Pore size-mediated macrophage M1 to M2 transition affects osseointegration of 3D-printed PEEK scaffolds.
Increasing evidence indicates that macrophages play an important role in angiogenesis and bone regeneration. Because the phenotypic polarization of macrophage is extremely sensitive to the pore size of materials, poly(ether-ether-ketone) (PEEK) scaffolds with pore sizes of 0, 200, and 400 μm were prepared, and the influence of pore size-mediated macrophage polarization on subsequent angiogenesis and osteogenesis was examined. The interaction results of macrophages and scaffolds indicated that macrophages were responsive to the pore size of three-dimensional (3D)-printed PEEK scaffolds, and large pore size scaffolds showed greater potential in inducing M1 to M2 transition of macrophage and enhanced macrophage secretion of high concentrations of osteogenesis-related and angiogenesis-related cytokines. When human umbilical vein endothelial cells (HUVECs) and bone marrow mesenchymal stem cells (BMSCs) were cultured in the conditioned medium derived from co-culture of macrophages and scaffolds, HUVECs showed good angiogenic responses in terms of cell migration and angiogenic gene expression, while BMSCs showed good osteogenic differentiation effect in in vitro mineralization and osteogenesis-related gene expression. The results of bone defect repair showed that the bone volume/total volume ratio and trabecular thickness of the large pore size PEEK scaffold were significantly higher, and it had better biomechanical properties and achieved a better osseointegration effect. Our data demonstrate that large-pore PEEK scaffolds promote angiogenesis and osteogenic differentiation in vitro and osseointegration in vivo, most likely because scaffolds with larger pore size are able to mediate a higher degree of M1 to M2 transition in macrophages.


Antiviral sensitivities of the acute retinal necrosis syndrome virus.
Varicella zoster was isolated from the vitreous of a patient with the acute retinal necrosis (ARN) syndrome. We utilized a plaque reduction assay to determine the in vitro susceptibility of the ARN isolate to 6 antiviral drugs. The effective doses for 50% inhibition of plaque numbers were 5.3 microM for for acyclovir, 4.7 microM for DHPG, 8.7 microM for ARA-A, 100.7 microM for phosphonoacetic acid, 0.07 microM for BVdU and 2.4 microM for IUdR. Similar inhibitory values were obtained for the OKA vaccine strain of varicella zoster virus. These data do not support the notion that the ARN strain may represent a mutant of varicella zoster virus with significant alterations in either the viral thymidase kinase or DNA polymerase genes based upon its antiviral sensitivities. The implications of these results regarding the role of antiviral chemotherapy in the ARN syndrome are discussed.


Seven-signal proteomic signature for detection of operable pancreatic ductal adenocarcinoma and their discrimination from autoimmune pancreatitis.
There is urgent need for biomarkers that provide early detection of pancreatic ductal adenocarcinoma (PDAC) as well as discrimination of autoimmune pancreatitis, as current clinical approaches are not suitably accurate for precise diagnosis. We used mass spectrometry to analyze protein profiles of more than 300 plasma specimens obtained from PDAC, noncancerous pancreatic diseases including autoimmune pancreatitis patients and healthy subjects. We obtained 1063 proteomic signals from 160 plasma samples in the training cohort. A proteomic signature consisting of 7 mass spectrometry signals was used for construction of a proteomic model for detection of PDAC patients. Using the test cohort, we confirmed that this proteomic model had discrimination power equal to that observed with the training cohort. The overall sensitivity and specificity for detection of cancer patients were 82.6% and 90.9%, respectively. Notably, 62.5% of the stage I and II cases were detected by our proteomic model. We also found that 100% of autoimmune pancreatitis patients were correctly assigned as noncancerous individuals. In the present paper, we developed a proteomic model that was shown able to detect early-stage PDAC patients. In addition, our model appeared capable of discriminating patients with autoimmune pancreatitis from those with PDAC.


Resistance of hypervirulent Klebsiella pneumoniae to cathepsin B-mediated pyroptosis in murine macrophages.
Hypervirulent Klebsiella pneumoniae (hvKp) has emerged as a clinically significant global pathogen in the last decade. However, the host immune responses of the macrophages during hvKp infection are largely unknown. In the present study, we aimed to compare the cytotoxic effects of hvKp and classical K. pneumoniae (cKp) in murine macrophages. We found that the activation of caspase-1 -dependent pyroptosis was higher in cKp-infected macrophages compared with that in hvKp-infected macrophages. In Caspase-1 deficiency macrophages, pyroptosis diminished during infection. Both hvKp and cKp strains led to nucleotide-binding and oligomerization domain-like receptor protein 3 (NLRP3) inflammasome formation and lysosomal cathepsin B activation, thus resulting in pyroptosis. Compared with the cKp strain, the hvKp strain inhibited these phenomena in murine macrophages. HvKp infection resulted in different levels of pyroptosis via the activation of cathepsin B-NLRP3-caspase-1 in murine macrophages. Therefore, the manipulation of pyroptotic cell death is a potential target for host response during hvKp infection in macrophages.


Effects of Chromium on Glucose Tolerance in Infants Receiving Parenteral Nutrition Therapy.
Early hyperglycemia is prevalent in preterm infants receiving parenteral nutrition (PN) therapy. Chromium improves glucose tolerance by potentiating the action of insulin. Therefore, we hypothesized that supplementing PN with chromium would improve glucose tolerance and PN calorie delivery in infants during the first week of life. We collected data on neonates receiving PN initiated at birth with chromium (0.2 mcg/kg/d) started either on days 5-7 (group A) vs day 1 (group B) on PN and compared glucose tolerance and PN calorie administration over the first week of life. For similar mean serum glucose concentrations between group A (n = 348) and B (n = 358) (107 ± 48 vs 111 ± 52 mg/dL, P = .3), infants in group B tolerated higher glucose infusion rates and received more PN calories during the first week of life: 8.4 ± 2 vs 8 ± 2 mg/kg/min (P < .001) and 74.8 ± 23 vs 71.5 ± 12 kcal/kg/d (P = .017), respectively. The difference in calories delivered was more pronounced among very low birth weight (VLBW) infants compared with infants >1500 g: 76.5 ± 14 vs 72.4 ± 11 kcal/kg/d (P = .009) and 73.8 ± 27 vs 70.3 ± 12 kcal/kg/d (P = .079), respectively. PN chromium supplementation resulted in better glucose tolerance and calorie delivery during the first week of life, especially in VLBW infants. This supports chromium's essential role in enhancing glucose tolerance during PN therapy in VLBW infants at risk for early hyperglycemia.


[Paper disk granuloma method for experimental granuloma in rats (author's transl)].
The paper disk granuloma (PDG) method is a newly devised procedure for the screening of antiinflammatory drugs and was compared with the cotton pellet (CP) method. Results obtained were as follows; in the CP method, formation of granuloma was observed on the 1st day after the implantation of CP. On the 3rd day, maximum weight, protein and nucleic acids in granuloma were observed. The granuloma produced by PDG method was too small to collect on the 1st day. Weight and protein content of granuloma reached the peak on the 2nd or 3rd day. With respect to nucleic acids, maximum amounts were found on the 6th day. The incorporation of 3H-uridine into RNA was increased in the early stage of the formation of granuloma in both methods. The maximum incorporation of 3H-thymidine into DNA was noted on the 2nd day in CP method, and on the 3rd day in PDG method. Development of granuloma in the PDG method was different from that in CP method with respect to the synthesis of DNA. Antigranuloma action of fluocinolone acetonide (FA) was more marked in the PDG method than in the CP method, suggesting that the PDG method is more sensitive for screening of antiinflammatory drugs. Granuloma produced by the PDG method was also prevented and therapeutically suppressed by certain non-steroidal antiinflammatory drugs. ED50 values of applied FA, phenylbutazone, and 3-o-phthaloxy glycyrrhetinate were 27 microgram/kg, 91 mg/kg, and 66 mg/kg, respectively.


Time course of VMN lesion effects on lordosis and proceptive behavior in female hamsters.
Previous studies suggest that ultrasound production by female hamsters is better able than other reproductive behaviors to recover from an initial drop caused by damage to the ventromedial hypothalamus (VMN). At the same time, few studies have examined the time course of such lesion effects. To remedy this, female hamsters were observed before and after control operations or VMN lesions. The behaviors considered were ultrasound production, lordosis, approach, and vaginal marking. Ultrasound production, lordosis, and approach were affected by lesions, permitting the description of the time course of each of these effects. Only ultrasound rates showed evidence of recovery, which culminated in rates significantly above those observed preoperatively in the same animals. This suggests that ultrasound production is unusual in its response to VMN damage and that the underlying mechanism could be of interest in studies of the processes that determine recovery from brain damage.


Mutans streptococci oral colonization in 12-30-month-old Brazilian children over a one-year follow-up period.
The infection levels of mutans streptococci were investigated during a one-year follow-up in children aged 12 to 30 months attending school nurseries where a sucrose-rich diet was provided. Oral levels of mutans streptococci obtained from 101 children at baseline and after a one-year follow-up were compared by age, number of teeth, feeding habits, and presence of visible plaque at baseline. Baseline predictors and changes in mutans streptococci levels during the study were compared to caries incidence after one year. Fluctuations in mutans streptococci levels during the follow-up period were not related to feeding habits or presence of visible plaque. Mutans streptococci levels increased after one year among children aged 12 to 24 months, while a significantly higher proportion of those aged 25-30 months showed a decrease in mutans streptococci levels during the study. Multiple logistic regression analysis suggested that high levels of mutans streptococci (> or = 100 cfu) at baseline were associated with a higher caries increment, while reduction in mutans streptococci was negatively associated with caries incidence. Our data suggest that despite early mutans streptococci infection and high exposure to sucrose, mutans streptococci may achieve relatively stable levels after 2 years of age. Heavy colonization by mutans streptococci in an early age was related to an extremely high caries incidence during childhood, while decreasing levels of mutans streptococci can be associated to the decrease in caries activity.


Evaluating newer generation intraocular lens calculation formulas in manual versus femtosecond laser-assisted cataract surgery.
To determine the refractive accuracy of the Haigis, Barrett Universal II (Barrett), and Hill-radial basis function 2.0 (Hill-RBF) intraocular lens (IOL) power calculations formulas in eyes undergoing manual cataract surgery (MCS) and refractive femtosecond laser-assisted cataract surgery (ReLACS). This was a REB-approved, retrospective interventional comparative case series of 158 eyes of 158 patients who had preoperative biometry completed using the IOL Master 700 and underwent implantation of a Tecnis IOL following uncomplicated cataract surgery using either MCS or ReLACS. Target spherical equivalence (SE) was predicted using the Haigis, Barrett, and Hill-RBF formulas. An older generation formula (Hoffer Q) was included in the analysis. Mean refractive error (ME) was calculated one month postoperatively. The lens factors of all formulas were retrospectively optimized to set the ME to 0 for each formula across all eyes. The median absolute errors (MedAE) and the proportion of eyes achieving an absolute error (AE) within 0.5 diopters (D) were compared between the two formulas among MCS and ReLACS eyes, respectively. Of the 158 eyes studied, 64 eyes underwent MCS and 94 eyes underwent ReLACS. Among MCS eyes, the MedAE did not differ between the formulas (P=0.59), however among ReLACS eyes, Barrett and Hill-RBF were more accurate (P=0.001). Barrett and Hill-RBF were both more likely to yield AE<0.5 D among both groups (P<0.001). The Barrett and Hill-RBF formula lead to greater refractive accuracy and likelihood of refractive success when compare to Haigis in eyes undergoing ReLACS.


Immunohistochemical detection of Ca antigen in normal, dysplastic and neoplastic squamous epithelia of the human uterine cervix.
Immunohistochemical staining was performed on biopsies and cytological samples from normal, dysplastic and neoplastic squamous epithelia using the monoclonal Ca 1 antibody. The results of staining 92 biopsies and 20 cytological samples are described and it is reported that positive staining with Ca 1 antibody was detected in normal, dysplastic and neoplastic epithelia. The role of the Ca 1 antibody in the study of cervical cancer is discussed.


[Association hyperlipidemia and retinal hard exudates in diabetic retinopathy].
Diabetes mellitus is usually accompagned with dyslipidemia, which can be correlated with diabetic retinopathy (DR). The aim of the study is to determine the relation between DR and hyperlipidemia. We studied prospectively 64 diabetic patients classified into 2 groups: the first associated diabetics having dyslipidemia (n=34) and the second without dyslipidemia (n=30). The mean follow up was 11 months. We observed a high frequency of retinal hard exudates in diabetics with dyslipidemia in comparison with the second group (32% versus 10%). The control of dyslipidemia is recommended in diabetic patients.


[The hypotensive effect of aromatic amidines and imidazolines].
Some amidine, diamidine and diimidazoline derivatives were tested on their ability to lower the blood pressure of the rat. Except for 5-amidino-2-phenylindole (271/179) all substances led to a short-lasting hypotension, the dose relationship of some of which was investigated. The biscationic character was a prerequisite for a strong hypotensive action. The predominantly peripheral origin of the blood pressure lowering action was shown for the substances pentamidine, diminazene, 6-amidino-2- (4-amidinophenyl)-indole (102/198), 5-amidino-2-(4-amidinophenyl) - benzofurane (150/49) and 2,6-diamidinoindole (261/115). A parasympathomimetic and histaminic efficiency could be excluded. The pressor effect of norepinephrine (noradrenaline) was reduced under the influence of pentamidine, diminacene and 102/198. With the dog 102/198 and 261/115 showed a diminution of heart rate and force as well as a vasodilatory effect. Using the rat, different cardiovascular parameters behaved analogous. Pentamidine, diminazene, 102/198 and 261/115 increased the force of contraction of the isolated rat atrium. Toxic effects were observed in doses as high as 0,5 mmol/l and l mmol/l. Pentamidine reduced the heart rate of the isolated atrium in a dose-dependent manner. Taking into account the in vitro results, the heart effects were interpreted as being reflectory. In the isolated rat aorta preparation the aforementioned substances in low doses shifted the dose-response curves of norepinephrine to the right, whereas higher doses also reduced the maximum contraction. Considering the results on the intact animal, a direct action of the diamidines on vascular smooth muscle was discussed.


Administration of medicines. Midwifery basics.
Midwifery Basics is a series of articles that cover the main clinical skills underpinning midwifery practice. The series uses National Occupational Standards (Care Sector Consortium 1998) as a framework to identify the areas of competence that students need to achieve in order to master clinical skills. This format is combined with the use of 'triggers' to prompt the student to identify what she needs to know in order to care for a client in such a situation. The information that follows then enables the student to fill in the gaps in her knowledge.


The relationship between the use of digital display devices and headphones and primary headaches in children.
Headache represents the most common neurologic symptom in children. In this study, we investigated the relationship between watching television, listening to music with headphones, smartphone, tablet, and computer use, and primary headaches in children. We aimed to determine whether primary headache in children is associated with excessive use of digital display devices and headphones and whether reducing the use of digital display devices and headphones affects primary headache. The study included 69 children with primary headaches and 64 with no headaches as a control group. All subjects were evaluated for demographic and headache characteristics and the use of digital display devices and headphones. Our recommendation for patients and families was to decrease the use of digital display devices and headphones, and the headache burden was re-evaluated after one month. Headache frequency was more common in patients who watched television and used smartphones or tablets for more than 6 hours per day. Using a smartphone or tablet for more than 3 hours daily was more common in the study group than the control group. Headache frequency decreased in all patients one month after the digital imaging device and headphones were restricted. Watching television and using a smartphone or tablet strongly associates with primary headaches during childhood.


Experience using two CT-guided stereotactic biopsy methods.
15 patients had intracranial CT-guided stereotactic biopsies. Biopsies were performed either with a Riechert-Mundinger stereotactic frame modified for use in the CT or by using the CT scan to establish the relationship of the intracranial lesion to identifiable bony landmarks, and subsequently performing the biopsy in a standard stereotactic frame. Both systems provided safe and accurate methods for obtaining intracranial tissue.


Pressure ulcers and occipital alopecia in Operation Iraqi Freedom polytrauma casualties.
Several of the casualties from Operation Iraqi Freedom arriving at one Veterans Administration (VA) polytrauma rehabilitation center (PRC) were noted to have occipital pressure ulcers or hair loss. The objective of this study was to determine the prevalence and severity of pressure-related injuries in VA PRC admissions. A retrospective review of admissions from active duty from 2004 to 2006 was performed. Thirty-eight percent of admissions to this VA PRC had pressure-related injuries on the day of admission. Casualties from Iraq had a higher rate of pressure ulcers (53%) than did those from elsewhere (22%). Occipital lesions constituted 50% of non-stage I pressure ulcers and were more severe than those of the sacrum or extremities. Further epidemiological research should be performed to identify risk factors for pressure injury in the military continuum of care, by linking specific military medical evacuation and treatment processes and characteristics of casualties with outcomes.


Rhenium and technetium complexes that bind to amyloid-β plaques.
Alzheimer's disease is associated with the presence of insoluble protein deposits in the brain called amyloid plaques. The major constituent of these deposits is aggregated amyloid-β peptide. Technetium-99m complexes that bind to amyloid-β plaques could provide important diagnostic information on amyloid-β plaque burden using Single Photon Emission Computed Tomography (SPECT). Tridentate ligands with a stilbene functional group were used to form complexes with the fac-[M(I)(CO)3](+) (M = Re or (99m)Tc) core. The rhenium carbonyl complexes with tridentate co-ligands that included a stilbene functional group and a dimethylamino substituent bound to amyloid-β present in human frontal cortex brain tissue from subjects with Alzheimer's disease. This chemistry was extended to make the analogous [(99m)Tc(I)(CO)3](+) complexes and the complexes were sufficiently stable in human serum. Whilst the lipophilicity (log D7.4) of the technetium complexes appeared ideally suited for penetration of the blood-brain barrier, preliminary biodistribution studies in an AD mouse model (APP/PS1) revealed relatively low brain uptake (0.24% ID g(-1) at 2 min post injection).


Some new observations on the functional anatomy of the lower cervical spine.
The ligaments are a major stabilizing component of the cervical spine and are critical for spinal stability as well as stabilization therapy. Relatively little information is available on the anatomic details and function of the cervical ligaments. Fifteen fresh cervical spines were dissected and the ligaments examined grossly and functionally. Eight different intrinsic ligaments of the lower cervical spine were identified. The largest and most rigid of these are the annulus fibrosus, posterior longitudinal ligament, and capsular ligament. By virtue of their size and certain biomechanical observations, these ligaments stabilize the cervical spine. The other ligaments play a more specialized and secondary role. The intertransverse ligaments, although thin and frail, are consistently found and appear to limit rotation and lateral bending, the anterior longitudinal ligament limits extension and the interspinous and supraspinous ligaments limit spinal flexion. Under physiologic conditions, the elastic ligamentum flavum permits extension of the spine without impinging upon the spinal cord or nerve roots. As a group, the ligaments of the cervical spine control motion within finite limits without jeopardizing spinal cord or nerve root function.


Contemporary cystectomy with pelvic node dissection compared to preoperative radiation therapy plus cystectomy in management of invasive bladder cancer.
Between August 1971 and August 1982, 197 consecutive patients underwent single stage radical cystectomy with pelvic lymph node dissection and urinary diversion as definitive management of high grade, invasive bladder cancer. In 100 patients 1,600 rad of radiation therapy were given for 4 days preoperatively and 97 patients underwent an operation only. Although not constituting a prospective randomized study, an analysis of these 2 groups of patients managed during an 11-year period by the same surgical team, using identical surgical technique, provides useful information that questions the benefit of preoperative radiation therapy in the management of high grade, invasive bladder cancer. Other factors, such as improved surgical technique with meticulous pelvic node dissection as well as better preoperative and postoperative care, may be responsible for survival results of contemporary surgery only that equal those reported following combination therapy protocols using preoperative radiation therapy. Contemporary surgery with or without preoperative radiation therapy yielded a 5-year survival rate free of tumor of 75 per cent for patients with pathologic stages P2 and P3A disease, 44 per cent with P3A and P3B disease, and 36 per cent with P4 disease and positive pelvic nodes.


A high-throughput cell-based assay to identify specific inhibitors of transcription factor AP-1.
The oncogenic transcription factor AP-1 (activator protein-1) is required for tumor promotion and progression. Identification of novel and specific AP-1 inhibitors would be beneficial for cancer prevention and therapy. The authors have developed a high-throughput assay to screen synthetic and natural product libraries for noncytotoxic inhibitors of mitogen-activated AP-1 activity. The cell-based high-throughput screen is conducted in a 384-well format using a fluorescent resonance energy transfer (FRET) substrate to quantify the activity of a beta-lactamase reporter under the control of an AP-1-dependent promoter. The ratiometric FRET readout makes this assay extremely robust and reproducible, particularly for use with natural product extracts. To eliminate false positives due to cell killing, a cytotoxicity assay was incorporated. The AP-1 beta-lactamase reporter was validated with inhibitors of kinases located upstream of AP-1 and with known natural product inhibitors of AP-1 (nordihydroguaiaretic acid and curcumin). The assay was able to identify other known AP-1 inhibitors and protein kinase C modulators, as well as a number of chemically diverse compounds with unknown mechanisms of action from natural products libraries. Application to natural product extracts identified hits from a range of taxonomic groups. Screening of synthetic compounds and natural products should identify novel AP-1 inhibitors that may be useful in the prevention and treatment of cancers.


[Schwannomas. Clinical and pathological study of 85 cases].
A survey of the files of the Department of Neuropathology at the Mexican Neurological Institute, disclosed a total of 100 biopsies from 85 patients, 47 of whom females, with the histological diagnosis of Schwannoma. The survey comprised a period between July 1985 and June 1990. Schwannomas accounted for 4.08 per cent of 2,447 biopsies during that period. The age range was from 15 to 69 years with and average of 37.6 years. In 64 cases the tumors were localized intracranially, and in 18 within the spinal canal. The eighth never was the origin in 57 cases, the fifth in two, and the seventh in one; in four other cases the origin could not be ascertained. The intraspinal tumors were cervical in seven cases thoracic in nine, and lumbosacral in two. The most common clinical findings in 52 cases were decreased audition, increased intracranial pressure in 20, cerebellar involvement in 17, trigeminal in 16, facial paresis in 16, oculomotor disorder in six and motor neurone impairment in five.


Japanese encephalitis virus in India: An update on virus genotypes.
Japanese encephalitis (JE) is a leading cause of viral encephalitis in Southeast Asia. It is a serious public health issue in India, and cases have been emerging in newer areas of the country. Although vaccination efforts have already been initiated in the country since 2006 and later through the Universal Immunization Programme in 2011, still a significant reduction in the number of cases has to be achieved since an escalating trend of JE incidence has been reported in certain States such as Assam, Uttar Pradesh and West Bengal. Moreover, fresh cases of JE have been reported from certain pockets in Odisha as well. Despite the mass JE vaccination programme implemented in prioritized endemic zones in the country in 2011, a shift in the age group of JE virus (JEV) infection was noticed affecting the adult population in West Bengal. The recent detection of the circulation of genotype I (GI) in Gorakhpur, Uttar Pradesh and the co-circulation of GI and genotype III (GIII) in West Bengal are probably a warning signal for the public health personnel to strengthen the surveillance system in all endemic hotspots in the country. The abrupt emergence of JEV genotype V (GV) in China and Korea in 2009, after its first detection in Malaya in 1952, endemic countries have been cautioned to strengthen their surveillance, because GV has been suspected of getting dispersed efficiently in other parts of Asia. Moreover, the reduced protection efficiency of the JEV GIII-based vaccine against the JEV genotype V further warrants careful evaluation of the ongoing vaccination strategies in the endemic countries, anticipating the possible incursion of GV and its impact on future control strategies. In view of the above facts, the present communication reviews the current knowledge on the molecular epidemiology of JEV in India vis-a-vis the global scenario and discusses the future priorities in JEV research in India for effectively designing control strategies.


Carcinoid syndrome and disorders of systemic mast-cell activation including systemic mastocytosis.
Diagnostic approaches, clinical characteristics, and (briefly) therapy of the carcinoid syndrome and disorders of systemic mast cell activation are outlined. Mediators responsible for the humoral manifestations of the two syndromes are discussed. Because some of the clinical features of both disorders are similar (in particular, flushing), specific attention is given to the clinical differentiation of these disorders.


Isolation and characterization of two cDNA clones encoding ATP-sulfurylases from potato by complementation of a yeast mutant.
Sulfur plays an important role in plants, being used for the biosynthesis of amino acids, sulfolipids and secondary metabolites. After uptake sulfate is activated and subsequently reduced to sulfide or serves as donor for sulfurylation reactions. The first step in the activation of sulfate in all cases studied so far is catalyzed by the enzyme ATP-sulfurylase (E.C. 126.96.36.199.) which catalyzes the formation of adenosine-5'-phosphosulfate (APS). Two cDNA clones from potato encoding ATP-sulfurylases were identified following transformation of a Saccharomyces cerevisiae mutant deficient in ATP-sulfurylase activity with a cDNA library from potato source leaf poly(A)+ RNA cloned in a yeast expression vector. Several transformants were able to grow on a medium with sulfate as the only sulfur source, this ability being strictly linked to the presence of two classes of cDNAs. The clones StMet3-1 and StMet3-2 were further analyzed. DNA analysis revealed an open reading frame encoding a protein with a molecular mass of 48 kDa in the case of StMet3-1 and 52 kDa for StMet3-2. The deduced polypeptides are 88% identical at the amino acid level. The clone StMet3-2 has a 48 amino acid N-terminal extension which shows common features of a chloroplast transit peptide. Sequence comparison of the ATP-sulfurylase Met3 from Saccharomyces cerevisiae with the cDNA StMet3-1 (StMet3-2) reveals 31% (30%) identity at the amino acid level. Protein extracts from the yeast mutant transformed with the clone StMet3-1 displayed ATP-sulfurylase activity. RNA blot analysis demonstrated the expression of both genes in potato leaves, root and stem, but not in tubers.(ABSTRACT TRUNCATED AT 250 WORDS)


Dermal necrosis following coumarin: is it immunologically induced?
Two patients with dermal necrosis due to anticoagulation therapy with warfarin are reported. Both patients demonstrated some disturbance in immunological function. It appears possible that warfarin may act as a hapten in the induction of hypersensitivity to the drug. It is recommended that future cases should be studied to determine whether there is a defect in immunoregulation, and whether circulating immune complexes are responsible for the typical skin lesions.


Congenital adrenal hyperplasia in Blacks.
Two patients with salt-losing adrenal hyperplasia are reported. The occurrence of this condition among Blacks in Southern Africa has not yet been recorded. Both patients presented in the first month of life with dehydration, although they did not have diarrhoea. One was a boy, and the other a girl who had signs of virilisation. The typical biochemical changes of this condition were demonstrated. Congenital adrenal hyperplasia appears to be less common in Blacks than in Whites.


One-pot carbonization synthesis of europium-doped carbon quantum dots for highly selective detection of tetracycline.
The detection of tetracycline is of great significance because of its damaging effects on human health, such as renal toxicity and hemolytic anemia. Any release of tetracycline into the surrounding environment can produce bacterial drug resistance. We develop a new sensitive and selective detection approach for tetracycline in complex water samples by preparing europium-doped carbon quantum dots (Eu-CQDs) through a simple and rapid carbonization method operating at 200 °C for 5 min. The Eu-CQDs are characterized by blue photoluminescence, excitation-wavelength-dependent emission and excellent stability. Importantly, the fluorescence of the Eu-CQDs can be quenched efficiently by tetracycline, based on the strong inner filter effect mechanism between Eu-CQDs and tetracycline, making the fluorescence intensity ratio (I 0/I) of the Eu-CQDs at 465 nm correlate linearly with the concentration of tetracycline in the range of 0.5-200 μM, with a limit of detection of 0.3 μM. This shows the broad applicability of the Eu-CQDs in pursuing the concepts of simplicity and specificity for analytical purposes.


TXNDC5, a newly discovered disulfide isomerase with a key role in cell physiology and pathology.
Thioredoxin domain-containing 5 (TXNDC5) is a member of the protein disulfide isomerase family, acting as a chaperone of endoplasmic reticulum under not fully characterized conditions As a result, TXNDC5 interacts with many cell proteins, contributing to their proper folding and correct formation of disulfide bonds through its thioredoxin domains. Moreover, it can also work as an electron transfer reaction, recovering the functional isoform of other protein disulfide isomerases, replacing reduced glutathione in its role. Finally, it also acts as a cellular adapter, interacting with the N-terminal domain of adiponectin receptor. As can be inferred from all these functions, TXNDC5 plays an important role in cell physiology; therefore, dysregulation of its expression is associated with oxidative stress, cell ageing and a large range of pathologies such as arthritis, cancer, diabetes, neurodegenerative diseases, vitiligo and virus infections. Its implication in all these important diseases has made TXNDC5 a susceptible biomarker or even a potential pharmacological target.


Nemaline myopathy as a cause of sleep hypoventilation.
Two siblings, a 14.5-year-old boy and his 11.5-year-old sister, with congenital nemaline myopathy presented with severe respiratory failure and, in the case of the older patient, with cor pulmonale and systemic hypertension. The children were treated initially by continuous mechanical ventilation, but after a few weeks they only required ventilation at night. At the start of treatment, both were found to have a decreased ventilatory response to CO2 which apparently improved during 4 to 5 years of follow-up treatment. It has not been possible to wean them from nocturnal mechanical ventilation, but during the daytime they attend school and function almost normally. It is postulated that respiratory failure in nemaline myopathy may not be related to the severity of the muscle weakness but may result from a disturbance of the feedback required for normal control of breathing.


Effect of Nozzle Geometry on the Flow Dynamics and Resistance Inside and Outside the Cone-Straight Nozzle.
The cone-straight nozzle has been commonly utilized in various applications, such as cleaning, cutting, and drilling, and hence investigated extensively with simulations and experiments. However, the internal flow patterns and dynamics, as well as the influence of internal flow on jetting performance, remain unclear. In this study, we carry out both experiments and computational fluid dynamics to understand the effect of different converging angles of the cone-straight nozzle on internal and external flow patterns. Nozzle flows are simulated by a large eddy simulations model and further compared with the experimental flow fields obtained by a particle image velocimetry (PIV) method. Nozzles with different converging angles and throat lengths have been used experimentally. The influence of nozzle converging angle, throat length, and inlet flow speed on flow field, skin friction resistance, and viscous force is discussed. Associated boundary layer transition and separation are investigated comparatively. The flow discharge coefficient and flow core length are measured by the PIV test system with a high-pressure pump. The experimental results show that a specific converging angle and flow speed can cause the boundary layer transition and separation. Skin friction resistance increases first and then decreases with the increase of inlet flow speed when the angle is larger than 20°. The resistance decreases gradually when the angle is lower than 15°. Importantly, the skin friction resistance remains a lower level when the converging angle is 15°, in agreement with the previous research results. The experimental results show that the nozzle with a converging angle of 10° or 15° has a higher discharge coefficient and a better cluster capacity. The nozzle with a throat length of 3 times the outlet diameter has a longer flow core. Considering the nozzle size, the nozzle with a converging angle of 15° and a throat length of 3 times the diameter of the outlet is suggested when the nozzle is used in jetting for obtaining a longer jetting distance.


Increased Level of Long Non-Coding RNA MALAT1 is a Common Feature of Amoeboid Invasion.
The ability of cancer cells to adopt various migration modes (the plasticity of cancer cell invasiveness) is a substantive obstacle in the treatment of metastasis, yet still an incompletely understood process. We performed a comparison of publicly available transcriptomic datasets from various cell types undergoing a switch between the mesenchymal and amoeboid migration modes. Strikingly, lncRNA MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) was one of three genes that were found upregulated in all amoeboid cells analyzed. Accordingly, downregulation of MALAT1 in predominantly amoeboid cell lines A375m2 and A2058 resulted in decrease of active RhoA (Ras homolog family member A) and was accompanied by the amoeboid-mesenchymal transition in A375m2 cells. Moreover, MALAT1 downregulation in amoeboid cells led to increased cell proliferation. Our work is the first to address the role of MALAT1 in MAT/AMT (mesenchymal to amoeboid transition/amoeboid to mesenchymal transition) and suggests that increased MALAT1 expression is a common feature of amoeboid cells.


Cefoxitin-Serum Creatinine Interference in a Patient With Nontuberculous Mycobacteria Ventriculomeningitis.
Cefoxitin is a second-generation cephamycin antibiotic, which at concentrations ≥100 µg/mL is known to modestly interfere, for up to 2 hours post-infusion, with serum creatinine measurement via the traditional Jaffe-based assay. We report a case of a severe serum creatinine elevation while utilizing cefoxitin as a component of an antimicrobial regimen in a critically ill patient with Mycobacterium abscessus ventriculomeningitis. Our results, both via patient serum analysis and a cefoxitin spiking experiment, demonstrate interference despite the utilization of improved modern Jaffe-based assays. In fact, the cefoxitin-creatinine interference may be clinically relevant at concentrations 3 times lower than that listed in the package insert and may display more than a modest interference at typical therapeutic concentrations.


Molecular insights into the interaction of the ribosomal stalk protein with elongation factor 1α.
In all organisms, the large ribosomal subunit contains multiple copies of a flexible protein, the so-called 'stalk'. The C-terminal domain (CTD) of the stalk interacts directly with the translational GTPase factors, and this interaction is required for factor-dependent activity on the ribosome. Here we have determined the structure of a complex of the CTD of the archaeal stalk protein aP1 and the GDP-bound archaeal elongation factor aEF1α at 2.3 Å resolution. The structure showed that the CTD of aP1 formed a long extended α-helix, which bound to a cleft between domains 1 and 3 of aEF1α, and bridged these domains. This binding between the CTD of aP1 and the aEF1α•GDP complex was formed mainly by hydrophobic interactions. The docking analysis showed that the CTD of aP1 can bind to aEF1α•GDP located on the ribosome. An additional biochemical assay demonstrated that the CTD of aP1 also bound to the aEF1α•GTP•aminoacyl-tRNA complex. These results suggest that the CTD of aP1 interacts with aEF1α at various stages in translation. Furthermore, phylogenetic perspectives and functional analyses suggested that the eukaryotic stalk protein also interacts directly with domains 1 and 3 of eEF1α, in a manner similar to the interaction of archaeal aP1 with aEF1α.


Photophysical properties of ruthenium(II) polypyridyl-gold(I) ethynyl dyads and triads containing mono- or diethynylphenanthroline incorporated into gold(I) triphenylphosphine organometallics.
A new ruthenium(II)-gold(I) dyad, [Ru(bpy)(2){5-{(PPh(3))-Au-C[tripe bond]C}-phen}](PF(6))(2) (2), with a different substituted site compared to [Ru(bpy)(2){3-{(PPh(3))-Au-C[triple bond]C}-phen}](PF(6))(2) (1), and a triad, [Ru(bpy)(2){3,6-bis{(PPh(3))-Au-C[triple bond]C}-phen}](PF(6))(2) (3), with an unsymmetric diethynylphenanthroline relative to [Ru(bpy)(2){3,8-bis{(PPh(3))-Au-C[triple bond]C}-phen}](PF(6))(2) (4) have been prepared. These four ruthenium(II)-gold(I) compounds showed typical metal-to-ligand charge-transfer (MLCT) absorption bands in the 400-550 nm region and a lowest energy pi-pi* absorption involved with the gold(I) perturbation in the 300-400 nm region. Broad emission bands assignable to the triplet MLCT transition were definitely observed in all compounds, indicating that the hybrid architecture constructed with Ru(II)-polypyridyl and Au(I)-ethynyl units converts the blue-green gold(I) perturbed pi-pi* phosphorescence into an orange MLCT-based emission. The transient absorption difference spectra of four compounds showed the difference in the electron transfer process between 2 and other compounds 1, 3, and 4 under the excited state. Ru(II)-Au(I) compounds except for 2 receive the supposed charge injection from a ruthenium center to an extended pi-conjugated ethynyl-substituted phenanthroline, which contains one or two gold(I) organometallic unit(s), while 2 undergoes the electron transfer process from the ruthenium center not to the 5-ethynylphenanthroline but to one of the bipyridyl ligands under the excited state. This hypothesis is supported by the deflection of the spots of 2 and [Ru(bpy)(3)](PF(6))(2) from a linear correlation line in a plot of E(0-0) versus DeltaE(1/2), which was based on the electrochemical and emission data of Ru(II)-Au(I) compounds and mononuclear ruthenium(II) polypyridyl complexes.


The Application of a New Maximum Color Contrast Sensitivity Test to the Early Prediction of Chiasma Damage in Cases of Pituitary Adenoma: The Pilot Study.
Our objective was to estimate the maximum color contrast sensitivity (MCCS) thresholds in individuals with chiasma opticum damage. The pilot study tested 41 people with pituitary adenoma (PA) and 100 age- and gender-matched controls. Patients were divided into two groups according to PA size, PA ≤1 cm or PA >1 cm. A new MCCS test program was used for color discrimination. The mean total error score (TES) of MCCS was 1.8 in the PA ≤1 cm group (standard deviation [SD], 0.38), 3.5 in the PA >1 cm group (SD, 0.96), and 1.4 in the control group (SD, 0.31; p < 0.001). There was a positive correlation between tumor size and MCCS result (r = 0.648, p < 0.01). In the group that had PA-producing hormones, the TES was 2.5 (SD, 1.09), compared to 4.2 value in the non-functioning PA group of patients that did not have clinically significant hormone excess (SD, 3.16; p < 0.01). In patients with normal visual acuity (VA) or visual field MCCS, the TES was 3.3 (SD, 1.8), while that in patients with VA <0.00 was 4.6 (SD, 2.9). Results of the MCCS test TES were 1.9 times better in patients with PA ≤1 cm compared to patients with PA >1 cm (p < 0.01). In PA patients with normal VA, the TES was 2.35 times worse than that of healthy persons (p < 0.01).


Spectroscopic investigation on interaction of biogenic, Croton bonplandianum leaves extract mediated potential bactericidal silver nanoparticles with human hemoglobin and human serum albumin.
The green synthesis of nanoparticles has received increasing attention due to the growing demand to produce safe, cost-effective, and eco-friendly technology for nanomaterials synthesis. We report on the use of aqueous Croton bonplandianum (Family: Euphorbiaceae, Genus: Croton) leaves extract for the preparation of silver nanoparticles (AgNPs) without using any external reducing and stabilizing agent. Ultraviolet-visible spectroscopy showed maximum absorbance at 446 nm due to surface plasmon resonance of AgNPs. Energy dispersive X-ray spectra also supported the existence of AgNPs. An average diameter (d = ~17.4 nm) of the spherical AgNPs was determined from the transmission electron microscopic images. Hydrodynamic size (d = ~21.1 nm) was determined by dynamic light scattering. Fourier transform infrared analysis designed that the functional groups like O-H, N-H, [Formula: see text], CONH2, and COOH participated in the AgNPs formation. The negative zeta potential value (-19.3 mV) of the AgNPs indicated its dispersion and stability. The AgNPs exhibited strong antibacterial activity against Escherichia coli ATCC 25922 and 1.5 nM proved to be minimum inhibitory concentration for it. Hemolysis assay demonstrated the blood compatibility of the AgNPs toward human RBCs. The binding affinity of the AgNPs toward human hemoglobin and human serum albumin (HSA) was also determined by means of fluorescence spectroscopy. The circular dichroism spectroscopy revealed that the native structures of human hemoglobin and HSA remain unchanged, but its secondary structures were slightly changed upon interaction with AgNPs. Overall, it can be concluded that the AgNPs may be applied in the area of nanomedicines.


[Results of the Bankart-Müller operation for habitual luxation of the shoulder (author's transl)].
After presenting the topographical and pathological basis for the habitual luxation of the shoulder joint, our experience with the Bankart-Müller operation on 38 of our own patients was described. The results are characterized as very good, particularly two years and longer after the operation.


Cochlear implant candidacy and performance trends in children.
Data from Clarion cochlear implant pediatric clinical trials were examined retrospectively to uncover trends in candidacy and postimplant benefit over time. In particular, age at implantation, educational setting, and communication mode were examined with respect to speech perception performance after implantation. The results showed that 1) age at implantation is decreasing, 2) children in oral education programs obtain more benefit from a cochlear implant than children in total communication programs, 3) children who undergo implantation before 2 years of age show greater benefit than children who undergo implantation between 2 and 3 years of age, 4) more younger children are using oral communication than older children, and 5) more children with good auditory skills before implantation and more residual hearing are undergoing implantation. In sum, in the 11 years since implants have been available to children in the United States, candidacy criteria have evolved and benefit has increased as cochlear implant technology has advanced.


Exploring the potential for a mass media campaign to influence support for a ban on tobacco promotion at the point of sale.
This study explores whether exposure to advertisements that focus on the negative effects of tobacco industry advertising and promotion at the point of sale (anti-POS advertising) influence: (i) attitude toward POS advertising; (ii) perceived impact of POS advertising on youth smoking; and (iii) support for a ban on tobacco promotion at the POS among adult non-smokers in New York. Data are from a split-sample, experimental study, using an online media tracking survey with embedded TV, radio and print advertising. Exposure to anti-POS advertising was associated with higher odds of holding a negative attitude toward POS advertising (OR 2.43, P < 0.001) and support for a ban on tobacco promotion at the POS (OR 1.77, P < 0.05), but not with perceived impact of POS tobacco advertisements on youth smoking. Findings suggest the possibility that a mass media campaign could be used to influence public attitude toward POS advertising and support for a ban on tobacco promotion at the POS.


Estimation of covariate-dependent Markov transition probabilities from nested case-control data.
Multi-state models are used to describe situations where individuals may move among a finite number of states defined by specific conditions of health, including death. The transition intensities of the models are described by proportional hazards models, and it is reviewed how estimation of the regression parameters and the baseline transition intensities may be performed when only nested case-control data are available for all or some of the transitions. The regression parameter estimates and the estimates of baseline transition intensities are combined to give estimates of the integrated transition intensities for specified covariate histories, and from these estimates covariate-dependent Markov transition probabilities are derived.


HONO Production from Gypsum Surfaces Following Exposure to NO2 and HNO3: Roles of Relative Humidity and Light Source.
Nitrous acid (HONO) is a toxic household pollutant and a major source of indoor OH radicals. The high surface-to-volume ratio and diverse lighting conditions make the indoor photochemistry of HONO complex. This study demonstrates surface uptake of NO2 and gaseous HNO3 followed by gas-phase HONO generation on gypsum surfaces, model system for drywall, under reaction conditions appropriate for an indoor air environment. Tens of parts per billion of steady-state HONO are detected under these experimental conditions. Mechanistic insight into this heterogeneous photochemistry is obtained by exploring the roles of material compositions, relative humidities, and light sources. NO2 and HNO3 are adsorbed onto drywall surfaces, which can generate HONO under illumination and under dark conditions. Photoenhanced HONO generation is observed for illumination with a solar simulator as well as with the common indoor light sources such as compact fluorescence light and incandescent light bulbs. Incandescent light sources release more HONO and NO2 near the light source compared to the solar radiation. Overall, HONO production on the gypsum surface increases with the increase of RH up to 70% relative humidity; above that, the gaseous HONO level decreases due to surface loss. Heterogeneous hydrolysis of NO2 is predicted to be the dominant HONO generation channel, where NO2 is produced through the photolysis of surface-adsorbed nitrates. This hydrolysis reaction predominantly occurs in the first layer of surface-adsorbed water.


Multispectral quantitative magnetic resonance imaging of brain iron stores: a theoretical perspective.
To review published magnetic resonance imaging (MRI) iron quantification techniques in the context of quantitative MRI and MR relaxation theories. To analyze comparatively and as a function of age the simultaneous measurements of the proton density (PD), the relaxation times (T1 and T2), and the longitudinal to transverse relaxation times ratio (T1/T2) of brain regions known to accumulate iron preferentially. Twenty-seven human subjects were scanned with the mixed turbo spin echo pulse sequence, which is multispectral in PD, T1, and T2. Quantitative MRI (Q-MRI) maps of PD, T1, T2, and T1/T2 were generated, and region of interest measurements were performed in 5 brain regions, namely, frontal white matter (WM), genu of corpus callosum, caudate nucleus, putamen, and globus pallidus. Relaxation time measurements are consistent with results of others and provide further confirmation to our basic understanding of the relaxation effects of iron stores in the brain. Specifically, we found that the iron-rich globus pallidus exhibits enhanced T1 and T2 relaxation relative the iron poorer gray matter tissues (caudate nucleus and putamen) and also relative to the WM matter tissues (frontal WM and genu of the corpus callosum). We also observe that under riding this hypothesis-because we do not have independent confirmation-that iron caused relaxation enhancement, are the normal brain aging patterns, which suggest that the brain tissues become wetter with increasing age. Also noted is the virtual removal of age dependence observed for the T1/T2 ratio of WM tissues, further suggesting that this ratio may become of clinical significance in the diagnosis of neoplastic processes as well as for quantifying iron in tissue. The theoretical underpinnings of published brain iron Q-MRI techniques have been reviewed. We also examined MR relaxation theory essentials in relation to H-proton relaxation phenomena in diamagnetic tissues as well as theoretical extensions to describe relaxation effects in tissues containing iron deposits with a focus on ferritin. Also reported are in vivo Q-MRI results of 27 human brains obtained with a multispectral technique that uses the mixed turbo spin echo pulse sequence and a model conforming Q-MRI algorithms.


The efficacy of an additional cycle of oral steroids in partially recovered sudden sensorineural hearing loss (SSNHL) after initial oral steroid therapy.
There was no beneficial effect of an additional cycle of oral steroid therapy in partially recovered patients with sudden sensorineural hearing loss after initial oral steroid therapy. Partial recovery of hearing after one cycle of steroids might be the result of a relatively short duration of medication. We evaluated the efficacy of an additional cycle of steroids in those patients. With strict inclusion criteria, we selected the patients with hearing gain more than 10 dB, but still worse than 30 dB with hearing level, at the end of one cycle of steroid therapy. They were divided into a control group with no further treatment and a study group treated with an additional cycle of steroids. We compared their hearing outcomes, recovery rates and the mean duration of hearing improvement. We could not find any significant difference in either hearing outcomes, recovery rates or the mean duration of hearing improvement between the one-cycled group and the two-cycled group.


Interaction type of tetrabromobisphenol A and copper manipulates ammonia-oxidizing archaea and bacteria communities in co-contaminated river sediments.
The combined contamination of brominated flame retardants (BFRs) and heavy metals in electronic waste (e-waste) recycling and disposal areas has been a serious concern owing to their environmental persistence and chronic toxicities. Ammonia oxidizers, e.g., ammonia-oxidizing archaea (AOA) and bacteria (AOB) play essential roles in nitrogen cycling and can serve as ideal indicators that reflect the changes in sediment health in response to environmental variables. There is currently very little information available on the combined toxic effects of BFRs and heavy metals on AOA and AOB communities. In this study, two typical e-waste pollutants, tetrabromobisphenol A (TBBPA) and copper (Cu), were selected as target contaminants to investigate the individual and combined effects of both pollutants on AOA and AOB communities in river sediments. Respective treatments of TBBPA (1, 10, and 20 mg/kg wet weight), Cu (100 mg/kg wet weight) and their combined treatments (weight ratios of 1:100, 1:10, and 1:5) were performed in laboratory experiments. High-throughput sequencing was applied to explore the response of ammonia oxidizers to TBBPA and Cu. The interaction types of TBBPA and Cu were calculated by the directional classification system to reveal the individual and combined toxicities of both contaminants to the ammonia oxidizers. On days 15 and 30, the dominant interaction type of TBBPA and Cu was synergistic (62.50%), and the combined contamination exacted selective pressure and inhibition on the AOB and AOA communities. On days 45 and 90, the interaction type shifted to be antagonistic (83.33%), with both the AOB and AOA communities gradually reaching stable population equilibria. The alteration of the interaction type is attributed to the elevated TBBPA/Cu tolerance as the incubation time increased. This study disclosed the interaction types of TBBPA and Cu in contaminated river sediments, and revealed that the combined effect could potentially manipulate AOB and AOA communities.


[Correction of double-outlet right ventricle using the Kawashima intraventricular tunnel procedure].
Anatomical correction with an intraventricular tunnel, as suggested by Kawashima, was performed in 14 children with a double-outlet right ventricle and a subpulmonary (4) or non-committed (10) defect of the ventricular septum with one early and one late death. Nine children had previous palliative operations. Complications after radical surgery were residual ventricular defects (4), infectious endocarditis (2) and impaired rhythm (one sudden death). Twelve patients are after medium- term or long-term follow-up free from subjective complaints, ten children report good performance, in two the performance is slightly reduced. Anatomical intraventricular correction of double-outlet right ventricle restores the mitral valve and left ventricle to the systemic circulation. The prognosis of children with double-outlet right ventricle and subpulmonary or remote ventricular defect improves substantially.


Role of postoperative radiation therapy (PORT) in pT1-T2 N0 deep tongue cancers.
Carcinoma of tongue is associated with a high risk of occult metastasis and mortality despite early-stage detection and therapy; the critical tumor thickness at which this risk increases has been demonstrated as 4 mm or greater. There are no sufficient data in the published literature to evaluate the role of postoperative radiation therapy (PORT) in the treatment of pT1-T2 N0 oral tongue cancers with depth of invasion 4 mm or greater. Historical cohorts of patients with primary pT1-T2 N0 oral tongue cancer of depth of invasion 4 mm or greater treated surgically from January 2010 to December 2012 were included in the study, and negative margins on initial resection were filtered. Locoregional recurrence and death were analyzed among the patients who received PORT and those who did not. A total of 103 patients fulfilled the above-mentioned criteria, with 62 patients receiving PORT and 41 patients not receiving PORT; median period of follow-up was 41.3 months. Logistic and Cox regression models showed no significant difference in locoregional recurrences (P = .078) and survival (P = .339) between patients who received PORT and those who did not receive PORT. PORT did not influence survival of patients with stage I and stage II deep tongue cancers, with 4 mm or greater tumor invasion depth.


[Effect of Hydraulic Residence Time on Removal Efficiency of Pollutants in Subsurface Flow Constructed Wetlands and Analysis of Denitrification Mechanism].
This study used vertical and horizontal subsurface constructed wetlands with continuous inflow, to compare and analyze the effects of four hydraulic residence times on the removal efficiency of conventional pollutants. Using the optimal hydraulic retention time, the two types of wetlands were examined in terms of the stromal layer nitrification, denitrification, and ammonia oxidation abundance of functional genes, as well as the intensity of nitrification and denitrification. In addition, redundancy analysis and variance decomposition analysis were used to determine the main factors affecting nitrogen removal in the two kinds of wetlands, so that targeted improvement measures can be suggested. The best removal efficiency of conventional pollutants (COD, TP, TN, and NH4+-N) was achieved with a hydraulic retention time of 24 h, resulting in a removal rate of more than 70%. With a 24 h retention time, the removal rate of NH4+-N and TN and the intensity of nitrification and denitrification exhibited a gradually decreasing trend along the flow direction. Among the three functional genes, the abundance of denitrification functional genes (nirS) was much higher than that of nitrification functional genes (nxrA) and ammonia oxidation functional genes (AOB-amoA). In this study, the nitrogen removal ability of the two subsurface flow constructed wetlands was jointly affected by environmental factors and microbial factors, among which microbial factors contributed the most to nitrogen removal (55% and 48%). In addition, the removal rates of TN and NH4+-N were proportional to DO, specific surface area of substrate, COD concentration, as well as nitrification and denitrification functional genes, but inversely proportional to pH. Therefore, in order to improve the nitrogen removal efficiency of both systems, the amount of dissolved oxygen and carbon sources in the substrate layer should be increased, while the pH value should be appropriately reduced. Moreover, the horizontal subsurface constructed wetland significantly improves the nitrogen removal efficiency of the system, as the substrate layer has a larger specific surface area. This study provides a theoretical basis for the design of constructed wetlands and the selection of an optimal hydraulic residence time. Quantitative analysis of nitrogen removal pathways is of great significance for understanding the nitrogen removal mechanism and improving the nitrogen removal rate in constructed wetlands.


Healthcare provider perceptions and reported practices regarding opioid prescription for patients with chronic pain.
Data indicates that clinicians might be under-prescribing opioids for patients with chronic cancer pain, and this could impact adequate chronic pain management. Few studies have sought to understand healthcare provider (HCP) perceptions and practices regarding the prescription of opioids for chronic pain. We assessed HCP perceptions and practices regarding opioid prescription for patients with chronic pain since the onset of the COVID-19 pandemic. An anonymous cross-sectional survey was conducted among 186 HCPs who attended an opioid educational event in April 2021 and 2022. 61/143(44%) opioid prescribers reported reluctance to prescribe opioids for chronic pain. In a multivariate logistic model, younger participants (log OR -0.04, 95% CI: -0.085, -0.004; p = 0.033) and pain medicine clinicians (log OR -1.89, CI: -3.931, -0.286; p = 0.034) were less reluctant, whereas providers who worry about non-medical opioid use (NMOU) were more reluctant to prescribe opioids (log OR 1.58 95% CI: 0.77-2.43; p < 0.001). 53/143(37%) respondents had experienced increased challenges regarding opioid dispensing at pharmacies, and 84/179(47%) reported similar experience by their patients. 54/178(30%) HCPs were aware of opioid-related harmful incidents to patients or their families, including incidents attributed to opioid misuse by a household or family member. A significant number of opioid prescribers were reluctant to prescribe opioids for patients with chronic pain. Many reported challenges regarding dispensing of opioids at the pharmacies. These may be unintended consequences of policies to address the opioid crisis. Future measures should focus on addressing regulatory barriers without undermining the gains already made to combat the opioid crisis.


Vestibular stimulation for management of premenstrual syndrome.
The present study was undertaken to observe the effectiveness of vestibular stimulation in the management of premenstrual syndrome (PMS). The present study was an experimental study; twenty female participants of age group 18-30 years were recruited in the present study. Conventional swing was used to administer vestibular stimulation. Variables were recorded before and after vestibular stimulation and compared. Depression and stress scores are significantly decreased after 2 months of intervention. Anxiety scores decreased followed by vestibular stimulation. However, it is no statistically significant. Serum cortisol levels significantly decreased after 2 months of intervention. WHOQOL-BREF-transformed scores were not significantly changed followed by the intervention. However, psychological domain score (T2) and social relationships domain score (T3) were increased followed by intervention. Systolic blood pressure was significantly decreased after 2 months of intervention. No significant change was observed in diastolic pressure and pulse rate. Pain score was significantly decreased after 2 months of intervention. Mini mental status examination scores and spatial and verbal memory score were significantly improved followed by intervention. The present study provides preliminary evidence for implementing vestibular stimulation for management of PMS as a nonpharmacological therapy. Hence, we recommend further well-controlled, detailed studies in this area with higher sample size.


[Analysis of parameters for the equation of isotherms of chemical modification for the alkylation of nucleic acids in complexes with chloroethylmethylaminobenzylidene oligonucleotides].
The coincidence between the adsorbtion isotherm E + X in equilibrium or formed from EX (association constant KX) and isotherm of the chemical modification (the dependence of the limit extent of modification r infinity biopolymer E with excess of the reagent X) calculated earlier. Schemes (1) and (2) are given. It was shown that r infinity is identical to [EX]0/e), if (1) and (2-2) are absent due to equality of the rate constants of the conversion of X in complex and in solution, i.e. the isotherm of modification may imitate the adsorbtion isotherm. The influence of the equilibrium (2) at the initial part of the isotherm of modification is not essential, if process (1-1) is absent and y2 = k -P/k1 is small (smaller than or equal to 0.1) and y1 = (k1/k2)(kP/k-PKX) has various magnitudes within y1 x y2 smaller than or equal to 0.1. Once the parameter y1 is equal to unity, the difference between the isotherms of adsorbtion and of modification are small at the initial part in spite of equilibrium (1-1). These results indicate the KX may be calculated from the modification data given earlier in the found range of values of parameters y1 and y2, if e0 is determined by an independent way.


The value of open access and a patient centric approach to oral oncolytic utilization in the treatment of Chronic Myelogenous Leukemia: A U.S. perspective.
Since the introduction of tyrosine kinase inhibitors (TKIs), the treatment of patients with chronic myelogenous leukemia (CML) has resulted in significant improvement in patient survival but at a higher pharmaceutical cost to payers. The recent introduction of generic imatinib presents an opportunity to lower pharmacy costs within a population that is growing due to improved survival. Recent literature has focused on the likely benefits to payers of step therapy through generic imatinib. Areas covered: This review provides a perspective that is broader than the evaluation of financial savings or narrowly defined health economic metrics by incorporating factors such as CML patient heterogeneity, including varying levels of disease progression risk, comorbidities and genetic mutation status, differences in TKI product profiles, clinical guideline recommendations, and the importance of individualized patient care. A focused literature review evaluating the real-world impact of utilization management programs is presented. Expert commentary: The findings indicate that payers can achieve substantial savings without the need to implement utilization management policies. Compromises in the ability to provide individualized patient care and unwanted economic consequences resulting from increased costs of disease progression, adverse events, and lack of response to treatment due to utilization management are summarized.


A novel approach to quantify metrics of upwelling intensity, frequency, and duration.
The importance of coastal upwelling systems is widely recognized. However, several aspects of the current and future behaviors of these systems remain uncertain. Fluctuations in temperature because of anthropogenic climate change are hypothesized to affect upwelling-favorable winds and coastal upwelling is expected to intensify across all Eastern Boundary Upwelling Systems. To better understand how upwelling may change in the future, it is necessary to develop a more rigorous method of quantifying this phenomenon. In this paper, we use SST data and wind data in a novel method of detecting upwelling signals and quantifying metrics of upwelling intensity, duration, and frequency at four sites within the Benguela Upwelling System. We found that indicators of upwelling are uniformly detected across five SST products for each of the four sites and that the duration of those signals is longer in SST products with higher spatial resolutions. Moreover, the high-resolution SST products are significantly more likely to display upwelling signals at 25 km away from the coast when signals were also detected at the coast. Our findings promote the viability of using SST and wind time series data to detect upwelling signals within coastal upwelling systems. We highlight the importance of high-resolution data products to improve the reliability of such estimates. This study represents an important step towards the development of an objective method for describing the behavior of coastal upwelling systems.


Non-functioning Pituitary Macroadenoma Resection in Twin Pregnancy: A Case Report.
Non-functioning pituitary adenomas (NFPAs) are rare in females of reproductive age. We present the case of a 37-year-old pregnant woman in her second trimester with a diagnosis of symptomatic pituitary macroadenoma with twin pregnancy. Magnetic resonance imaging (MRI) confirmed a well-defined macroadenoma compressing the optic chiasm, thus necessitating surgery. The patient underwent transnasal transsphenoidal resection of the tumor under general anesthesia. Anesthesia management posed challenges due to concurrent considerations of pregnancy and neurosurgery. Induction, maintenance, monitoring, and fluid management were carefully performed. The patient experienced a transient decrease in oxygen saturation, which improved with lung recruitment maneuvers. The surgery was successful without any complications. Postoperatively, an ophthalmology consultation was done, which showed an improvement in the patient's vision, as evidenced by the perimetry findings. Later, she delivered healthy twins at 36 weeks and six days of gestation. This case highlights the importance of a multidisciplinary approach and meticulous anesthetic management when dealing with pregnant patients undergoing non-obstetric surgery, ensuring optimal maternal-fetal perfusion and minimizing risks to both the mother and the fetus.


Photothermal spectroscopy of scattering media.
We present a general unified theoretical analysis of the role of scattering in photothermal spectroscopy, e.g., photoacoustic and photothermal deflection. We show that while the photothermal signal is significantly affected in the case of highly scattering media, it is independent of scattering for optically thin samples. Numerical estimates of the scattering contribution and comparison with experimental results are given. We also elucidate the relationship between photothermal and diffuse reflectance spectroscopies.


Targeting SLC7A11 specifically suppresses the progression of colorectal cancer stem cells via inducing ferroptosis.
Recent studies have revealed the critical roles of ferroptosis in different physiological and pathological processes, however, its effects on the progression of colorectal cancer stem cells (CSCs) are still unclear. Here, we found that colorectal CSCs exhibited a remarkably lower level of reactive oxygen species (ROS), a higher level of cysteine, glutathione and SLC7A11 compared to colorectal cancer cells. Knockout of SLC7A11 increased the ROS level and reduced the levels of cysteine and glutathione, subsequently attenuating the viability of colorectal CSCs. Erastin, an inhibitor of SLC7A11, was found to hold a remarkably stronger cytotoxic effect on colorectal CSCs via in vitro and in vivo experiments. Finally, it was found that Erastin attenuated the chemoresistance of colorectal CSCs. This work indicates that colorectal CSCs are more sensitive to ferroptosis, which could be targeted to attenuate colorectal cancer progression and chemoresistance.


Influence of Acute Mental Arithmetic Stress on Taste and Pungency.
Mental stress is a known risk factor for disease. This study investigated changes in sensations of taste and pungency before and after mental stress. Thirty healthy male university students rested for 20 min, performed mental arithmetic tasks for 10 min, and then underwent measurement of changes in their taste and ability to discern pungency. Taste was measured with the "Taste Disk®," and pungency was measured by a filter-paper disc method using capsaicin solution. Subjects were not told the order of the reagent solutions used. To quantify pain sensation, a weak current applied to the central inner forearm skin by a Pain Vision® quantitative pain sensation analyzer was gradually increased. The degree of stress was measured by portable electrocardiography (ECG). During mental stress, the cognitive threshold of salty taste, sweet taste, and bitterness was significantly decreased, whereas the sensations of pungency and forearm skin pain were increased and showed significant correlation. Based on sympathetic nerve activity analyzed with the ECG, the subjects were divided into the mental stress group and non-mental stress group. The mental stress group experienced an increase in the pungency threshold and sensation of forearm skin pain with significantly high correlations obtained, whereas no correlation was found between these factors in the non-mental stress group. Acute mental stress increased the sensitivity to taste but decreased the sensitivity to the sensation of pungency on the tongue and pain on the skin. Sympathetic activity activated by stress may affect taste and the sensation of pungency.


Dual-Mode Based Sliding Mode Control Approach for Nonlinear Chemical Processes.
This paper synthesizes a new sliding mode controller (SMC) approach to enhance tracking and regulation tasks by following dual-mode concepts. The new control law consists of two distinct types of operation, using the combination of higher gain to large error signals (transient) and lower gain to small error signals (the region around the set point). The design is presented from a dual-mode (PD-PID) sliding surface operating in concert, fulfilling desired control objectives to ensure stability and performance. Therefore, a new controller was established, and we called it a dual-mode based SMC. The proposed controller is tested by computer simulations applied to two nonlinear processes, a continuous stirred-tank reactor (CSTR) and a mixing tank with a variable dead time. The results are compared with two different alternatives of SMC. In addition, the merits and drawbacks of the control schemes are analyzed using radial graphs, comparing the control methods with various performance measures for set points and disturbances changes. The ITSE (integral of time multiplied by the squared error), TVu (total variation of control effort) indices, Mp (maximum overshoot), and ts (settling time) were the indices used for performance analysis and comparisons.


Fat mass and obesity-associated gene (FTO) is associated to eating disorders susceptibility and moderates the expression of psychopathological traits.
Eating Disorders (EDs) show a multifactorial etiopathogenesis including environmental, psychological and biological factors. In the present study, we propose a model of interactions between genetic vulnerability-represented by Fat Mass and Obesity-Associated (FTO) gene-and stable psychopathological traits, such as bodily disorders and emotion dysregulation for EDs patients. The distribution of a polymorphism of the FTO (rs9939609 T>A) was evaluated in a series of 250 EDs patients and in a group of 119 healthy control subjects. Clinical data were collected through a face-to-face interview and several self-reported questionnaires were applied, including the Emotional Eating Scale and the IDentity and EAting disorders (IDEA) questionnaire for bodily disorders and self-identity. The A-allele was associated with an increased vulnerability to EDs (AA+AT genotypes frequency 72.8% in EDs vs. 52.9% in controls). The presence of the A-allele was associated with binge eating behavior, higher emotional eating and higher IDEA scores. Finally, the FTO rs9939609 SNP was found to influence the relationship between these variables, as an association between disorder of corporeality and emotional eating was found only in A-allele carriers. A-allele seems to represent a potential additive risk factor for EDs persons, with bodily disorders to develop emotional eating and binge eating behaviors.


C18-Diterpenoid alkaloids from Delphinium anthriscifolium var. majus.
Five new C18-diterpenoid alkaloids, anthriscifoltines C-G (1-5), along with four known diterpenoid alkaloids anthriscifolcines C-F (6-9), were isolated from the extract of Delphinium anthriscifolium var. majus. Their structures were elucidated by extensive spectroscopic analyses (including 1D-, 2D-NMR, and HR-ESI-MS). Compounds 1-5 were also evaluated for their cytotoxic activity against MCF-7, HepG2, and H460 human cancer cell lines.


Image of the Month: Concomitant Tricuspid and Mitral Native Valve Infective Endocarditis.
A 33-year-old immunocompetent man was admitted to the authors' hospital with a one-month duration of fevers, chills, and non-productive coughs, and suddenonset weakness and ischemic pain of both lower extremities. Physical examination revealed crepitating rales heard over bilateral lung fields. On auscultation, a grade 2~3/6 systolic murmur was heard over the leftlower sternal border and apical area. Transthoracic echocardiography revealed a mobile mass on the tricuspid valve compatible with vegetation, in addition to concomitant mitral valve vegetation (Video 1). Thoracic computed tomography (CT) with contrast revealed cavitary lesions of the left and right lung fields (Fig. 1A and B). Abdominal CT showed a splenic infarction (Fig. 2A), a renal infarction (Fig. 2B), and thromboembolic occlusion of the distal aorta and right common iliac artery (Fig. 3). The patient denied any history of intravenous drug abuse. Blood cultures grew Streptococcus agalactiae (penicillin G-sensitive with a minimal inhibitory concentration ≤0.06 μg/ml). Video 1: Transthoracic echocardiography showing mobile masses on tricuspid and mitral valves compatible with vegetation on the apical four-chamber view.


Distal pancreatectomy in chronic pancreatitis.
The indications for a resective procedure in chronic pancreatitis are severe pain and local complications. The aim of this study, based on prospectively assessed data, was to evaluate distal pancreatectomy in patients suffering from chronic pancreatitis localized in the corpus and cauda of the pancreatic gland. Seventy-four patients undergoing distal pancreatectomy were evaluated pre- and postoperatively (after a median observation period of 58 months) for pain, professional status, alcohol consumption, and endocrine function as measured by the glucose tolerance test preoperatively. The indication for operation was severe therapy-resistant pain in nearly all patients and an inflammatory tumor or pancreatic pseudocysts in over 50% of the patients. One fourth of the patients were operated in order to exclude malignancy. Ninety-five percent of the patients underwent distal pancreatectomy, only in 4 cases (5%) was a subtotal (Child) resective procedure performed. In 34% of patients undergoing distal pancreatectomy a splenectomy could be avoided. The early postoperative complications were few and mostly due to the severe comorbidity of the patients. During the median observation period of 58 months 14.7% of the patients died due to diseases not related to distal pancreatectomy. Six percent of the patients could not be reevaluated and were lost to follow-up. In the remaining 59 patients 88% had significantly less pain and 66% had an increase in median body weight of 8 kg. Fifty percent of the patients had full or partial professional rehabilitation, one fourth was unemployed and 24% had retired due to age. 51.7% had a normal endocrine function as assessed by the glucose tolerance test, 16.2 and 21.6% had a latent or manifest diabetes mellitus, respectively. In 74.5% of all patients the endocrine function did not worsen during the observation period. In comparison to conservative treatment distal pancreatectomy is a suitable therapeutic measure in patients with severe pain and local complications. It significantly improves the quality of life of patients without compromising endocrine function. Postoperative lethality is lower than in conservatively treated patients and is not related to distal pancreatectomy.


Breast feeding initiation rate across Western countries: does religion matter? An ecological study.
Breast feeding initiation rates remain below 80% in some Western countries. Many individual-level determinants are known; however, less is known regarding cultural and societal determinants, such as religion, that could explain population-level variations. We examined the correlations of the proportions of Catholics and Protestants with the breast feeding initiation rates across and within Western countries. Using publicly available data, we carried out an ecological study comparing the proportions of Catholics and Protestants with the rates of breast feeding initiation. We correlated data at the country level, and additionally explored within-country data in five Western countries: France (Departments), Ireland (counties), the UK (countries), Canada (provinces) and the USA (states). Our analyses accounted for human development index, gross domestic product and population density. We observed a negative correlation (r=-0.30) between the proportion of Catholics and the rate of breast feeding initiation in Western countries. This correlation was consistent when using within-country data in France (r=-0.27), Ireland (r=-0.23), the UK (r=-0.79) and Canada (r=-0.62). In the USA, the positive correlation (r=0.26) between a state's proportion of Catholics and its breast feeding initiation rate was confounded by race, education and socioeconomic status (SES). After controlling for education and SES, the state proportion of non-Hispanic white Catholics was negatively correlated (r=-0.29) with the rate of breast feeding initiation. In this ecological study, we found consistent negative correlations between Catholicism and breast feeding initiation rates. Qualitative and quantitative studies at the individual level are needed to confirm and explain our findings. Our results suggest that women living in a country or region where Catholicism has historically dominated are less likely to initiate breast feeding, and that breast feeding promotion policies should be adapted to better fit populations' cultural and religious norms.


Anxiety disorders in primary care: a life-span perspective.
From a family-oriented life-span perspective, the authors highlight issues involved in recognition, assessment, and treatment of anxiety disorders. After reviewing prevalence rates for these disorders in child, adult, and geriatric groups, they discuss cross-generational transmission of illness and identify cross-cutting themes, such as comorbidity of anxiety and depression, relationship between anxiety disorders and quality of life, and links among disability, adversity, and anxiety. They also discuss issues specific to childbearing, motherhood, and bereavement, and conclude with a brief summary of treatment approaches.


Nutritional and physiologic significance of alpha-lactalbumin in infants.
alpha-Lactalbumin is the major protein in breast milk (20-25% of total protein) and has been described to have several physiologic functions in the neonatal period. In the mammary gland, it participates in lactose synthesis, thereby creating an osmotic "drag" to facilitate milk production and secretion. alpha-Lactalbumin binds divalent cations (Ca, Zn) and may facilitate the absorption of essential minerals, and it provides a well-balanced supply of essential amino acids to the growing infant. During its digestion, peptides appear to be transiently formed that have antibacterial and immunostimulatory properties, thereby possibly aiding in the protection against infection. A novel folding variant ("molten globule state") of multimeric alpha-lactalbumin has recently been discovered that has anti-infective activity and enhances apoptosis, thus possibly affecting mucosal cell turnover and proliferation. Cow milk also contains alpha-lactalbumin, albeit less than human milk (2-5% of total protein in bovine milk), and protein fractions enriched with alpha-lactalbumin may now be added to infant formula to provide some of the benefits of human alpha-lactalbumin.


Chromosome 18q22.2-->qter deletion and a congenital anomaly syndrome with multiple vertebral segmentation defects.
Multiple vertebral segmentation defects occur in a group of conditions variably associated with anomalies of other organ systems. This report describes a female child in whom a deletion of chromosome 18 (18q22.2-->qter) is associated with congenital anomalies including multiple vertebral segmentation defects resembling sporadic spondylocostal dysplasia. The child also has unilateral renal agenesis and unilateral fibular aplasia. The association of severe multiple vertebral segmentation defects with 18q- in this patient suggests the possibility that a gene important for somite formation or vertebral differentiation maps to this segment of chromosome 18.


Virotherapy with a type 2 herpes simplex virus-derived oncolytic virus induces potent antitumor immunity against neuroblastoma.
We recently constructed an oncolytic virus from type 2 herpes simplex virus (HSV-2) that selectively targets and kills tumor cells with an activated Ras signaling pathway. Designated FusOn-H2, this virus has shown several discrete killing mechanisms. Here, we evaluated the antitumor immune responses after FusOn-H2-mediated virotherapy in a syngeneic murine neuroblastoma model. We directly injected FusOn-H2 into established tumors and then measured its antitumor effect and the accompanying tumor-specific immune responses. Several oncolytic HSVs constructed from HSV-1 were included in the same experiments for comparisons. Our data show that tumor destruction by FusOn-H2 in vivo induces potent antitumor immune responses in this syngeneic neuroblastoma model. The elicited cellular immunity not only eradicated neuroblastoma cells in vitro but also inhibited the growth of tumors at sites distant from the virus injection site. Moreover, adoptive transfer of splenocytes from mice receiving virotherapy to naïve mice resulted in a measurable antitumor effect. We conclude that the ability of FusOn-H2 to induce tumor-specific cellular immunity expands the oncolytic repertoire of this virus and increases the likelihood that its use in patients would produce significant therapeutic benefits.


Gyejigachulbu-Tang Relieves Oxaliplatin-Induced Neuropathic Cold and Mechanical Hypersensitivity in Rats via the Suppression of Spinal Glial Activation.
Activation of spinal glial cells plays a crucial role in the pathogenesis of neuropathic pain. An administration of oxaliplatin, an important anticancer drug, often induces acute neuropathic cold hypersensitivity and/or mechanical hypersensitivity in patients. Gyejigachulbu-tang (GBT), a herbal formula comprising Cinnamomi Cortex, Paeoniae Radix, Atractylodis Lanceae Rhizoma, Zizyphi Fructus, Glycyrrhizae Radix, Zingiberis Rhizoma, and Aconiti Tuber, has been used in East Asia to treat various pain symptoms, especially in cold patients. This study investigated whether and how GBT alleviates oxaliplatin-induced cold and mechanical hypersensitivity in rats. The behavioral signs of cold and mechanical hypersensitivity were evaluated by a tail immersion test in cold water (4°C) and a von Frey hair test, respectively. The significant cold and mechanical hypersensitivity were observed 3 days after an oxaliplatin injection (6 mg/kg, i.p.). Daily oral administration of GBT (200, 400, and 600 mg/kg) for 5 days markedly attenuated cold and mechanical hypersensitivity. Immunoreactivities of glial fibrillary acidic protein (GFAP, astrocyte marker) and OX-42 (microglia marker) in the spinal dorsal horn were significantly increased by an oxaliplatin injection, which were restored by GBT administration. These results indicate that GBT relieves oxaliplatin-induced cold and mechanical hypersensitivity in rats possibly through the suppression of spinal glial activation.


Error reduction in the New World. How we can improve the level of safety for everyone in our operating rooms.
In order to do no harm, ask yourself and your colleagues the following questions: Is our environment safe? Does staff follow all safety measures? Do physicians and visitors follow safety rules? Is every staff member aware of their role in safety for all? Is there an effective staff/leader safety inspection team in place and functioning effectively? Are all reasonable recommendations implemented? Have the errors been reviewed in detail? If so, what were the results and what changes were made? Is self-reporting encouraged without repercussions? Do you know what your error rates are, what the root causes were, which systems were lacking, and how they have been modified? Needless to say we have a great deal of work to do and many challenges to overcome if we are to decrease our risk of error. But where to start? Do a critical analysis of the current system and, on a daily basis, focus on improving some small piece of the safety network that will have a lasting impact. The commitment and participation of staff, strong visible leadership, and accountable, well-trained individuals and teams will all be major contributors to a safe environment.


The enhanced monocyte adhesiveness after UVB exposure requires ROS and NF-kappaB signaling in human keratinocyte.
The infiltration of both monocyte and activated T cells in the skin is one of critical steps in the development of UVB-induced inflammation. Upregulation of adhesion molecules such as intercellular adhesion molecule 1 (ICAM-1) on the surface of keratinocytes plays an important role in this process. In this study, we examined the molecular mechanism responsible for UVB-induced expression of ICAM-1 and subsequent monocyte adhesion by keratinocyte. We observed that (1) UVB induced protein and mRNA expression of ICAM-1 in a dose- and time-dependent manner in human keratinocyte cell HaCaT; (2) UVB induced the translocation of NF-kappaB and inhibition of NF-kappaB by NF-kappaB inhibitors suppressed UVB-induced mRNA and protein expression of ICAM-1; (3) UVB increased the intracellular level of reactive oxygen species (ROS) by HaCaT cells; (4) UVB-induced increase of intracellular ROS level was suppressed by pretreatment with diphenyl iodonium (DPI) and N-acetyl cysteine (NAC); and (5) inhibition of UVB-induced ROS production by DPI or NAC suppressed UVB-mediated translocation of NF-kappaB, expression of ICAM-1 and subsequent monocyte adhesion in HaCaT cells. These results suggest that UVB-induced ROS is involved in the translocation of NF-kappaB which is responsible for expression of ICAM-1 and subsequent increased monocyte adhesion in human keratinocyte.


Homeobox Transcription Factors Are Required for Fungal Development and the Suppression of Host Defense Mechanisms in the Colletotrichum scovillei-Pepper Pathosystem.
Colletotrichum scovillei, an ascomycete phytopathogenic fungus, is the main causal agent of serious yield losses of economic crops worldwide. The fungus causes anthracnose disease on several fruits, including peppers. However, little is known regarding the underlying molecular mechanisms involved in the development of anthracnose caused by this fungus. In an initial step toward understanding the development of anthracnose on pepper fruits, we retrieved 624 transcription factors (TFs) from the whole genome of C. scovillei and comparatively analyzed the entire repertoire of TFs among phytopathogenic fungi. Evolution and proliferation of members of the homeobox-like superfamily, including homeobox (HOX) TFs that regulate the development of eukaryotic organisms, were demonstrated in the genus Colletotrichum. C. scovillei was found to contain 10 HOX TF genes (CsHOX1 to CsHOX10), which were functionally characterized using deletion mutants of each CsHOX gene. Notably, CsHOX1 was identified as a pathogenicity factor required for the suppression of host defense mechanisms, which represents a new role for HOX TFs in pathogenic fungi. CsHOX2 and CsHOX7 were found to play essential roles in conidiation and appressorium development, respectively, in a stage-specific manner in C. scovillei. Our study provides a molecular basis for understanding the mechanisms associated with the development of anthracnose on fruits caused by C. scovillei, which will aid in the development of novel approaches for disease management. IMPORTANCE The ascomycete phytopathogenic fungus, Colletotrichum scovillei, causes serious yield loss on peppers. However, little is known about molecular mechanisms involved in the development of anthracnose caused by this fungus. We analyzed whole-genome sequences of C. scovillei and isolated 624 putative TFs, revealing the existence of 10 homeobox (HOX) transcription factor (TF) genes. We found that CsHOX1 is a pathogenicity factor required for the suppression of host defense mechanism, which represents a new role for HOX TFs in pathogenic fungi. We also found that CsHOX2 and CsHOX7 play essential roles in conidiation and appressorium development, respectively, in a stage-specific manner in C. scovillei. Our study contributes to understanding the mechanisms associated with the development of anthracnose on fruits caused by C. scovillei, which will aid for initiating novel approaches for disease management.


DruMAP: A Novel Drug Metabolism and Pharmacokinetics Analysis Platform.
We developed a novel drug metabolism and pharmacokinetics (DMPK) analysis platform named DruMAP. This platform consists of a database for DMPK parameters and programs that can predict many DMPK parameters based on the chemical structure of a compound. The DruMAP database includes curated DMPK parameters from public sources and in-house experimental data obtained under standardized conditions; it also stores predicted DMPK parameters produced by our prediction programs. Users can predict several DMPK parameters simultaneously for novel compounds not found in the database. Furthermore, the highly flexible search system enables users to search for compounds as they desire. The current version of DruMAP comprises more than 30,000 chemical compounds, about 40,000 activity values (collected from public databases and in-house data), and about 600,000 predicted values. Our platform provides a simple tool for searching and predicting DMPK parameters and is expected to contribute to the acceleration of new drug development. DruMAP can be freely accessed at: https://drumap.nibiohn.go.jp/.


Intimate partner violence and women with disabilities: toward bringing visibility to an unrecognized population.
Although women with disabilities experience abuse at alarming rates, research exploring the unique experiences and the dimensions of intimate partner violence (IPV) in the lives of women with disabilities is in its infancy. This article attempts to highlight multidimensional factors for consideration in addressing the needs of women with disabilities who are victims of abuse and violence. Risk factors related to the vulnerability that disabilities pose for IPV victimization are explored in relation to consequent limitations of the traditional models of domestic violence. Feminist disability theory as a viable theory for framing meaningful research and informing effective and accessible prevention and intervention for women with disabilities who are victims of IPV is introduced.


The Impact of Comorbidity Burden on Complications, Length of Stay, and Direct Hospital Costs After Minimally Invasive Transforaminal Lumbar Interbody Fusion.
A retrospective cohort. The aim of this study was to determine whether comorbidity as determined by Charlson Comorbidity Index (CCI) is associated with inpatient complication rate, length of stay (LOS), or direct hospital costs after minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF). In the spine literature, comorbidity burden has been associated with an increased risk for complications, prolonged LOS, and greater hospital costs. Few studies have investigated the influence of comorbidity burden on these outcomes in minimally invasive spine surgery populations. A prospectively maintained surgical registry of patients undergoing primary, single-level MIS-TLIF was retrospectively reviewed. Patients were stratified by CCI and tested for association with preoperative demographics and perioperative characteristics using Chi-squared analysis or one-way analysis of variance for categorical and continuous variables, respectively. Complication rates, LOS, and direct hospital costs were compared between groups using a one-way analysis of variance. Two hundred ninety-eight patients were included. About 19.8% had a CCI of 0, 41.3% had a CCI of 1 to 2, 27.2% had a CCI of 3 to 4, and 11.7% had a CCI ≥ 5. Elevated CCI was associated with older age, smoking, and insurance status. Elevated CCI was significantly associated with a greater total inpatient complication rate. Regarding LOS and total direct hospital costs, there were no associations identified. However, elevated CCI was associated with greater costs accrued in the intensive care unit, laboratory costs, and cardiology-related costs. Greater comorbidity burden as reflected by higher CCI was associated with increased postoperative complication rates following primary, single-level MIS-TLIF. However, this did not lead to prolongations in hospital stay or increased total direct hospital costs. This lack of association may suggest that the limited tissue trauma and operative exposure utilized in minimally invasive approaches may limit the utility of CCI as a predictor of surgical outcomes and costs. 4.