apoptosis may prevent disease pathogenesis. Key to reducing apoptosis is the discovery of neuroprotective compounds that can be given to patients to minimize neuronal damage. In this manuscript, we reviewed the rationale of using an experimental strategy to provide neurotrophic support to injured neurons. Such rationale includes the increase of endogenous production of brain-derived neurotrophic factor (BDNF). BDNF is a potent inhibitor of apoptosis-mediated cell death and neurotoxin-induced degeneration of dopaminergic neurons. However, availability of BDNF may be reduced when dopaminergic neurons degenerate. Therefore, in this work, we have used several well-established neurotoxins for dopaminergic neurons, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, 6-OH-dopamine (6-OHDA), and the HIV protein gp120, to examine whether degeneration of nigrostriatal fibers alters BDNF expression. Our data show that these neurotoxins do not decrease the levels of BDNF in the substantia nigra, suggesting that up-regulation of BDNF synthesis by pharmacological means may be a viable therapy to slow down the progress of PD and other neurodegenerative diseases.


Double network hydrogel based on curdlan and flaxseed gum with photothermal antibacterial properties for accelerating infectious wound healing.
The healing of infected wounds has always been a clinical challenge. With the increasing threat of drug resistance due to antibiotic overuse, it is imperative to improve antibacterial wound dressings. In this study, we designed a double network (DN) hydrogel via a "one pot method" with antibacterial activity, and natural polysaccharides with the potential to promote skin wound healing were used. That is, a DN hydrogel matrix was formed by the hydrogen bond crosslinking of curdlan and the covalent crosslinking of flaxseed gum under the action of borax. We added ε-polylysine (ε-PL) as a bactericide. Tannic acid/ferric ion (TA/Fe3+) complex was also introduced into the hydrogel network as a photothermal agent to induce photothermal antibacterial properties. The hydrogel had fast self-healing, tissue adhesion, mechanical stability, good cell compatibility and photothermal antibacterial activity. In vitro studies of hydrogel showed its ability to inhibit S. aureus and E. coli. In vivo experiments also demonstrated the significant healing effect of hydrogel when used to treat wounds infected by S. aureus by promoting collagen deposition and accelerating the formation of skin appendage. This work provides a new design for the preparation of safe antibacterial hydrogel wound dressings and demonstrates great potential for promoting wound healing of bacterial infections.


Coir fiber as thermal insulator and its performance as reinforcing material in biocomposite production.
Coir is a lignocellulosic natural fiber derived from the coconut's husk, an abundantly found fruit or nut worldwide. This fiber has some unique characteristics, such as its resistance to seawater, microbial attack, high impact, etc. But its low thermal conductivity or high thermal insulating property makes it suitable for being used as insulators in civil engineering sites. On the other hand, the sustainability of a material depends heavily on its environmental impact of the material. For making sustainable materials like biocomposite, there are no options other than using polymers derived from natural renewable sources. Polylactic acid(PLA) is an example of those types of material. And these materials are often being reinforced by fibers like coir for various reasons including improving mechanical properties, reducing the cost of the material, and improving the material's sustainability. Many coir-reinforced sustainable biopolymer composites have already been produced in many pieces of research, which will be discussed in this paper, along with the chemical and physical structure of coir fiber. In addition, this paper will try to focus on the insulating properties of coir and coir-reinforced composites while will also compare some properties of the composites with some commonly used materials based on different parameters to show the suitability of using the coir fiber in heat-insulating applications and to produce sustainable biocomposite materials.


The activation of nitric oxide synthase by copper ion is mediated by intracellular Ca2+ mobilization in human pulmonary arterial endothelial cells.
The aim of the study was to elucidate the vasodilatory mechanism due to Cu2+ by assessing nitric oxide (NO) production as determined by NOx (NO, NO2-, and NO3-) that is released from human pulmonary arterial endothelial cell (HPAEC) monolayers using a NO chemiluminescence analyzer, and also to assess Ca2+ movement using 45Ca and fura 2 in HPAEC. Cu2+ (10(-6)-10(-4) M) significantly increased NO production in a dose-dependent manner when extracellular Ca2+ was present. 45Ca influx into the adherent cells was dose-dependently enhanced by Cu(2+) (10(-6)-10(-4) M), but not by Mn(2+), Zn(2+) or Fe(2+). [Ca2+]i, measured by monitoring the fluorescence changes of fura 2, was significantly elevated in the presence of Cu2+. The increase in [Ca2+]i induced by Cu2+ was inhibited by either diethyldithiocarbamate (DDC) or the depletion of extracellular Ca2+. The dihydropyridine receptor agonist, BayK8644, significantly attenuated the Cu2+-induced increase in [Ca2+]i in a dose dependent manner and nitrendipine or nifedipine, the dihydropyridine receptor antagonists, dose-dependently inhibited a Cu2+-induced increase in [Ca2+]i. These results suggest that Cu2+ activates eNOS through the mechanism of [Ca2+]i elevation due to Ca2+ influx into HPAEC and that the Cu2+-induced [Ca2+]i elevation in HPAEC is likely due to activation of the dihydropyridine-like receptors.


Shear Bond Strength of Different Restorative Materials to Primary Tooth Dentin Treated with Silver Diamine Fluoride.
Purpose: To investigate shear bond strength (SBS) of three restorative materials on primary dentin after silver diamine fluoride (SDF) application.
Methods: Thirty primary teeth were randomized into three groups of 10 teeth. Each tooth was split mesiodistally and randomized into experimental (artificial caries plus SDF) and control (sound dentine without SDF) groups. Glass ionomer cement (GIC), resin-modified bioactive resin (ACTIVA), and composite resin (CR) restorations were tested for SBS and mode of failure (MF).
 Results: All SDF groups exhibited significantly lower SBS compared to the control (CR: P =0.001; ACTIVA: P =0.001; GIC: P =0.004). For the SDF group, the compa- rison of materials was statistically significant (P =0.006); posthoc tests showed significance only between CR and ACTIVA (P =0.009) and between ACTIVA and GIC (P =0.020). The lowest mean value was obtained for ACTIVA (1.4 MPa) and the highest mean value was obtained for CR (3.3 MPa). For the control group, Welch's F test was statistically significant (P =0.044), but all posthoc tests were not. For MF, SDF exhibited a significantly greater percentage of adhesive failures with ACTIVA and CR than with GIC. In the control group, a mixed MF was more dominant with no significant differences.
Conclusion : The SDF group had significantly lower SBS.


Sphincteroplasty in the treatment of biliary tract disease. A prospective study of 46 cases.
Forty-six patients in whom sphincteroplasty was performed by an original technique are presented. In 43 cases the indication was oddian stenosis (associated or not with cholelithiasis or hepatic hydatid disease). Only in three patients a "security" operation was performed. Sphincteroplasty was achieved with the aid of an original probe, and average length of the incision of the ampullary area was 27 mm. The postoperative control, made by tube cholangiography and barium investigation, has evidenced the presence of a wide, open choledochoduodenal aperture. Amylase activity was also followed up in 25 patients. One case of acute pancreatitis, two upper digestive haemorrhages and one case of duodenal fistula were recorded as postoperative complications. Healing was obtained in all patients.


Suspected environmental poisoning by drugs, household products and pesticides in domestic animals.
Animal poisoning by chemicals (pesticides and household products) and drugs is a frequent occurrence and special attention should be paid to this phenomenon to improve prevention and treatment strategies and because of the fundamental role that animals may play as bioindicators. From January 2017 to March 2019 the Poison Control Centre of Milan (CAV) in collaboration with the University of Milan, collected and analyzed epidemiological data on animal poisoning. During this period, the CAV received a total of 442 enquiries on domestic animal poisoning episodes and, among these, 80.3 % were related to chemicals and drugs. Pesticides and drugs were the two major causes of poisoning (34.1 % and 33.5 %, respectively), followed by household products (29.3 %) and other causative agents (3.1 %, n = 11). In conclusion, these findings can provide useful information for the identification and monitoring of known and emerging toxicants, with positive repercussions on human, animal and environmental health.


Chemiluminescence in the presence of ferritin.
The ability of ferritins with differing iron contents to catalyze the oxidation of luminol by hydrogen peroxide was studied. The least efficient catalysts were iron-rich ferritins, and the most potent were those with iron to protein ratios of less than 0.1.


PTBP3 promotes tumorigenesis of glioblastoma by stabilizing Twist1.
Glioblastoma (GBM) is the most common malignancy tumor of central nervous system. PTBP3 was closely associated with the development of tumor. However, the function and molecular mechanism of PTBP3 in GBM is little known. qPCR and immunoblotting were used to detect PTBP3 expression levels in glioma tissues and cells. CCK8, Edu, flow cytometry, wound healing, and transwell assays were used to examined the function of PTBP3 in GBM. qPCR, Immunoblotting, and ubiquitination assays were performed to identify the mechanism of PTBP3. We found that PTBP3 was upregulated in GBM, and high expression of PTBP3 correlated with the poor survival of GBM patients. PTBP3 knockdown reduced proliferation, invasion, and migration of GBM. Conversely, overexpressing PTBP3 has an opposite effect. Moreover, PTBP3 had an effect on the EMT of GBM. More importantly, we found that PTBP3 stabilized Twist1 by decreasing its ubiquitination and degradation. Furthermore, orthotopic xenograft models were used to demonstrate the PTBP3 on the development of GBM in vivo. This study proved that PTBP3 promoted tumorigenesis of GBM by stabilizing Twist1, which provided a new therapeutic target for GBM.


Accessory cell-derived helper signals in human T-cell activation with phytohemagglutinin: induction of interleukin 2-responsiveness by interleukin 6, and production of interleukin 2 by interleukin 1 [corrected].
Interleukins (IL-) 1 and 6 have been shown to represent accessory signals for T-cell activation. In the present study, we further examined the effects of both cytokines on accessory cell-depleted human T cells stimulated with phytohemagglutinin (PHA). The addition of IL-6 to the cultures resulted in T-cell proliferation; however, IL-1 was unable to support PHA-induced T-cell growth. The addition of IL-1 consistently induced a low level of IL-2 production and strongly enhanced T-cell proliferation in the presence of IL-6. Thus, the effect of IL-1 on T-cell growth becomes apparent only in the presence of IL-6. Blocking the IL-2-receptor (IL-2R) with the monoclonal antibodies anti-Tac and MikBêta 1 (directed to the alpha and bêta chains of the IL-2R, respectively) had no effect on PHA/IL-6-supported proliferation, but completely eliminated the growth-enhancing effect of IL-1. On the other hand, a neutralizing anti-IL-4-antiserum did not affect PHA/IL-6- or PHA/IL-6/IL-1-induced proliferation. Further experiments showed that IL-6 enhances T-cell responsiveness to IL-2, as evidenced by enhanced IL-2-induced proliferation. However, we could not find an effect of IL-6 on the expression of IL-2R as measured by staining with anti-Tac and with MikBêta 1 or by binding of (125I)-IL-2 to T cells. It can be concluded from these studies that IL-1 and IL-6 have different helper effects on PHA-induced T-cell activation. In the presence of PHA, IL-6 induces limited IL-2/IL-4-independent growth, and more importantly it renders T cells responsive to IL-2. IL-1 provides a signal leading to IL-2 production. The combination of IL-1 and IL-6 represents a synergistic helper signal, leading to an IL-2-dependent pathway of proliferation.


Appraisal of the MTT assay as a rapid test of chemosensitivity in acute myeloid leukaemia.
We describe the application of a simple, rapid, semi-automated assay to the sensitivity testing of cytotoxic drugs in 23 patients with acute myeloid leukaemia (AML). The survival of blast cells from the bone marrow was measured by the MTT assay after 48 h continuous exposure to drugs both singly and in combination. There was a linear relationship between the number of leukaemic cells and the optical density of the formazan produced. The assay demonstrated a variation in drug sensitivity between patients. The technique was reproducible and there was no significant difference in response between blast cells obtained from bone marrow or from peripheral blood. Preliminary results show a correlation between in vitro and in vivo data. The test can be repeated throughout the course of the disease to help identify any change in tumour sensitivity. This technique appears to give useful information to assist in the management of acute myeloid leukaemia.


The diurnal pattern of protein synthesis in human skeletal muscle.
The diurnal pattern of protein synthesis in skeletal muscle was studied in relation to the serum concentrations of glucose, insulin and cortisol. Twelve healthy volunteers were given an ordinary hospital diet at 4-hourly intervals. The concentration of insulin showed peaks in response to food intake, and that of cortisol decreased over the day. Muscle biopsies were taken 30 min before the first food intake and 1.5 or 3.5 h after a meal. Irrespective of the time intervals after food intake, the total ribosome concentration, percentage amount of polyribosomes and polyribosome concentrations remained unaltered, indicating that there were no alterations in the capacity for protein synthesis accompanying the feeding schedule. The results suggest that a muscle sample taken in the morning after an overnight fast is representative of the protein synthesis during the day as assessed by the ribosome concentration and the size distribution of ribosomes.


Anatomic considerations in evaluation of the proximal ulnar nerve.
Knowledge of general ulnar anatomy aids in the understanding of the possible site of ulnar nerve entrapment and the rationale for differential diagnosis possibilities. Understanding of internal nerve topography sheds light on reasons for ulnar nerve susceptibility at the elbow region and offers an explanation for the sparing of forearm muscles in ulnar neuropathy at the elbow. Dynamic anatomy or biomechanics of the elbow help elucidate the pathophysiology of ulnar nerve compression at the elbow. The anatomy interface with electrodiagnosis illustrates rationale for particular methods employed and particular tests used in evaluating the ulnar nerve. Electrodiagnostic testing enhances localization of ulnar nerve lesions, excludes other causes in the differential diagnosis, and may aid with surgical selection.


Retrospective Evaluation of Immediate Impacted Third Molars Autotransplantation After Extractions of Mandibular First and/or Second Molars With Chronic Periapical Lesions.
To evaluate the success rate of simultaneous autotransplantation of the immature impacted third molars with the guidance of computer-aided rapid prototyping (CARP) to the place of mandibular first or second molars with extraction indication due to the untreatable radiographic periapical lesions. Twelve radiographically and clinically hopeless mandibular first or second molars with periapical lesions of 10 patients between the ages of 15 to 21 were included in this retrospective clinical study. Cone-beam computed tomography (CBCT) images were used to produce the CARP models of the donor impacted third molars. Following the extractions of the mandibular first or second molars with periapical lesions, sockets were curetted and prepared with proper burs until a suitable infraocclusal fit of the CARP models. The donor teeth were transplanted synchronously with their surgical extractions. Postoperatively patients were followed clinically and radiographically in the 3rd and 6th months and every 6th month thereafter for at least 18 months. Clinically, the mobility, periodontal plaque, bleeding on probing, percussion sensitivity, periodontal pocket, vitality, and occlusion, and radiographically, the root resorption, ankylosis, presence of lamina dura, and healing of periapical lesion were assessed. By the end of 12th month, and thereafter, all transplanted teeth were in occlusion and functioning properly with no clinical or radiological signs of pathology. All of the autotransplantation cases involved in this clinical study were successful within a mean follow-up period of 20.4 months with the least one of 18 months. Immediate autotransplantation of the immature third molars to the place of mandibular first or second molars with extraction indication due to the periapical lesion can be a proper treatment option for adolescent patients.


Prediction of adverse health outcomes using an electronic frailty index among nonfrail and prefrail community elders.
Early recognition of older people at risk of undesirable clinical outcomes is vital in preventing future disabling conditions. Here, we report the prognostic performance of an electronic frailty index (eFI) in comparison with traditional tools among nonfrail and prefrail community-dwelling older adults. The study is to investigate the predictive utility of a deficit-accumulation eFI in community elders without overt frailty. Participants aged 65-80 years with a Clinical Frailty Scale of 1-3 points were recruited and followed for 2 years. The eFI score and Fried's frailty scale were determined by using a semiautomated platform of self-reported questionnaires and objective measurements which yielded cumulative deficits and physical phenotypes from 80 items of risk variables. Kaplan-Meier method and Cox proportional hazards regression were used to analyze the severity of frailty in relation to adverse outcomes of falls, emergency room (ER) visits and hospitalizations during 2 years' follow-up. A total of 427 older adults were evaluated and dichotomized by the median FI score. Two hundred and sixty (60.9%) and 167 (39.1%) elders were stratified into the low- (eFI ≤ 0.075) and the high-risk (eFI > 0.075) groups, respectively. During the follow-up, 77 (47.0%) individuals developed adverse events in the high-risk group, compared with 79 (30.5%) in the low-risk group (x2, p = 0.0006). In multivariable models adjusted for age and sex, the increased risk of all three events combined in the high- vs. low-risk group remained significant (adjusted hazard ratio (aHR) = 3.08, 95% confidence interval (CI): 1.87-5.07). For individual adverse event, the aHRs were 2.20 (CI: 1.44-3.36) for falls; 1.67 (CI: 1.03-2.70) for ER visits; and 2.84 (CI: 1.73-4.67) for hospitalizations. Compared with the traditional tools, the eFI stratification (high- vs. low-risk) showed better predictive performance than either CFS rating (managing well vs. fit to very fit; not discriminative in hospitalizations) or Fried's scale (prefrail to frail vs. nonfrail; not discriminative in ER visits). The eFI system is a useful frailty tool which effectively predicts the risk of adverse healthcare outcomes in nonfrail and/or prefrail older adults over a period of 2 years.


Determination of Neisseria gonorrhoeae susceptibility to ciprofloxacin in clinical specimens from men using a real-time PCR assay.
A real-time PCR (RT-PCR) assay was modified to simultaneously detect Neisseria gonorrhoeae and to determine gonococcal susceptibility to ciprofloxacin using clinical samples. The modified RT-PCR assay was validated using DNA extracted from 40 linked isolates and urethral swabs, 24 of which had linked first-pass urine samples, obtained from men presenting with urethral gonorrhoea. The RT-PCR assay enabled amplification of N. gonorrhoeae dcmH, gyrA and parC genes. The quinolone resistance-determining regions (QRDRs) of the isolates' gyrA and parC genes were sequenced. Following successful validation, 33 first-pass urine-derived DNA extracts, obtained from men with gonorrhoea, were tested with the assay and results were compared with blinded ciprofloxacin susceptibility data. Gonococcal susceptibility to ciprofloxacin correlated perfectly with gyrA amplicon generation. No gyrA amplicons were detected for gonococcal infections due to ciprofloxacin-intermediate/resistant organisms. Amplification of parC correlated less well with ciprofloxacin susceptibility phenotypes. Simultaneous non-generation of gyrA and parC amplicons consistently predicted the presence of ciprofloxacin-resistant gonococci. Characteristic point mutations in the gyrA/parC QRDRs were found in DNA amplified from those extracts that failed to produce gyrA/parC amplicons. The RT-PCR assay performed well with DNA extracted from first-pass urine specimens and results correlated perfectly with ciprofloxacin susceptibility phenotypes. In conclusion, the modified RT-PCR assay can detect N. gonorrhoeae in DNA extracted from first-pass urine specimens of men with urethral gonorrhoea and accurately predicts gonococcal susceptibility to ciprofloxacin. This molecular assay provides a useful tool for surveillance and patient management in settings where fluoroquinolones can still be used for treatment of gonorrhoea.


Myxedema coma and inappropriate antidiuretic hormone secretion after deep neck irradiation: clinical implications and report of a case.
A case report is presented in which myxedema coma and inappropriate antidiuretic hormone secretion developed as a result of radiation therapy and surgery to the neck area in a patient with recurrent metastatic squamous cell carcinoma of the floor of the mouth. Laboratory findings of low thyroxine level and the findings of persistent hyponatremia and hypoosmolality of serum in spite of persistent sodium loss in the urine were helpful in diagnosing the problem. Treatment included thyroid hormone replacement and fluid restriction resulting in complete reversal of her condition. We believe that patients with head and neck cancer who have undergone a course of radiation to the neck, and particularly when thyroid function might have been altered by previous subtotal thyroidectomy as part of a curative resection, should be carefully followed with periodic thyroid function assays and serum electrolytes with particular attention to serum sodium values.


Plasma vitrification and re-use of non-combustible fiber reinforced plastic, gill net and waste glass.
Fiber reinforced plastic (FRP) composite material has widespread use in general tank, special chemical tank and body of yacht, etc. The purpose of this study is directed towards the volume reduction of non-combustible FRP by thermal plasma and recycling of vitrified slag with specific procedures. In this study, we have employed three main wastes such as, FRP, gill net and waste glass. The thermal molten process was applied to treat vitrified slag at high temperatures whereas in the post-heat treatment vitrified slags were mixed with specific additive and ground into powder form and then heat treated at high temperatures. With a two-stage heat treatment, the treated sample was generated into four crystalline phases, cristobalite, albite, anorthite and wollastonite. Fine and relatively high dense structures with desirable properties were obtained for samples treated by the two-stage heating treatment. Good physical and mechanical properties were achieved after heat treatment, and this study reveals that our results could be comparable with the commercial products.


Maternal regulation of the hypothalamic-pituitary-adrenal axis in the infant rat: the roles of feeding and stroking.
Twenty-four hours of maternal separation results in increased secretion of ACTH and corticosterone (CORT), suggesting the hypothalamic-pituitary-adrenal (HPA) axis is regulated by some aspect of maternal behavior. Previous results indicate that feeding plays a role in maintaining low levels of CORT in 12-day-old pups. In Experiment 1 basal and stress levels of CORT and ACTH were measured in maternally-deprived pups either provided or not with milk to determine whether: (1) feeding maintains ACTH secretion at low levels, and/or (2) feeding maintains the adrenal insensitive to ACTH. The results showed that, although ACTH levels were markedly low (compared to previous values reported by this laboratory) for both groups, only non-fed pups showed a robust increase in basal and stress CORT levels. During the deprivation period in Experiment 1, all pups were manually stroked to induce urination and defecation, suggesting an effect of stroking on ACTH secretion. Experiment 2 examined this hypothesis. Stroking suppressed stress-induced elevations of ACTH secretion due to maternal deprivation. CORT levels, however, were elevated in all deprived pups. The results indicate that maternal regulation of the infant's HPA axis occurs at multiple levels. Feeding appears to regulate adrenal sensitivity, whereas anogenital stroking inhibits the activation of centrally-controlled components of the axis.


Epidemic keratoconjunctivitis in India: electronic medical records-driven big data analytics report IV.
To describe the clinical profile of epidemic keratoconjunctivitis (EKC) in patients presenting to a multitier ophthalmology hospital network in India. This retrospective hospital-based study included 2 408 819 patients presenting between August 2010 and February 2020. Patients with a clinical diagnosis of EKC in at least one eye with a recent onset (≤1 week) were included as cases. The data were collected using the eyeSmart electronic medical record system. Overall, 21 196 (0.9%) new patients were diagnosed with EKC, of which 19 203 (90.6%) patients reported a recent onset (≤1 week) and were included for analysis. The median age was 32 (IQR: 22-45) years and adults (84.5%) were commonly affected. Most of the patients were male (62.1%) and unilateral (53.4%) affliction was commoner. The most common presenting symptom was redness (63.7%), followed by watering (42.1%). Preauricular lymphadenopathy or tenderness was documented in 1406 (7.3%) cases at presentation. A minority of the eyes had visual impairment worse than 20/200 (7.8%) due to associated ocular comorbidities. The involvement of the cornea was seen in 7338 (38.2%) patients and corneal signs included subepithelial infiltrates (26.3%), epithelial defect (1.4%), corneal oedema (0.9%) and filaments (0.4%). Of the patients who had corneal involvement, 496 (2.6%) patients had a chronic course beyond 1 month of which 105 (0.5%) had a course beyond 1 year. EKC is a self-limiting condition that is commonly unilateral and predominantly affects males. About one-third of the patients have corneal involvement which rarely has a chronic course.


Dietary Supplement and Prescription Medication Use Among US Military Service Members With Clinically Diagnosed Medical Conditions: The US Military Dietary Supplement Use Study.
Use of prescription medications (PMs) with dietary supplements (DSs) can be hazardous because of potential adverse interactions, but patterns of dual use in military service members (SMs) has not been examined. Investigate dual use of filled PMs (FPMs) and DSs, factors associated with dual use, and dual use among SMs with clinically diagnosed medical conditions (CDMCs). Cross-sectional. Data on FPMs and CDMCs were obtained from medical surveillance records. Between December 2018 and August 2019, participants completed a questionnaire on DS use in the previous 6 months. A stratified random sample of 26,880 SMs from all military services. Prevalence of dual use of FPMs with DSs within a 6-month period, demographic/lifestyle factors associated with dual use, and prevalence of dual use among SMs with CDMCs. Prevalences were calculated as percents, χ2 statistics examined differences across various strata of demographic and lifestyle characteristics, and univariable and multivariable logistic regression determined the odds of using FPMs with DSs for various CDMCs. About one-half (49%) of SMs had dual use of FPMs with DSs in the 6-month period. Dual use was higher among women; increased with older age, more formal education, higher body mass index, and more physical activity; was highest among American Indian SMs and lowest among Asian SMs; was higher among former tobacco users; and was highest among Army personnel and lowest among Marine Corps personnel. The overall prevalence of dual use in the 6-month period was higher among those with a CDMC than those without (62% vs 19%), and this relationship was maintained for 20 International Classification of Diseases, Revision 10, code groupings covering virtually all CDMCs. This is the first study to document a high prevalence of dual FPMs and DSs in SMs, especially among those with CDMCs.


Thiol-promoted catalytic synthesis of diphenolic acid with sulfonated hyperbranched poly(arylene oxindole)s.
Acid-catalyzed condensation of levulinic acid and phenol into high yields of diphenolic acid (>50%) is possible with a combination of sulfonated hyperbranched polymers and thiol promotors, either added as a physical mixture or bound to the polymer by ion-pairing.


Medical student stress: an elective course as a possibility of help.
The frequently observed stress of medical students worldwide leads them to have psychic suffering often leading to illness. Minor psychic disorders such as anxiety, depression and burnout, have a higher prevalence in these students than in the rest of random population. Different initiatives were tried to minimize the deleterious effects of the medical course and this article aims at showing the repercussions of a elective course that and was proposed as a possibility to help the students. A qualitative case study took place in a public Brazilian university as an elective discipline offered to medical students in 2013, offering coping strategies for professional stress. The data was collected through a semi-structured individual questionnaire that was anonymous, and given to students on the last day of the course, with 18 Likert scale questions about personal and behavioural changes observed after taking the course. Objective questions were asked about their perception of stress at the beginning and at the end of the course: the use of the coping strategies taught and the perception of the utility of the content. In addition, one open-ended question was asked about the meaning of the discipline to the students. The quantitative data was analysed with descriptive simple statistics and the qualitative with the support of the WebQDA software. The research project was approved by the ethics committee of the institution. The results showed that the course contributed positively to the students' academic life: 67% reported less symptoms of stress at the end of the course; 76% adopted new coping strategies; and 90% considered that this learning activity was useful for identifying stressors and sharing them with colleagues. The elective course produced benefits to the students, representing theoretical-practical learning and an opportunity for reflection and self-knowledge, which caused psychological, behavioural and lifestyle changes. It is recommended that further studies on this theme should be conducted.


Platelet-rich plasma releasate promotes angiogenesis in vitro and in vivo.
Platelet-rich plasma (PRP) is a plasma fraction in which several growth factors are concentrated at high levels. In recent years, the biological effects on various cells of the active soluble releasate that is isolated following platelet activation of PRP [PRP-releasate (PRPr)] have been reported. The purpose of this study was to determine the angiogenic effects of human PRPr in vitro and in vivo. PRPr was prepared from human whole blood using the double spin method and was activated with CaCl2 and autologous thrombin. PRPr stimulated proliferation, migration and tube formation of human umbilical vein endothelial cells (HUVECs) and in vivo angiogenesis-inducing ability in nude mice. PRPr led to the phosphorylation of Erk1/2 and Akt in HUVECs, and the induction of proliferation and migration by PRPr was suppressed by PRPr inhibitors PD98059 and LY294002. PRPr induces angiogenesis in vitro and in vivo, and the present findings suggest that the mechanism for this is activation of the ERK and phosphatidylinositol-3-kinase-Akt pathways. Our results demonstrate that PRPr is a promising autologous source for therapeutic angiogenesis in treating cardiovascular disease.


Estrogenic and progestational activity of 7alpha-methyl-19-nortestosterone, a synthetic androgen.
Synthetic androgens exhibit estrogenic/antiestrogenic and progestational activities in addition to their androgenic effects. To investigate the pharmacological action of the synthetic androgen, 7alpha-methyl-19-nortestosterone (MENT), we examined its action in female rodents. The criteria employed for estrogenic/antiestrogenic effects were, uterine weight increase, vaginal cornification, induction of progesterone receptors (PR) synthesis and stimulation of peroxidase activity in the uteri of ovariectomized rats and mice. MENT increased uterine weight in a dose dependent manner, but did not cause vaginal cornification or stimulate PR synthesis in the uterus. The uterotropic activity of MENT was 200-fold lower than that of estradiol. Estrogen receptor (ER) bound [3H]-E2 was displaced by E2 and MENT with ED50 values of 70 pg and 250 ng, respectively, a 3,500 fold difference in their binding affinity. The low binding of MENT to ER, in contrast to its relatively high uterotropic action, suggested that receptors other than ER may be involved in its action on the uterus. The progestational activity of MENT in immature rabbits using the McPhail index assay was comparable to that of progesterone. Binding affinities of MENT and progesterone to PR were also comparable. However, the action of MENT on the uterus does not seem to be a progestational effect since mifepristone, an antiprogestin, had no effect on MENT-induced uterine growth. Specific androgen receptors (AR) in uterine cytosol were demonstrated. The involvement of AR in MENT action was confirmed by using an antiandrogen (flutamide) and an antiestrogen (ICI-182) in ovariectomized mice. Although MENT did not block the uterotropic effect of E2, it inhibited the E2-induced cornification of vaginal epithelium, induction of uterine PR synthesis and increase in uterine peroxidase activity in ovariectomized rats. The antiestrogenic effect of MENT was also blocked by flutamide. These results suggest that the uterotropic and antiestrogenic effects of androgens are mediated via AR. It is concluded that the increase in uterine weight caused by MENT is attributable to its anabolic effects.


Clinical outcomes of different regimens of intravitreal Conbercept for the treatment of choroidal neovascularization secondary to pathological myopia.
To assess the clinical outcomes of two intravitreal injection regimens of Conbercept used to treat choroidal neovascularization secondary to pathological myopia (PM-CNV). A total of 72 eyes of 72 patients were treated: 39 eyes received a single injection followed by treatment pro re nata (1 + PRN); 33 eyes first received 3 consecutive monthly injections (3 + PRN) then followed by PRN. After initial injection, patients were followed up for 12 months. The mean age of 72 patients was 45.3 ± 5.1 years, with the mean diopter of -10.62 ± 3.24D. The best corrected visual acuity (BCVA) was 0.86 ± 0.23 LogMAR with 1 + PRN and 0.90 ± 0.19 LogMAR with 3 + PRN at baseline (P = 0.422), 0.36 ± 0.07 and 0.33 ± 0.05 LogMAR at month 3 (P = 0.026); and 0.33 ± 0.03 and 0.32 ± 0.02 LogMAR at month 12 (P = 0.096). The central retinal thickness (CRT) was 333.5 ± 22.7 μm with 1 + PRN and 341.2 ± 20.9 μm with 3 + PRN at baseline (P = 0.139), 281.53 ± 10.28 and 273.15 ± 13.24 μm at month 3 (P = 0.004); 266.83 ± 8.14 and 264.91 ± 9.27 μm at month 12 (P = 0.350). The number of injections in the 1 + PRN group was significantly lower than that observed in the 3 + PRN group (2.15 ± 1.06 versus 3.36 ± 0.74; P < 0.001). During the follow-up, no serious ocular complications and adverse reactions related to Conbercept and injections occurred. Both injection regimens resulted in similar visual outcomes in PM-CNV patients. The 1 + PRN regimen had fewer injections and might be more suitable in this patient population.


Short-term glucagon stimulation test of C-peptide effect on glucose utilization in patients with type 1 diabetes mellitus.
This work aimed to evaluate the use of a four-point glucagon stimulation test of C-peptide effect on glucose utilization in type 1 diabetic patients using a new mathematical model. A group of 32 type 1 diabetic patients and a group of 10 healthy control subjects underwent a four-point glucagon stimulation test with blood sampling at 0, 6, 15 and 30 min after 1 mg glucagon bolus intravenous administration. Pharmacokinetic and pharmacokinetic/pharmacodynamic models of C-peptide effect on glucose utilization versus area under curve (AUC) were used. A two-sample t test and ANOVA with Bonferroni correction were used to test the significance of differences between parameters. A significant difference between control and patient groups regarding the coefficient of whole-body glucose utilization and AUC C-peptide/AUC glucose ratio (p ≪ 0.001 and p = 0.002, respectively) was observed. The high correlation (r = 0.97) between modeled coefficient of whole-body glucose utilization and numerically calculated AUC C-peptide/AUC glucose ratio related to entire cohort indicated the stability of used method. The short-term four-point glucagon stimulation test allows the numerically calculated AUC C-peptide/AUC glucose ratio and/or the coefficient of whole-body glucose utilization calculated from model to be used to diagnostically identify type 1 diabetic patients.


Men and women show similar survival rates after breast cancer.
To compare the disease-free survival (DFS) and overall survival (OS) rates of men and women undergoing treatment for breast cancer. A retrospective cohort study of patients with breast cancer diagnosed and treated at the Cancer Hospital III of the National Cancer Institute of Brazil, Rio de Janeiro, Brazil, between 1999 and 2013. Male breast cancer cases were matched for age, year of diagnosis, and clinical staging to three female cases (1:3). Patient characteristics were abstracted from hospital records and medical charts. Cases were analyzed using descriptive statistics, and comparisons between the genders were performed using Kaplan-Meier curves and Cox regression analysis with 95% confidence intervals. The study population comprised 98 men and 294 women. There were significant differences (p < 0.05) between the genders for marital status, alcohol consumption, smoking, presence of hypertension and other comorbidities, histological type of tumor, expression of estrogen receptors, progesterone receptors, human epidermal growth factor receptor-type 2, type of breast surgery, neoadjuvant chemotherapy, adjuvant radiotherapy, and use of palliative bisphosphonate therapy. Five- and 10-year DFS rates were, respectively, 80.0 and 51.4% for men and 71.4 and 63.5% for women (p = 0.245), and 5- and 10-year OS rates were, respectively, 65.0 and 47.5% for men and 56.5 and 41.4% for women (p = 0.221). There was no significant difference in prognosis (DFS and OS rates) between the genders, but significant differences in sociodemographic and clinical characteristics were detected between male and female breast cancer cases.


[On an improved device for measuring skin tearing strength. Technical description and experimental results obtained from rat skin following therapy with topical corticoids (author's transl)].
Technical details of an improved method for measuring tensile behaviour of normal and treated rat skin are described. The apparatus has been developed specifically for skin specimens so that the extending force and the adequate strain rate until rupture are designed especially for this purpose. Skin is to be mounted in the jaws of the instrument in horizontal position. Preliminary biological data have been worked out.


Discrimination strategies in animal psychophysics and their role in understanding sensory receptor function.
Discrimination is defined in a restricted sense here as a precise and specifiable relation between stimuli and responses. Experimenter control of stimulation is one significant feature of this relation. It is suggested that there may be some important differences between discrimination of drugs and exteroceptive stimulation. However, a discussion of current strategies in animal psychophysics might uncover similarities between these two discrimination formats useful in formulating questions and designing future research. Traditionally animal psychophysics has focused on basic questions of acuity and sensitivity (threshold). Beyond their obvious value in the study of comparative sensory function and evolutionary development, these experiments have provided particularly important new insights into the understanding of peripheral sensory transduction and processing and their relation to perception. Our experiments have been carried out in animals whose hearing has been impaired by drugs and cryolesions, and relations have been sought between the subsequent hearing loss and the histopathological changes occurring in the auditory receptor cells of the inner ear. But threshold sensitivity is only one of many perceptual dimensions and tells us nothing of the discriminations that are made among stimuli which are clearly above minimum detectable levels. For example, discriminations occur along stimulus dimensions such as wavelength of light, sound pressure, acoustic frequency, and so on. Sensory systems also permit the accurate location of the source of stimulation at a distance, the selection of certain frequencies or wavelengths and the rejection of others, and finally the discrimination among very complex but biologically useful signals such as speech. Prototypical experiments are described; the results suggest significant and orderly relations with peripheral sensory processing mechanisms. The power of operant behavior to examine perception from a variety of perspectives is discussed.


Conformational epitope mapping of Pru du 6, a major allergen from almond nut.
Tree nuts are a widely consumed food. Although enjoyed safely by most individuals, allergic reactions to tree nuts, including almond, are not uncommon. Almond prunin (Pru du 6), an 11S globulin (legumin), is an abundant nut seed protein and a major allergen. Conformational epitope mapping studies of prunin have been performed with a murine monoclonal antibody (mAb) 4C10. This mAb reacts with non-reduced but not reduced prunin in immunoblotting assays, indicating the recognition of a conformational epitope. 4C10 competes with patient IgE, as assessed by ELISA, indicating clinical significance of the epitope. To characterize the 4C10 epitope, hydrogen/deuterium exchange (HDX) monitored by 14.5 T Fourier transform ion cyclotron resonance mass spectrometry (MS) was performed on the native prunin-4C10 complex and on uncomplexed native prunin. Several epitope candidate peptides that differ in deuterium uptake between the complexed and uncomplexed forms were identified. The epitope was further mapped by analyzing chimeric molecules incorporating segments of the homologous soybean allergen, Gly m 6, in immunoassays. These data indicate that the 4C10 epitope overlaps with a subset of patient IgE binding epitopes on almond prunin and further supports HDX-MS as a valid technique for mapping conformational epitopes.


Clinical roles of breast 3T MRI, FDG PET/CT, and breast ultrasound for asymptomatic women with an abnormal screening mammogram.
Magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) show promise for molecular cancer imaging. We evaluated 3T MRI, FDG PET/CT, and ultrasound images for asymptomatic women with an abnormal screening mammogram. The Institutional Review Board of Kaohsiung Veterans General Hospital (Kaohsiung, Taiwan) approved the study. Patients provided written informed consent. A total of 11,865 screening mammograms of 118,65 women were performed at our facility between January 2011 and December 2012. Fifty-three asymptomatic women (mean age, 53.3 years) whose screening mammograms had a Breast Imaging Reporting and Data System (BI-RADS) category of 4 or 5 were ultimately enrolled in this study. Breast 3T MRI, FDG PET/CT, and breast ultrasound were performed before biopsy. All imaging modalities were compared by lesion-by-lesion analyses. Fifty-nine breast lesions (28 malignant and 31 benign lesions) from 53 women were analyzed. The sensitivity, specificity, and accuracy for 28 breast cancers were 96%, 77%, and 86%, respectively, for breast 3T MRI; 50%, 100%, and 76%, respectively, for FDG PET,CT; and 61%, 87%, and 74%, respectively, for breast ultrasound. One 0.8-cm invasive breast cancer was missed by the screening mammogram, but detected by breast 3T MRI and FDG PET/CT. The sensitivity for detecting breast cancer was significantly higher with MRI than with PET/CT or ultrasound (for all, p < 0.01). The specificity for detecting breast cancer was significantly higher for PET/CT than for breast MRI (p = 0.02). The sensitivity exhibited by 3T breast MRI and FDG PET/CT for 16 noninvasive breast cancers was 94% and 25%, respectively. On screening mammograms, breast 3T MRI showed higher sensitivity but less specificity than FDG PET/CT for detecting asymptomatic breast cancers.


Association of serum levels of C-reactive protein with CRP-717 T/C polymorphism and viremia in HCV and HBV carriers.
The present study investigated the association of the rs2794521 polymorphism in the CRP gene in individuals with chronic hepatitis B and C, correlating it with markers of hepatic inflammation, fibrosis scores, viral load, and plasma protein levels. The study analyzed 185 blood samples obtained from patients with hepatitis B (n=74) and hepatitis C (n=111) and 300 samples from healthy donors. Genotyping was performed by real-time polymerase chain reaction, and protein levels were quantified using the automated immunoturbidimetric method. The TT genotype was the most frequent in all studied groups and was associated with higher plasma levels of the protein but not with the progression of liver disease. Low levels of C-reactive protein were associated with increased viremia and scores indicative of severe fibrosis and cirrhosis. The present results demonstrated a close relationship between the ability of the virus to replicate and cause liver damage and low serum concentrations of C-reactive protein. Future research may determine if these results can be interpreted as a possible form of escape for the virus by decreasing its action as an opsonin and decreasing phagocytosis, which are functions of C-reactive protein in the immune response.


Thaliporphine ameliorates cardiac depression in endotoxemic rats through attenuating TLR4 signaling in the downstream of TAK-1 phosphorylation and NF-κB signaling.
Thaliporphine was found to ameliorate endotoxin-induced circulatory failure and mortality in rodents. The aims of the present study were to assess whether thaliporphine could improve cardiac function in endotoxemic rats and to investigate the underlying mechanisms. Cardiac function was evaluated by pressure-volume loop analysis in pentobarbital-anesthetized rats 24 h after intravenous injection of lipopolysaccharide (LPS) (4 mg/kg) with or without thaliporphine (1 mg/kg, iv). The intracellular Ca(2+) transients, nitric oxide (NO), and reactive oxygen species (ROS) in enzymatically isolated ventricular cells were measured by fluorescent indicators. Western blotting was used to analyze the change of protein expression in response to LPS with or without thaliporphine in rat ventricle, H9C2 and Raw264.7 cells. Cardiac depression was found to coincide with the decreased intracellular Ca(2+) transients and the increased expression of nitrotyrosine on SERCA2 in rat ventricles after 24-h endotoxemia. Thaliporphine decreased intracellular NO and ROS level in ventricular cells and the nitrosylation of SERCA2, which resulted in recovering the functional properties of intracellular Ca(2+) handling and cardiac contraction. In H9C2 cells, LPS-induced nuclear translocation of nuclear factor kappa B (NF-κB) could be attenuated by thaliporphine. In Raw264.7 cells, thaliporphine attenuated LPS-induced TAK-1 phosphorylation and IκBα degradation in association with the inhibition of inducible nitric oxide synthase (iNOS) and tumor necrosis factor alpha (TNF-α) expression and the production of NO and ROS. In conclusion, thaliporphine ameliorates LPS-induced cardiac depression through attenuating TLR4 signaling in the downstream of TAK-1 phosphorylation and NF-κB signaling in both cardiomyocytes and macrophage to prevent cardiac SERCA2 from nitrosylation by peroxynitrite via decreasing iNOS and TNF-α expression.


A saturated fat/cholesterol avoidance scale: sex and ethnic differences in a biethnic population.
Avoidance of saturated fat and cholesterol by 1,210 Mexican Americans and 866 non-Hispanic whites was assessed as part of a population-based survey of diabetes and cardiovascular risk factors. Participants ranged in age from 25 to 64 years and resided in three socioeconomically distinct neighborhoods of San Antonio, TX: low income, middle income, and upper income. A scale was constructed to assess the degree to which individuals avoided six dietary sources of saturated fat and cholesterol. Women of both ethnic groups were found to avoid saturated fat and cholesterol to a greater degree than men, scoring higher on five of the six components of the scale. Saturated fat/cholesterol avoidance increased significantly with increased socioeconomic status in both ethnic groups. Although there were no ethnic differences in overall saturated fat/cholesterol avoidance, more non-Hispanic whites recognized milk, eggs, and visible fat on meat as food sources to avoid. The scale described in this paper provides useful information about the specific food components recognized as dietary sources of saturated fat and cholesterol and helps identify those population groups that would benefit from nutrition education programs. Because of its simplicity and ease of administration, the scale may be a useful tool in epidemiological research.


Relationship of corneal asphericity to intraocular lens power calculations after myopic laser in situ keratomileusis.
To examine whether corneal asphericity affects underestimation in the SRK/T intraocular lens (IOL) power calculation after myopic laser in situ keratomileusis (LASIK) and to evaluate the predictability of IOL power underestimation using the asphericity. Kitasato University, Kanagawa, and Miyata Eye Hospital, Miyazaki, Japan. Retrospective case series. The clinical records of eyes that had IOL implantation during cataract surgery after previous myopic LASIK between May 2008 and October 2014 were reviewed. For eyes with an available clinical history, the effect of manifest refraction spherical equivalent before LASIK, axial length, and the asphericity (Q value) on cataract surgery and the refractive error in the use of the SRK/T formula were examined using stepwise multiple regression analysis. Predictions with the resultant regression equation and significant factors were evaluated with Bland-Altman plots. Fifty-four eyes of 37 patients were included. The mean duration from LASIK to cataract surgery was 9.1 years ± 3.5 (SD) (range 2 to 14 years). Multiple regression analysis using 22 eyes of 22 patients resulted in a significant factor, which was the Q value (P < .001, R(2) = 0.80). The refractive errors in 53 eyes were predicted with tolerances of 64.5% and 87.0% within ±0.5 diopter (D) and within ±1.0 D, respectively. Bland-Altman analysis showed that 95% of the limitation range was 2.59 D. The corneal asphericity after myopic LASIK significantly correlated with the IOL power underestimation with use of the SRK/T formula. The refractive error could also be predicted well with the use of asphericity. None of the authors has a financial or proprietary interest in any material or method mentioned.


Progranulin inhibits fibrosis by interacting with and up-regulating DNAJC3 during mouse skin wound healing.
Scars place a heavy burden on both individuals and society. Our previous study found that reduction of progranulin (PGRN) promotes fibrogenesis in mouse skin wound healing. However, the underlying mechanisms have not been elucidated. Here, we report that PGRN overexpression decreases the expression of profibrotic genes alpha-smooth muscle actin (αSMA), serum response factor (SRF), and connective tissue growth factor (CTGF), thereby inhibiting skin fibrosis during wound repair. Bioinformatics analysis suggested that the heat shock protein (Hsp) 40 superfamily C3 (DNAJC3) is a potential downstream molecule of PGRN. Further experiments showed that PGRN interacts with and upregulates DNAJC3. Moreover, this antifibrotic effect was rescued by DNAJC3 knockdown. In summary, our study suggests that PGRN inhibits fibrosis by interacting with and upregulating DNAJC3 during wound healing in mouse skin. Our study provides a mechanistic explanation of the effect of PGRN on fibrogenesis in skin wound healing.


[The association of two single nucleotide polymorphisms in PRKCZ and UTS2 respectively with type 2 diabetes in Han people of northern China].
To probe the candidate susceptibility gene (s) of type 2 diabetes in the formal mapping region, 1p36.33-p36.23, in Han people of Northern China using single nucleotide polymorphisms (SNPs). 23 SNPs located in 10 candidate genes in the mapping region were chosen from public SNP domain by bioinformatic methods and single base extension (SBE) method were used to genotype the loci in 192 sporadic type 2 diabetes patients and 172 normal individuals to perform case-control study. Among the 23 SNPs, 8 were found to be common in Chinese population. There were statistically different in the allele frequency of 2 SNP, rs436045 in the protein kinase C/xi gene and rs228648 in Urotensin II gene between case and control groups. The two SNP may be associated with type 2 diabetes in Han people of China, which makes base for further study of the relation between the genes they located with type 2 diabetes.


Which exercise interventions are more helpful in treating primary obesity in young adults? A systematic review and Bayesian network meta-analysis.
Network meta-analysis was used to evaluate the effectiveness of different exercise interventions in the treatment of obesity in young people and recommend the most suitable exercise method. We searched five electronic databases for articles on obesity treatment in the youth population from inception to April 2022. The two researchers independently retrieved and screened the articles, carried out a quality assessment and data extraction, and carried out a network meta-analysis in the Bayesian framework in Stata software. A total of 32 original studies were included in the study, all randomized controlled trials (RCTs). High-intensity aerobic exercise may be the best way to reduce the weight of obese people; high-intensity aerobic training combined with resistance training may be the best way to reduce BMI and FAT%; moderate-intensity aerobic training combined with resistance training may be the best way to reduce the waistline; high-intensity aerobic exercise may be the best way to boost VO2max. Exercise interventions such as high-intensity aerobic training combined with resistance training can be considered and promoted as a non-drug treatment for primary obesity in young adults.


Suicide and Accidental Death Among Women With Primary Ovarian Cancer: A Population-Based Study.
Women with ovarian cancer had the highest suicidal rate among all patients with gynecological malignancies, but no large studies about suicide and accidental death for women with ovarian cancers in detail were conducted. We aimed to determine the relative risk of suicide and accidental death among patients with ovarian cancer to that of the general population, and to identify risk factors associated with suicide and accidental death. Data are from the SEER (surveillance, epidemiology, and end results) cancer registry of women diagnosed with ovarian cancer data from 18 registries for the years 1973-2016. The study population comprised 149,204 patients after inclusion and exclusion criteria were applied. Standardized mortality ratios (SMRs) were calculated and Fine-Gray models were fitted to identify risk factors associated with suicidal and accidental death among cancer patients, with stratifications on demographic and tumor-related characteristics. Women with ovarian cancer had a higher risk of suicide and accidental death than the cancer-free group [SMR = 1.86; 95% CI (1.54-2.25) and SMR = 1.54; 95% CI (1.39-1.71)]. Subgroup analysis indicated that only patients with type II epithelial ovarian cancer [SMR = 2.31; 95% CI (1.83-2.91)] had an increased risk of suicide, and those with type I and type II epithelial ovarian cancer [SMR = 1.65; 95% CI (1.39-1.97) and SMR = 1.49; 95% CI (1.30-1.70)] were at a higher risk of accidental death. Patients with ovarian cancer who were younger, white, diagnosed with high-grade, non-metastatic cancer and pelvic exenteration were at a higher risk of suicide. The advanced age, earlier year of diagnosis, and non-metastatic cancer were associated with a higher risk of accidental death. Additionally, pelvic exenteration increased the risk of suicide but not the risk of accidental death among women with primary ovarian cancer. Women with ovarian cancer had a higher risk of suicide and accidental death compared with the general population. The findings suggested that clinicians should identify high-risk subgroups of ovarian cancer patients for suicide and accidental death as early as possible, with appropriate prevention strategies.


Midline medulloblastoma versus astrocytoma: the position of the superior medullary velum as a sign for diagnosis.
We wish to describe the position of the superior medullary velum (SMV) in midline posterior fossa tumours as a sign in helping to distinguish between midline medulloblastoma and midline astrocytoma. Sagittal T1-weighted MRI images of 21 consecutive patients with histologically documented posterior fossa midline astrocytomas (nine cases) and medulloblastomas (12 cases) were reviewed, with respect to the position of the velum medullare superius. In all medulloblastomas the SMV was superiorly dislocated; in eight astrocytomas it was anteriorly and/or inferiorly disclocated; only in one astrocytoma the SMV presented upward dislocation. In the differential diagnosis between medulloblastoma and astrocytoma the upward dislocation of the SMV is strongly suggestive of medulloblastoma.


Determination of lung capillary blood volume and membrane diffusing capacity in man by the measurements of NO and CO transfer.
NO and CO lung transfer values (TL) were measured separately in 14 healthy subjects (7 men, 7 women), using the single breath technique. Five repetitive maneuvers were performed by each subject for TLNO and TLCO determinations. The inspired mixture contained either 8 ppm NO or 0.25% CO, with 2% He, 21% O2 in N2. In order to measure an appreciable fraction of NO in the alveolar gas it was necessary to shorten the breath holding time to 3 sec. TLNO was about five times greater than TLCO. This result suggests that the specific conductance of blood (theta) for NO is very high and that the second term of the second member of the equation 1/TLNO = 1/DmNO + 1/(theta NO.Qc) is therefore negligible. DmCO and Qc values can thus be computed from TLNO and TLCO measurements. The results obtained with this method are very close to those reported in the literature; for men DmCO = 79.0 +/- 14.3 ml.min-1.Torr-1, Qc = 78.0 +/- 13.2 ml and for women DmCO = 59.0 +/- 10.1 ml.min-1.Torr-1, Qc = 59.5 +/- 11.6 ml.


The Prognostic Significance of c-KIT Mutations in Core Binding Factor Acute Myeloid Leukemia.
Many recurrent mutations are encountered in core binding factor acute myeloid leukemia (CBF-AML) which may affect the prognosis. Approximately 20 to 45% of CBF-AML patients have KIT mutations which are having poor prognosis and high incidence of relapse. There is still insufficient data to categorize the patients with c-kit mutation into which risk group and there is a debate around whether Tyrosine kinase inhibitors can decrease the relapse risk and improve the prognosis of those patients. This study was conducted throughout a period of 3 years, where 102 CBF-AML were enrolled in our study. We analyzed the incidence of c-KIT exon 8 and 17 D816V mutations in CBF-AML patients and studied the prognosis. The prevalence of CBF-AML was 102 of 989 (10.3%), 13.7% and 8.7% in pediatrics and adults' groups respectively. c-KIT fragment mutation analysis revealed a mutant form in 27 of 102 (26.5%) patients. Exon 8 mutation was found in 4 of 40 pediatric and 2 of 62 adult patients, while exon 17 mutation was found in 9 of 40 pediatric and 12 of 62 adult patients. The c-KIT mutations was more common in t(8;21). There was no significant relationship between c-kit mutation and CR rates, while there was a significant inferior overall, disease free as well as progression free survival in the c-KIT mutant patients as compared to the wild group (P value .045, .036 and .024 respectively) in the pediatric group, however, this significance was not evident in the adults' group. According to our study, the results may suggest c-KIT mutation as a poor risk factor in pediatric CBF-AML.


Necrolytic migratory erythema, presenting as candidiasis, due to a pancreatic glucagonoma.
A 54-year-old male with diabetes, weight loss, glossitis and Candidiasis presented with the typical cutaneous eruption of necrolytic migratory erythema. The suspicion of pancreatic glucagonoma was confirmed by an elevated plasma glucagon level. Surgical removal of the pancreatic alpha cell tumor resulted in a complete disappearance of all symptoms. The importance of the recognition of the skin eruption of necrolytic migratory erythema as a clue to the presence of pancreatic glucagonoma is emphasized.


Hyperoside reduces albuminuria in diabetic nephropathy at the early stage through ameliorating renal damage and podocyte injury.
Diabetic nephropathy (DN) is one of the major microvascular complications in diabetes. Podocyte injury such as slit diaphragm effacement is regarded as a determinant in the occurrence and development of albuminuria in DN. In this study, we examined the effect of hyperoside, an active flavonoid glycoside, on proteinuria and renal damage in a streptozotocin-induced DN mouse model at the early stage. The results showed that oral administration of hyperoside (30 mg/kg/day for 4 weeks could significantly decrease urinary microalbumin excretion and glomerular hyperfiltration in DN mice, but did not affect the glucose and lipid metabolism. Periodic acid-Schiff staining and transmission electron microscopy showed that glomerular mesangial matrix expansion and podocyte process effacement in DN mice were significantly improved by hyperoside. Further investigations via immunofluorescence staining, real-time reverse transcription polymerase chain reaction and Western blot analysis showed that the decreased slit diaphragm protein nephrin and podocin mRNA expression and protein levels in DN mice were restored by hyperoside treatment. Collectively, these findings demonstrated that hyperoside could decrease albuminuria at the early stage of DN by ameliorating renal damage and podocyte injury.


Angiofibrolipoma of the larynx: Case report and literature review.
Angiofibrolipomas are one of the rarest variants of lipomas. Laryngeal origin of lipomatous tumors is also very rare. The nature and severity of symptoms depend on the location and the size of the laryngeal tumors. However, pedunculated of a 28-cm long tumor with the point of origin on the left arytenoepiglottic fold reached down to the esophagus and. in spite of slight dysphagia. remained asymptomatic for many years. In this case, a narrowing of the digestive tract was masked by an adaptation to the presence of a slowly growing mass. After surgical removal of the tumor and 18-month follow-up, the patient remains asymptomatic. Nonetheless, taking into consideration a possibility of recurrence or malignance, a postoperative regular 5-year follow-up was recommended. This case report illustrates the successful transoral resection of a polypoid-shaped angiofibrolipoma of the larynx. An easy and safe endoscopic procedure seemed to be successful in the case described.


Surgical side infections of the tracheostomy - A retrospective cohort study of patients with head and neck cancer in intensive care.
This study was conducted to reveal the relevant risk factors for surgical site infections (SSI) of the tracheostomy in ICU tracheostomy patients with oncologic history. Retrospectively, medical and ICU records of patients who received open tracheostomy in a uniform manner were investigated. Of 187 consecutive patients in total, patients with a peri/post-operative antibiotic prophylaxis (POABP) experienced significantly more Organ-Space SSI, whereas patients with a POABP developed less Superficial Incisional SSI and Deep Incisional SSI. Neck Dissection (p = 0.025), especially the more levels are included, and POABP (p = 0.005) have a significant impact on the occurrence of an SSI of the tracheostomy. Deep incisional SSI significantly prolonged a patient's dependency on a ventilator (p = 0.045, M = 3.92, SD = 4.718). The difference between Superficial Incisional, Deep Incisional and Organ-Space SSI should be taken in consideration regarding risk evaluation and treatment. Furthermore, a gram-negative facultative anaerobic biofilm should be taken into consideration in treatment options and thus an escalation regarding antibiotic treatment as a POABP. For fulminant SSI of the tracheostomy the use of piperacillin/tazobactam or 3rd generation cephalosporines or carbapenems is recommendable.


A novel and simple method for quantification of small, dense LDL.
A preponderance of small, dense (sd) LDL is strongly associated with the development of coronary heart disease, but the method for the measurement of sd LDL is too laborious for clinical use. We report a simple method for the quantification of sd LDL that is applicable to an autoanalyzer. This method consists of two steps: first, to precipitate the lipoprotein of density (d) <1.044 g/ml using heparin-magnesium; and second, to measure LDL-cholesterol in the supernatant by the homogeneous method or apolipoprotein B (apoB) by an immunoturbidometric assay. The cholesterol and apoB values obtained by the precipitation method (45 +/- 26 and 33 +/- 20 mg/dl, respectively) were similar to those obtained in the lipoprotein (d = 1.044-1.063) separated by ultracentrifugation (42 +/- 22 and 31 +/- 17 mg/dl, respectively), and there was an excellent correlation between the two methods for sd LDL-cholesterol (y = 1.05X + 1, r = 0.88, n = 69) and apoB (y = 1.07X, r = 0.90). Sd LDL values had a significant inverse correlation with LDL size. A high correlation was found between sd LDL-cholesterol and apoB values (r = 0.94). Sd LDL value was related to triglyceride, apoB, and LDL-cholesterol, but not to the buoyant LDL level. These results suggest that this precipitation method is a simple and rapid method for the measurement of sd LDL concentration.


The type of mutations induced by carbon-ion-beam irradiation of the filamentous fungus Neurospora crassa.
Heavy-ion beams are known to cause great damage to cellular components and are particularly renowned for their ability to generate DNA double-strand breaks (DSBs). To gain insight into the mutagenic effect of carbon-ion beams and how such damage is repaired by the cell, Neurospora crassa mutants deficient in one of three components involved in the repair of DSBs, nonhomologous end-joining (NHEJ), homologous recombination repair (HR), and the Mre11-Rad50-Xrs2 (MRX) complex, were irradiated with a carbon-ion beam and killing effect, mutation frequencies, and the type of mutation incurred by survivors were analysed. The sensitivity of the NHEJ-deficient strain (mus-52) was higher than that of the wild-type and the HR-deficient (mei-3) strains at low doses of radiation, but was little changed as the level increased. As a result both the wild-type and HR-deficient strains were more sensitive than the NHEJ-deficient strain at high radiation levels. In addition, the frequency of forward mutation at the adenine-3 (ad-3) loci of the NHEJ-deficient mutant was lower than that of the wild-type strain at all levels, while the mutation frequency of the HR-deficient strain was consistently ∼3-fold higher than the wild-type. From the comparison of mutation type of each strain, deletions were frequently observed in wild-type strain, whilst base substitution and deletion in the mus-52 and mei-3 strains. These mutations resulting from carbon-ion-beam irradiation depend on the mechanism invoked to cope with DSBs. Furthermore, in wild-type cells, these mechanisms likely compete to repair DSBs.


Advances in Intracranial Hemorrhage: Subarachnoid Hemorrhage and Intracerebral Hemorrhage.
Aneurysmal subarachnoid hemorrhage and intracerebral hemorrhage are devastating injuries causing significant morbidity and mortality. However, advancements made over decades have improved outcomes. This review summarizes a systematic approach to stabilize and treat these patient populations.


From shotgun to targeted proteomics: rapid Scout-MRM assay development for monitoring potential immunomarkers in Dreissena polymorpha.
A highly multiplexed liquid chromatography mass spectrometry-multiple reaction monitoring (MRM)-based assay has been developed for evaluating 107 candidate immune biomarkers in both hemocytes and plasma of the zebra mussel Dreissena polymorpha. The Scout-MRM strategy was employed for the first time, shortening the implementation of a targeted MRM bottom-up proteomics assay using selected immune protein-related peptides identified by shotgun discovery proteogenomics. This strategy relies on spiking scout peptides during the discovery phase and using them to build and deploy the MRM targeted proteomics method. It proved to be highly relevant, since about 90% of the targeted peptides and proteins were monitored and rapidly measured in both hemocyte and plasma samples. The sample preparation protocol was optimized by evaluating the digestion efficiency of tryptic peptides over time. The accuracy and precision of 50 stable isotope-labeled peptides were evaluated for use as internal standards. Finally, the specificity of the transitions was thoroughly assessed to ensure the reliable measurement of protein biomarkers. Several analytical and biological validation criteria were evaluated across hemocytes and plasma samples exposed ex vivo to biological contaminants, resulting in the validation of two Scout-MRM assays for the relative quantitation of 85 and 89 proteins in hemocytes and plasma, respectively. Graphical abstract.


Effects of different curing methods on edible quality and myofibrillar protein characteristics of pork.
This study aimed to investigate the effects of standing curing (SC), tumbling curing (TC), vacuum tumbling curing (VTC) and ultrasonic-assisted curing (UAC) on the edible quality of black pork and property of myofibrillar proteins (MPs) extracted from black pork. The results showed that all curing methods could improve the marinating absorptivity and the gel water retention of black pork, the solubility and surface hydrophobicity of myofibrillar proteins, and reduce the cooking loss and shear force of black pork, the hydrogen bond content of myofibrillar proteins and the gel whiteness compared with the control group (SC). The result of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that the concentration of protein bands by VTC treatment was decreased obviously. In addition, the result of the scanning electron microscope (SEM) presented that tumbling and ultrasound treatment would destroy the structure of muscle fibers and make them loose and disordered.


Drug targeting--current aspects and future prospects.
A variety of materials have been suggested as carriers for the delivery of drugs to specific sites of action. Drugs may be covalently bound to carriers or physically trapped within particulate carriers. Likely mechanisms of action of targeting agents are described. The results of in vitro and in vivo experiments are reviewed and the prospective clinical uses of each type of carrier are discussed. In particular, monoclonal antibodies are promising agents for the targeting of cytotoxic agents to malignant cells. Radiolabelled monoclonal antibodies are likely to develop as agents for the radio-imaging of tumours which will prove useful in the diagnosis and treatment of cancer.


Hyperthermia by bathing in a hot spring improves cardiovascular functions and reduces the production of inflammatory cytokines in patients with chronic heart failure.
Balneotherapy has been shown to reduce systemic blood pressure in healthy volunteers. Hyperthermia might ameliorate the inflammatory status in heart failure through improving cardiac function. The purpose of this study was to examine the beneficial effects of balneotherapy in patients with chronic heart failure (CHF). Thirty-two patients with systolic CHF classified as New York Heart Association functional status II or III were randomized to divide either a balneotherapy group or a control group. The patients in the balneotherapy group were immersed in a hot spring at 40°C for 10 min daily for 2 weeks; the control group patients took a shower daily. The left ventricular ejection fraction (EF) and cardiothoracic ratio (CTR) were evaluated and plasma brain natriuretic peptide (BNP), high-sensitivity C-reactive protein (hsCRP), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 levels were measured. The clinical symptoms improved after 2 weeks of hot spring therapy. Although the heart rate did not change, clinical symptoms, CTR, EF, and BNP were significantly improved. Moreover, the inflammatory responses, including hsCRP, TNF-α and IL-6 decreased significantly after balneotherapy. The improvement of BNP correlates with the changes in inflammatory biomarkers. Repeated hyperthermia by bathing in a hot spring is therefore considered to improve the cardiac and inflammatory status in patients with CHF.


Effect of low alcohol dose on behavioral "despair" in rats neonatally treated with antidepressant drugs.
Rat pups were treated with monoamine uptake inhibiting antidepressant drugs, desipramine, imipramine or nomifensine (5 mg/kg) during the second and third postnatal weeks, and their later behavioral "despair," measured by Porsolt's swim test, was examined. At the age of two months, the desipramine-treated rats showed lengthened immobility in the swim test, and thus probably increased behavioral "despair." They also responded to 1 g/kg alcohol by shortening the immobility to the level of control rats. Neonatal treatment with either imipramine or nomifensine did not affect the swim test behavior. The results suggest that a low, stimulatory dose of alcohol was able to reverse the lengthened immobility in the swim test of rats treated with desipramine during the early postnatal period.


Natural compounds in the regulation of proteostatic pathways: An invincible artillery against stress, ageing, and diseases.
Cells have different sets of molecules for performing an array of physiological functions. Nucleic acids have stored and carried the information throughout evolution, whereas proteins have been attributed to performing most of the cellular functions. To perform these functions, proteins need to have a unique conformation and a definite lifespan. These attributes are achieved by a highly coordinated protein quality control (PQC) system comprising chaperones to fold the proteins in a proper three-dimensional structure, ubiquitin-proteasome system for selective degradation of proteins, and autophagy for bulk clearance of cell debris. Many kinds of stresses and perturbations may lead to the weakening of these protective cellular machinery, leading to the unfolding and aggregation of cellular proteins and the occurrence of numerous pathological conditions. However, modulating the expression and functional efficiency of molecular chaperones, E3 ubiquitin ligases, and autophagic proteins may diminish cellular proteotoxic load and mitigate various pathological effects. Natural medicine and small molecule-based therapies have been well-documented for their effectiveness in modulating these pathways and reestablishing the lost proteostasis inside the cells to combat disease conditions. The present article summarizes various similar reports and highlights the importance of the molecules obtained from natural sources in disease therapeutics.


Complete single-stage management of left colon cancer obstruction with a new device.
A newly developed device that enables easy intraoperative colonic irrigation and subsequent colonoscopy was introduced recently. To evaluate the efficacy of the single-stage procedure with a new device and the significance of on-table colonoscopy, 112 patients with obstructive left colon cancer were recruited. Primary anastomosis after tumor resection was performed in 104 cases. The volume of saline used for irrigation averaged 13.5 l over 12.1 min. Subsequent colonoscopic examination added an average of 10.4 min to the operative time. There were three anastomotic leaks, two wound infections, four acute renal failures, and two operative mortalities. On-table colonoscopy resulted in extended resection in 17 cases. The new device enabled safe, simple, and time-saving, single-stage surgical management of left colon cancer obstruction. The ability to perform on-table colonoscopy enabled treatment and recognition of synchronous bowel pathology.


Levator trauma after vaginal delivery.
To date, the evidence on pelvic floor injury in labor remains sketchy due to a lack of prospective studies comparing pelvic floor imaging before and after childbirth. We intended to define the incidence of major trauma to the pubovisceral muscle. A total of 61 nulliparous women were seen at 36-40 weeks of gestation in a prospective observational study. The assessment included an interview and 3-dimensional translabial ultrasound and was repeated 2-6 months postpartum. Fifty women (82%) were seen postpartum. Of the 39 women delivered vaginally, levator avulsion was diagnosed in 14 (36%, 95% confidence interval 21-51%). Among those delivered vaginally, there were associations with higher maternal age (P = .10), vaginal operative delivery (P = .07), and worsened stress incontinence postpartum (P = .02). Avulsion of the inferomedial aspects of the levator ani from the pelvic sidewall occurred in approximately one third of all women delivered vaginally and was associated with stress incontinence 3 months after childbirth.


Admission to a psychiatric unit and changes in tobacco smoking.
Smoking and withdrawal from smoking complicates the assessment and treatment of mental illness. We aimed to establish whether psychiatric inpatients smoke different amounts after admission than beforehand and, if so, to find out why. Forty-three inpatients on a working age adult psychiatry ward completed self-report questionnaires about smoking habits. Those who smoked a different amount after admission had a follow-up interview to find out why they thought this had occurred. The interview incorporated qualitative and quantitative aspects which were analysed accordingly.Fifty-six percent of participants were smokers before admission, rising to 70% afterwards. Of the smokers, 17% smoked less after admission, and 63% smoked more. The average number of cigarettes smoked per person per day increased from five to thirteen. The main reasons for smoking more were boredom, stress and the wish to socialise.


Prostatic abscess owing to anaerobic bacteria.
Abscess of the prostate is seen infrequently. We report a prostatic abscess owing to anaerobic bacteria in a 46-year-old man with a 10-year history of irritable voiding symptoms. Preoperative computerized tomography confirmed the diagnosis of prostatic abscess, which was treated with transurethral resection and broad-spectrum antibiotics.


Beta adrenergic modulation of cardiac rhythm in a rat model of altered sympathetic neural development.
We previously have shown that treatment of neonatal rats (days 1-10) with Nerve Growth Factor (NGF) or its antibody (Ab) modifies alpha-adrenergic receptor-effector coupling, such that innervated hearts at day 10 show high levels of a 41 kDa GTP regulatory protein (G protein) that is a substrate for pertussis toxin and that links the alpha 1-receptor to the Na/K pump. This receptor-effector pathway results in alpha adrenergic-induced decreases in automaticity. In contrast, non-innervated hearts at day 10 show lower levels of the pertussis toxin sensitive G-protein and increases in automaticity induced by alpha-agonist. We now report the effects of administration of NGF, Ab or placebo on beta-adrenergic receptor-effector coupling in neonatal rats. Rats were administered NGF, Ab or placebo on days 1-10 of life. On day 10, the beta-receptor number and affinity and the stimulatory G-protein, Gs, were equivalent across groups. Moreover, the ventricular automatic response to beta-adrenergic receptor stimulation was equivalent across groups suggesting there was no change in receptor-effector coupling as a result of the difference in innervation. These results on beta-adrenergic receptor-effector coupling considered in light of our prior studies on alpha-adrenergic coupling suggest that the development of sympathetic innervation is more a determinant of alpha than beta adrenergic modulation of ventricular rhythm.


Hospitalizations for critically ill children with traumatic brain injuries: a longitudinal analysis.
This study examines the incidence, utilization of procedures, and outcomes for critically ill children hospitalized with traumatic brain injury over the period 1988-1999 to describe the benefits of improved treatment. Retrospective analysis of hospital discharges was conducted using data from the Health Care Cost and Utilization Project Nationwide Inpatient Sample that approximates a 20% sample of U.S. acute care hospitals. Hospital inpatient stays from all types of U.S. community hospitals. The study sample included all children aged 0-21 with a primary or secondary ICD-9-CM diagnosis code for traumatic brain injury and a procedure code for either endotracheal intubation or mechanical ventilation. None. Deaths occurring during hospitalization were used to calculate mortality rates. Use of intracranial pressure monitoring and surgical openings of the skull were investigated as markers for the aggressiveness of treatment. Patients were further classified by insurance status, household income, and hospital characteristics. Over the 12-yr study period, mortality rates decreased 8 percentage points whereas utilization of intracranial pressure monitoring increased by 11 percentage points. The trend toward more aggressive management of traumatic brain injury corresponded with improved hospital outcomes over time. Lack of insurance was associated with vastly worse outcomes. An estimated 6,437 children survived their traumatic brain injury hospitalization because of improved treatment, and 1,418 children died because of increased mortality risk associated with being uninsured. Improved treatment was valued at approximately dollar 17 billion, whereas acute care hospitalization costs increased by dollar 1.5 billion (in constant 2000 dollars). Increased mortality in uninsured children was associated with a dollar 3.76 billion loss in economic benefits. More aggressive management of pediatric traumatic brain injury appears to have contributed to reduced mortality rates over time and saved thousands of lives. Additional lives could be saved if mortality rates could be equalized between insured and uninsured children.


Surface-enhanced Raman scattering in local optical fields of silver and gold nanoaggregates-from single-molecule Raman spectroscopy to ultrasensitive probing in live cells.
This Account discusses surface-enhanced Raman scattering at extremely high enhancement levels that can occur for molecules attached to silver and gold nanoclusters. Strongly enhanced and highly confined local optical fields enable surface-enhanced Stokes and anti-Stokes Raman spectroscopy of single molecules even under nonresonant excitation conditions as well as extremely large effective cross sections in two-photon excited Raman spectroscopy. The ability for very sensitive and spatially confined molecular structural probing makes gold and silver nanoclusters very promising tools for studies of small structures in biological materials, such as cellular compartments.


Allergological Importance of Invertebrate Glutathione Transferases in Tropical Environments.
Glutathione-S transferases (GSTs) are part of a ubiquitous family of dimeric proteins that participate in detoxification reactions. It has been demonstrated that various GSTs induce allergic reactions in humans: those originating from house dust mites (HDM), cockroaches, and helminths being the best characterized. Evaluation of their allergenic activity suggests that they have a clinical impact. GST allergens belong to different classes: mu (Blo t 8, Der p 8, Der f 8, and Tyr p 8), sigma (Bla g 5 and Asc s 13), or delta (Per a 5). Also, IgE-binding molecules belonging to the pi-class have been discovered in helminths, but they are not officially recognized as allergens. In this review, we describe some aspects of the biology of GST, analyze their allergenic activity, and explore the structural aspects and clinical impact of their cross-reactivity.


Selection of molecular chirality by extremely weak chiral interactions under far-from-equilibrium conditions.
A general formalism for chiral symmetry breaking in far-from-equilibrium chemical systems is presented. It is pointed out that slow passage through the transition point makes the system sensitive to very weak, but systematic, chiral influences. The general implications of this process for the origin of biomolecular chirality is discussed.


Reduction of Cerebral Edema via an Osmotic Transport Device Improves Functional Outcome after Traumatic Brain Injury in Mice.
Traumatic brain injury (TBI), the foremost cause of morbidity and mortality in persons under 45 years of age worldwide, leads to about 200,000 victims requiring hospitalization and approximately 52,000 deaths per year in the United States. TBI is characterized by cerebral edema leading to raised intracranial pressure, brain herniation, and subsequent death. Current therapies for TBI treatment are often ineffective, thus novel therapies are needed. Recent studies have shown that an osmotic transport device (OTD) is capable of reducing brain water content and improving survival in mice with severe cerebral edema. Here we compare the effects of a craniectomy and an OTD plus craniectomy on neurological function in mice after TBI. Animals treated with a craniectomy plus an OTD had significantly better neurological function 2 days after TBI compared with those treated with craniectomy only. This study suggests that an OTD for severe brain swelling may improve patient functional outcome. Future studies include a more comprehensive neurological examination, including long-term memory tests.