Effects of Magnesium on Intact Chloroplasts : II. CATION SPECIFICITY AND INVOLVEMENT OF THE ENVELOPE ATPase IN (SODIUM) POTASSIUM/PROTON EXCHANGE ACROSS THE ENVELOPE.
Addition of exogenous Mg(2+) (2 millimolar) to illuminated intact spinach (Spinacia oleracea L.) chloroplasts caused acidification of the stroma and a 20% decrease in stromal K(+). Addition of K(+) (10-50 millimolar) reversed both stromal acidification and K(+) efflux from the chloroplast caused by Mg(2+). These data suggested that Mg(2+) induced reversible H(+)/K(+) fluxes across the chloroplast envelope. Ca(2+) and Mn(2+) (2 millimolar) were as effective as 4 millimolar Mg(2+) in causing K(+) efflux from chloroplasts and inhibition of O(2) evolution. In contrast, 10 millimolar Ba(2+) induced only a small amount of inhibition. The lack of strong inhibition by Ba(2+) indicated that the effects of divalent cations such as Mg(2+) cannot be attributed to generalized electrostatic interactions of the cation with the chloroplast envelope. With the chloroplasts used in this study, stromal acidification caused by 2 millimolar Mg(2+) was small (0.07 to 0.15 pH units), but sufficient to account for the inhibition of O(2) evolution (43%) induced by Mg(2+).A variety of ATPase inhibitors were tested for effects on Mg(2+)-induced H(+)/K(+) fluxes. Oligomycin was the only ATPase inhibitor which specifically inhibited photosynthesis in the presence of Mg(2+) + K(+), but had little or no effect in the absence of these cations. In the presence of oligomycin, much higher concentrations (50 millimolar) of exogenous K(+) were required to reverse Mg(2+)-induced acidification and inhibition of O(2) evolution than in its absence. Oligomycin (in the absence of divalent cations) increased the inhibition of photosynthesis caused by sodium acetate, which acts by causing stromal acidification. In addition, the chloroplast envelope ATPase was inhibited partially (45%) by oligomycin. These results suggested that H(+) fluxes across the chloroplast envelope are regulated by two mechanisms: (a) an active, oligomycin-sensitive H(+) efflux and (b) a reversible, Mg(2+)-dependent, oligomycin-insensitive H(+)/K(+) exchange.


Emergency department security: a call for reassessment.
Numerous articles tell of the security breaches hospital emergency rooms face on a daily basis. The recent events of September 11 th have further complicated these breaches, and have shed new light on previously ignored issues surrounding bioterrorism. In previous disaster scenarios there has been a "script" to follow; however bioterrorism follows no script and presents a host of new security issues. Successful delineation of the characteristics of bioterrorist weapons is only the first step in dealing with such a scenario, and will set into motion a series of events seen only on small levels in the past.


Smooth-muscle progenitor cells isolated from patients with moyamoya disease: novel experimental cell model.
Moyamoya disease (MMD) is a cerebrovascular occlusive disease affecting bilateral internal carotid termini. Smooth-muscle cells are one of the major cell types involved in this disease process. The characteristics of circulating smooth-muscle progenitor cells (SPCs) in MMD are poorly understood. The authors purified SPCs from the peripheral blood of patients with MMD and sought to identify differentially expressed genes (DEGs) in SPCs from these patients. The authors cultured and isolated SPCs from the peripheral blood of patients with MMD (n = 25) and healthy control volunteers (n = 22). After confirmation of the cellular phenotype, RNA was extracted from the cells and DEGs were identified using a commercially available gene chip. Real-time quantitative reverse transcription polymerase chain reaction was performed to confirm the putative pathogenetic DEGs. The SPC-type outgrowth cells in patients with MMD invariably showed a hill-and-valley appearance under microscopic examination, and demonstrated high α-smooth muscle actin, myosin heavy chain, and calponin expression (96.5% ± 2.1%, 42.8% ± 18.6%, and 87.1% ± 8.2%, respectively), and minimal CD31 expression (less than 1%) on fluorescence-activated cell sorter analysis. The SPCs in the MMD group tended to make more irregularly arranged and thickened tubules on the tube formation assay. In the SPCs from patients with MMD, 286 genes (124 upregulated and 162 downregulated) were differentially expressed; they were related to cell adhesion, cell migration, immune response, and vascular development. With adequate culture conditions, SPCs could be established from the peripheral blood of patients with MMD. These cells showed specific DEGs compared with healthy control volunteers. This study provides a novel experimental cell model for further research of MMD.


Granular cell tumor of the esophagus.
Granular cell tumor (GCT) of the esophagus is a rarely-met-with neoplasm. It is almost invariably benign in character and is of still-disputed histogenesis. Small lesions are asymptomatic. Those over 1 cm in diameter may be accompanied by painful swallowing or retrosternal discomfort. Local resection is the treatment of choice for lesions that are accompanied by symptoms, or that are larger than 1 cm. A tumor incidentally encountered in an asymptomatic patient may be safely followed endoscopically. A successful endoscopic removal of such a lesion is described.


Transtubal spread of endometrial carcinoma: correlation of intra-luminal tumour cells with tumour grade, peritoneal fluid cytology, and extra-uterine metastasis.
To assess the significance of intra-luminal tumour cells (ILTC) within the fallopian tubes of patients with endometrial carcinoma, with emphasis on high grade histological subtypes. Complete histological examination of fallopian tube tissue was performed in 36 low grade endometrioid adenocarcinomas and in a consecutive series of 226 high grade endometrial malignancies including 92 serous carcinomas, 64 grade 3 endometrioid carcinomas, 26 carcinosarcomas, 25 undifferentiated/dedifferentiated carcinomas, and 19 clear cell carcinomas. The presence of ILTC was correlated with peritoneal fluid cytology, histologically confirmed peritoneal tumour spread, and lymph node metastases. ILTC were identified in 26% and 3% of high and low grade carcinomas, respectively. The presence of ILTC correlated strongly with positive peritoneal fluid cytology and with peritoneal metastasis in high grade tumours (both p < 0.001), and there was also a correlation with lymph node metastasis (p = 0.049). ILTC were more common in serous and undifferentiated carcinomas (>30%) but the differences between the high grade tumour subtypes were not statistically significant. These findings suggest that ILTC associated with high grade endometrial cancers have the capacity to implant and invade the peritoneal cavity. Positive cytology in such cases may be more significant than in low grade tumours. Complete tubal examination may provide additional prognostic information in high grade endometrial carcinoma.


Dust Aerosol Detection by the Modified CO₂ Slicing Method.
Dust aerosols, which have diverse and strong influences on the environment, must be monitored. Satellite data are effective for monitoring atmospheric conditions globally. In this work, the modified CO₂ slicing method, a cloud detection technique using thermal infrared data from space, was applied to GOSAT data to detect the dust aerosol layer height. The results were compared using lidar measurements. Comparison of horizontal distributions found for northern Africa during summer revealed that both the relative frequencies of the low level aerosol layer from the slicing method and the dust frequencies of CALIPSO are high in northern coastal areas. Comparisons of detected layer top heights using collocated data with CALIPSO and ground-based lidar consistently showed high detection frequencies of the lower level aerosol layer, although the slicing method sometimes produces overestimates. This tendency is significant over land. The main causes of this tendency might be uncertainty of the surface skin temperature and a temperature inversion layer in the atmosphere. The results revealed that obtaining the detailed behavior of dust aerosols using the modified slicing method alone is difficult.


Suppression of lymphocytic choriomeningitis virus--induced growth hormone deficiency syndrome by disease-negative virus variants.
Populations of RNA viruses consist of heterogeneous mixtures of related genomes (quasispecies). Isolation of variants present at low levels within a population can result in clonal virus populations which display markedly different phenotypes upon infection of the host. The mechanisms by which these variants are maintained within the original quasispecies are not understood. Certain strains of lymphocytic choriomeningitis virus (LCMV) cause a growth hormone deficiency syndrome (GHDS) when inoculated into newborn C3H/St mice while others do not. We have previously described the isolation of virus clones from the GHDS-negative WE strain of LCMV which differ in their ability to cause GHDS. To investigate how disease-positive clones can remain hidden within a disease-negative parental population, we examined whether infection with mixtures of the GHDS-negative (WE c54) and GHDS-positive (WE c2.5) clones could cause GHDS. Neonatal C3H/ST mice infected with 100:1 or 10:1 ratios of WE c54 to WE c2.5 did not develop the syndrome, while animals infected with 1:1 or lower ratios did. Development of GHDS correlated with the extent to which the GH-producing cells of the anterior pituitary were infected. These data indicate that a large excess of disease-negative clones can restrict the replication of disease-positive clones in GH-producing cells, thus preventing the onset of GHDS. In addition, our results indicate that a threshold for phenotypic dominance exists. Interestingly, WE c54 did not entirely outcompete WE c2.5 in mice infected with the 100:1 ratio, suggesting a mechanism whereby pathogenic viruses can be maintained within a nonpathogenic viral population.


Stent and implantable cardioverter defibrillator implantation in medically resistant vasospastic angina patient.
Vasospastic angina, also known as Prinzmetal's angina, is thought to occur due to vascular hyper-reactivity to various stimuli. Response to medical therapy is usually good; however, 1 out of 5 patients has resistant symptoms. Rarely, potentially lethal arrhythmias can occur due to vasospasm, and those patients are reported to have a poorer prognosis. Presently described is a case of resistant vasospastic angina with persistent symptoms under calcium channel blocker and nitrate treatment. The patient presented with hemodynamically unstable rapid-rate ventricular tachycardia, which was quite resistant to recurrent cardioversion. She was treated with stent implantation for definite vasospastic segments of the coronaries, in combination with medical therapy. An implantable cardioverter defibrillator was also implanted for secondary prevention of ventricular arrhythmia, as vasospasm was considered to be a diffuse disease without a certain definitive treatment.


Growth factor biomarkers associated with estrogen- and radiation-induced breast cancer progression.
Breast cancer is the most common cancer in women worldwide. Transformation of a normal cell to a malignant one results from mutations in genes that encode key regulatory proteins. Growth factors are proteins secreted by a variety of transformed cells and tumors and function as autocrine regulators of growth. Biomarkers associated with cancer were examined in human breast epithelial cells transformed by high-LET radiation in the presence of 17beta-estradiol. An established cancer model was used in these studies. The MCF-10F cells that were irradiated with double doses of alpha-particles in the presence of estrogen (60 cGy + E/60 cGy + E, named Alpha 5) showed gradual phenotypic changes relative to control, including tumorigenicity in heterologous animals. Protein expression was determined by quantification of immunofluorescence staining coupled with confocal microscopy. The transforming growth factor alpha, epidermal growth factor, ERK1 and fibroblast growth factor-1 (Int2) protein expression was analyzed. Increased protein expression was observed in non-tumorigenic and tumorigenic alpha-irradiated and estrogen-treated cells. However, Stat-1alpha and pS2 protein expression was only increased in the tumorigenic Alpha 5 and Tumor 2 cell lines. It can be concluded that high-LET radiation in the presence of estrogen-induced changes in the proteins associated with growth factors and their overexpression may be a critical step in the cascade of events that characterize progression in breast cancer.


Relation between UV suppression of polarity in phi X174 and UV sensitivity of rho mutants.
The suppression of polarity by UV irradiation was similar to the suppression by rho mutants. This was demonstrated for a polar nonsense mutant of phage phi X174. Treatment of the host for 30 min with 100 micrograms of the radiomimetic drug mitomycin C per ml was about as effective as 550 J of UV irradiation per m2 in relieving polarity. The shape of the UV survival curves for rho mutants could be linked to a proposed mechanism of UV relief of polarity. Host cell reactivation of phage lambda and W-reactivation of phage G4 were unaffected by rho mutations. UV suppression of polarity is independent of the Hcr- and RecA- phenotypes. An explanation for the UV sensitivity of rho mutants is provided, and several ways are considered in which UV irradiation may deplete cellular rho activity and thereby cause UV relief of polarity. We propose a novel theory that relates the UV inactivation of normal repair-proficient cells to a decrease in rho activity.


The bioavailability and pharmacokinetics of guanfacine after oral and intravenous administration to healthy volunteers.
Guanfacine is a centrally acting alpha-2 adrenergic agonist. The absolute bioavailability, pharmacokinetics, and renal clearance of this antihypertensive drug were investigated in healthy male volunteers. Eighteen subjects received a single oral or intravenous dose of guanfacine 3 mg in a two-way cross-over study design. Blood samples were obtained before dosing and up to 72 hours after dosing for determination of drug levels in plasma. Additional blood samples were obtained for protein binding studies. Urine was collected and pooled for specific intervals up to 96 hours after dosing. The absolute bioavailability of guanfacine after a single oral dose was 81.1%. The elimination half-lives were 13.8 hours and 13.4 hours after oral and intravenous administration, respectively. The volume of distribution results were approximately 6 L/kg by both routes of administration. The mean plasma protein binding results were 71.6%, not influenced by plasma concentration or route of administration. The urinary recovery of guanfacine was 44.3% after oral dosing and 50% after intravenous dosing. Renal clearance of guanfacine was 50% of total body clearance and appeared to be due to a net renal tubular secretory process.


Pigmented monocytes are negative correlates of protection against severe and complicated malaria in Ugandan children.
Pigmented leukocytes are reported to be associated with severe malaria (SM). Blood smears from a case-control study of SM conducted in Apac Hospital in Northern Uganda were examined for pigmented leukocytes to investigate their association with measures of disease and clinical immunity in children less than 5 years old. Pigmented leukocytes, predominated by monocytes, were significantly greater in number in SM by comparison with uncomplicated malaria (UM). SM children with no pigmented leukocytes had significantly elevated hemoglobin, packed cell volumes, and titers of IgG anti-SERA5 by comparison with SM children with pigmented leukocytes. These differences were not observed in UM. A Spearman rank correlation analysis showed, in addition, a negative but weak correlation between pigmented monocytes and titers of IgG anti-Plasmodium falciparum lysate and IgG anti-EBA-175 in both SM and UM children. Thus, numbers of pigmented monocytes might be negative correlates of clinical immunity in a region of holoendemic malaria.


Prospective cohort study of mild cervical spondylotic myelopathy without surgical treatment.
Because the main pathology of cervical spondylotic myelopathy (CSM) is spinal cord damage due to compression, surgical treatment is usually recommended to improve patient symptoms and prevent exacerbation. However, lack of clarity of prognosis in cases that present with insignificant symptoms, particularly those of mild CSM, lead one to question the veracity of this course of action. The purpose of this study was to elucidate the prognosis of mild CSM without surgical intervention by evaluation of clinical symptoms and MR imaging findings. Sixty cases of mild CSM (42 males and 18 females, average age 57.2 years) presenting with scores of 13 or higher on the Japanese Orthopaedic Association (JOA) scale were treated initially by in-bed Good Samaritan cervical traction without surgery. These patients were enrolled between 1995 and 2003 and followed up periodically until the date of myelopathy deterioration or until the end of March 2009. The deterioration of myelopathy was defined as a decline in JOA score to less than 13 with a decrease of at least 2 points. As a prognostic factor, the authors used their classification of spinal cord shapes at their lateral sides on axial T1-weighted MR imaging. "Ovoid deformity" was classified as a situation in which both sides were round and convex, and "angular-edged deformity" where one or both sides exhibited an acute-angled lateral corner. The duration of follow-up was assessed as the tolerance rate of mild CSM using Kaplan-Meier survival analysis and compared between 2 groups classified by MR imaging findings. Furthermore, differences between groups were analyzed by various applications of the log-rank test. Of the initial 60 cases, follow-up records existed for 55, giving a follow-up rate of 91.7% (38 males and 17 females, average age 56.1 years). The mean JOA score at end point was 14.1, which was not statistically different from the mean of 14.5 at the initial visit. Deterioration in myelopathy was observed in 14 (25.5%) of 55 cases, whereas 41 (74.5%) of 55 cases maintained mild extent myelopathy without deterioration through the follow-up period (mean 94.3 months). The total tolerance rate of mild CSM was 70%. However, there was a significant difference in the tolerance rate between the cases with angular-edged deformity (58%) and cases with ovoid deformity (95%; p = 0.049). The tolerance rate of mild CSM was 70% in this study, which proved that the prognosis of mild CSM without surgical treatment was relatively good. However, the tolerance rate of the cases with angular-edged deformity was 58%. Therefore, surgical treatment should be considered when mild CSM cases show angular-edged deformity on axial MR imaging, even if patients lack significant symptoms.


The ultrastructural localization of Echinococcus granulosus antigen 5.
Murine monoclonal and polyclonal antisera, raised against the 38 kDa subunit of Echinococcus granulosus antigen 5, were used to investigate the tissue distribution of the antigen in hydatid cysts. Immunoreactivity was visualized by indirect immunofluorescence on whole protoscoleces, and ultrastructural immunocytochemistry utilizing colloidal gold-based labelling procedures on unsectioned and cryosectioned brood capsules and protoscoleces. In protoscoleces, the 38 kDa subunit of antigen 5 was localized at the interface of parenchymal cells and associated extracellular matrices, as well as along the interface of the tegumentary syncytium in the somal region and its basal matrix. Cytoplasmic labelling of parenchymal cells was rare; when observed, it was associated with vesicles and membranes in cytoplasmic extensions of parenchymal cells. In brood capsules, the antigen was associated with the external face of the plasma of degenerating parenchymal cells. The 38 kDa subunit occurs along the extracellular face of cell membranes, suggesting that antigen 5 is either a component of the membranes or associated extracellular matrices.


[Effects of surgical repair of first degree varicocele on gonadal function and testicular atrophy].
Varicocele is one of the main causes of male infertility. This pathology, in fact, is responsible for progressive anatomical and functional testicular damage. Constant monitoring of subjects suffering from varicocele is therefore necessary. In the present study, we evaluated the effect of varicocele surgical treatment on seminal parameters, testicular growth and pregnancy rate in patients with grade I varicocele. We operated on 47 patients with left grade I varicocele associated with sperm abnormalities and with testicular hypotrophy. A high ligation of the internal spermatic vein and all its collaterals was performed in all patients. The postoperative follow-up showed a significant improvement in seminal parameters (motility, morphology and sperm count) and in testicular volumes. Moreover, a pregnancy rate of 58% was observed. These results confirm the observations of other investigators and suggest that surgical therapy of varicocele is capable of improving seminal parameters, of reversing varicocele-related testicular hypotrophy and of achieving high pregnancy rates even in patients with grade I varicocele.


The Role of Frailty in Failure to Rescue After Cardiovascular Surgery.
Failure to rescue (FTR) is gaining popularity as a quality metric. The relationship between patient frailty and FTR after cardiovascular surgery has not been fully explored. This study aimed to utilize a national database to examine the impact of patient frailty on FTR. Of 5,199,534 patients undergoing cardiovascular surgery between 2000 and 2014, 75,851 (1.5%) were identified from the Nationwide Inpatient Sample database as frail based on the Johns Hopkins Adjusted Clinical Groups frailty-defining diagnoses indicator. Propensity-score matching was used to adjust for patient- and hospital-level characteristics and comorbidities when comparing frail and nonfrail patients. Frail patients were on average older (68 ± 12 years vs 65 ± 12 years; P < .001) and had more comorbidities including heart failure, and chronic lung, liver, or renal disease. Among 68,472 matched pairs, frail patients had significantly higher rates of FTR (13.4% vs 11.9%; P < .001). This contributed to a $39,796 increase in cost per hospitalization (P < .001). Renal failure, respiratory failure, pneumonia, and sepsis were most commonly associated with FTR in frail patients. When hospitals were stratified by risk-adjusted mortality, low-mortality (1st quintile) centers had significantly lower FTR rates and costs among frail patients when compared to high-mortality (5th quintile) centers. Frailty contributes significantly to FTR after cardiovascular surgery. Frail patients can expect better outcomes with lower costs at cardiac surgical centers of excellence that can adequately manage postoperative outcomes. Preoperative assessment of frailty may better guide risk estimation and identification of patients who would benefit from appropriate prehabilitative interventions to optimize outcomes.


Genomic Characterization of a Proteus sp. Strain of Animal Origin Co-Carrying blaNDM-1 and lnu(G).
The emergence of carbapenem-resistant Proteus represents a serious threat to global public health due to limited antibiotic treatment options. Here, we characterize a Proteus isolate NMG38-2 of swine origin that exhibits extensive drug resistance, including carbapenems. Whole-genome sequencing based on Illumina and MinION platforms showed that NMG38-2 contains 24 acquired antibiotic resistance genes and three plasmids, among which, pNDM_NMG38-2, a pPvSC3-like plasmid, is transferable and co-carries blaNDM-1 and lnu(G). Sequence analysis of pPvSC3-like plasmids showed that they share a conserved backbone but have a diverse accessory module with complex chimera structures bearing abundant resistance genes, which are facilitated by transposons and/or homologous recombination. The acquisition of blaNDM-1 in pNDM_NMG38-2 was due to the ISCR1-mediated integration event. Comprehensive analysis of the lnu(G)-bearing cassettes carried by bacterial plasmids or chromosomes revealed a diversification of its genetic contexts, with Tn6260 and ISPst2 elements being the leading contributors to the dissemination of lnu(G) in Enterococcus and Enterobacteriaceae, respectively. In conclusion, this study provides a better understanding of the genetic features of pPvSC3-like plasmids, which represent a novel plasmid group as a vehicle mediating the dissemination of blaNDM-1 among bacteria species. Moreover, our results highlight the central roles of Tn6260 and ISPst2 in the spread of lnu(G).


Lévy laws in free probability.
This article and its sequel outline recent developments in the theory of infinite divisibility and Lévy processes in free probability, a subject area belonging to noncommutative (or quantum) probability. The present paper discusses the classes of infinitely divisible probability measures in classical and free probability, respectively, via a study of the Bercovici-Pata bijection between these classes.


Detection of gastric Helicobacter species in free-ranging lynx (Lynx lynx) and red foxes (Vulpes vulpes) in Sweden.
Specimens of gastric mucosa and liver of 25 free-ranging Eurasian lynx (Lynx lynx), and four red foxes (Vulpes vulpes) shot in Sweden during 1999-2000, were investigated for the presence of Helicobacter species. Histopathology, bacteriologic culture and urease test, Helicobacter genus-specific 16S rDNA PCR analysis, and DNA sequence analysis were applied. Numerous Helicobacter-like organisms were observed histologically in the gastric mucosa of one fox. Helicobacter spp. were detected in the stomach by PCR analysis in 17 (68%) of the lynx and in three (75%) of the foxes. Seven of the positive lynx were also positive in the urease test. PCR fragments, amplified from lynx and foxes, were sequenced and compared with those of known Helicobacter species. PCR products from lynx were closely related (>or=98% homology) to H. heilmannii, and PCR fragments from foxes demonstrated close homology to H. heilmannii and H. salomonis. No Helicobacter spp. or Helicobacter-like organisms could be cultured. The PCR analysis of the liver was negative for all animals. The pathologic significance of the presence of Helicobacter spp. in the stomach of free-ranging lynx and foxes remains uncertain.


Administration of a potent antagonist of protease-activated receptor-1 (PAR-1) attenuates vascular restenosis following balloon angioplasty in rats.
Human platelets possess two distinct thrombin-activated receptors, PAR-1 (protease-activated receptor-1) and PAR-4, whereas human vascular smooth muscle cells possess only PAR-1. Although such thrombin receptors have been studied extensively in vitro, their physiological roles are still rather ill-defined. We have now employed a potent, selective PAR-1 antagonist, RWJ-58259, to probe the in vivo significance of PAR-1 in thrombosis and vascular injury. RWJ-58259 was examined in two thrombosis models in guinea pigs: the arteriovenous (A-V) shunt assay (monitoring thrombus weight) and the Rose Bengal intravascular photoactivation assay (monitoring time to occlusion). Administration of RWJ-58259 (10 mg/kg, total i.v. dose) did not inhibit thrombus formation in either thrombosis model, although local, intrashunt delivery in the A-V shunt model did elicit a modest antithrombotic effect (thrombus weight reduction from 35 +/- 2 to 24 +/- 4 mg). These results are consistent with the presence of more than one thrombin-sensitive receptor on guinea pig platelets, in analogy with human platelets. Indeed, we were able to establish that guinea pig platelets express three thrombin receptors, PAR-1, PAR-3, and PAR-4. We also examined RWJ-58259 in a vascular restenosis model involving balloon angioplasty in rats. Perivascular administration of RWJ-58259 (10 mg) significantly reduced neointimal thickness (77 +/- 5 microm to 45 +/- 5 microm, P < 0.05), clearly demonstrating an important role for PAR-1 in vascular injury. From these results, it is evident that a PAR-1 antagonist is not especially effective for treating platelet-dependent thrombosis; however, it could well be beneficial for treating restenosis attendant to arterial injury.


Do claims-based continuity of care measures reflect the patient perspective?
Continuity of care (CoC) is a cornerstone of the patient-centered medical home (PCMH) and one of the primary means for achieving health care quality. Despite decades of study, however, CoC remains difficult to define and quantify. To incorporate patient experiences into health reform evaluations, it is critical to determine if and how well CoC measures traditionally derived from administrative claims capture patient experiences. In this study, we used claims data and self-reported continuity experiences of 2,620 Medicare beneficiaries who completed the National Health and Health Services Use Questionnaire to compare 16 claims-based CoC indices to a multidimensional patient-reported CoC measure. Our results show that most claims-based CoC measures do not reflect older adults' perceptions of continuous patient-provider relationships, indicating that claims-based assessments should be used in tandem with patient reports for defining, quantifying, and evaluating CoC in health care delivery models.


Spindle cell oncocytoma of the pituitary and pituicytoma: Two tumors mimicking pituitary adenoma.
Spindle cell oncocytoma (SCO) and pituicytoma are rare nonfunctioning tumors of the pituitary. Both tumors are low grade and macroscopically indistinguishable from a nonfunctioning pituitary adenoma.We report one case of SCO and one case of pituicytoma and review the previous literature. One patient was a 39-year-old man who presented with progressive headache, visual blurring, and polyuria of 3-year duration. He underwent partial resection (30% of the tumor) and postoperative adjuvant radiation therapy. Histopathology revealed SCO. However, after 9 months, the residual tumor grew and partial resection (70% of the tumor) was performed again. Four months after the second surgery, the tumor recurred again and he underwent transsphenoidal resection of the tumor with stable residual tumor to date. The other patient was a 59-year-old man who presented with a 3-month history of visual decline, fatigue, difficulty in writing, and polyuria. He underwent transsphenoidal resection (total) of the tumor. Histopathology revealed pituicytoma. He has been stable without evidence of recurrence for 1 year and 4 months. To date, there are 15 reported cases of SCO and 45 reported cases of pituicytoma including our cases. An incomplete resection of the tumor was a significant risk factor for recurrence in both SCO and pituicytoma (P = 0.0014 and P = 0.019, respectively). These tumors have a tendency to be hypervascular, which may hamper total resection. Epithelial membrane antigen (EMA) and mitochondria positivity is characteristic to SCO and they are considered to be important immunomarkers to distinguish these tumors.


Encoding odorant identity by spiking packets of rate-invariant neurons in awake mice.
How do neural networks encode sensory information? Following sensory stimulation, neural coding is commonly assumed to be based on neurons changing their firing rate. In contrast, both theoretical works and experiments in several sensory systems showed that neurons could encode information as coordinated cell assemblies by adjusting their spike timing and without changing their firing rate. Nevertheless, in the olfactory system, there is little experimental evidence supporting such model. To study these issues, we implanted tetrodes in the olfactory bulb of awake mice to record the odorant-evoked activity of mitral/tufted (M/T) cells. We showed that following odorant presentation, most M/T neurons do not significantly change their firing rate over a breathing cycle but rather respond to odorant stimulation by redistributing their firing activity within respiratory cycles. In addition, we showed that sensory information can be encoded by cell assemblies composed of such neurons, thus supporting the idea that coordinated populations of globally rate-invariant neurons could be efficiently used to convey information about the odorant identity. We showed that different coding schemes can convey high amount of odorant information for specific read-out time window. Finally we showed that the optimal readout time window corresponds to the duration of gamma oscillations cycles. We propose that odorant can be encoded by population of cells that exhibit fine temporal tuning of spiking activity while displaying weak or no firing rate change. These cell assemblies may transfer sensory information in spiking packets sequence using the gamma oscillations as a clock. This would allow the system to reach a tradeoff between rapid and accurate odorant discrimination.


Staffing requirements for infection control programs in US health care facilities: Delphi project.
The guideline for staffing infection control programs of 1 infection control professional (ICP) for every 250 occupied acute care beds has been used in many health care facilities in the United States since 1985. Since that time, the health care system, patient populations, and expectations about the work of infection prevention and control programs have changed substantially. The Delphi method was used; data were obtained from a group of ICPs through a series of 10 surveys. Through this iterative process, participant responses were progressively synthesized and areas of agreement and disagreement identified. These surveys were conducted by electronic and paper mail to identify the personal ICP characteristics and structural variables associated with performance of activities required for contemporary infection prevention and control programs in a variety of health care settings. Delphi panel members (n = 32) from 20 states and who represented acute care, long-term care, and community care settings reported tasks in addition to those identified in earlier task analyses as well as expanded responsibilities. Competing responsibilities and lack of adequate resources were the most frequently cited reasons for nonperformance of essential infection control tasks. A ratio of 0.8 to 1.0 ICP for every 100 occupied acute care beds was suggested as adequate staffing by the Delphi panel. Infection control responsibilities have expanded beyond the traditional acute care setting. Recommendations for staffing must not only consider the number of occupied beds (average daily census) but also include the scope of the program, the complexity of the health care facility or system, the characteristics of the patient population, and the unique or urgent needs of the facility and community.


A guideline for the inpatient care of children with pyelonephritis.
Febrile urinary tract infections and pyelonephritis are common in children and frequently lead to hospitalization for management, especially in the child who appears toxic. The American Academy of Pediatrics (AAP) practice parameter on the diagnosis, treatment and evaluation of the initial urinary tract infection in febrile infants and young children provides experience and evidence-based guidelines for the practitioner caring for children between the ages of 2 months to 2 years. No established guideline exists for older children and the AAP guideline does not specifically focus on inpatient care. We conducted a comprehensive review of recently published literature and practice guidelines to develop a consensus on the inpatient diagnosis and management of children with pyelonephritis. Eight recommendations are proposed for the diagnosis and management, including revised guidelines for the imaging studies postpyelonephritis on the basis of current best evidence. Proper diagnosis of pyelonephritis, timely initiation of appropriate therapy and identification of children at risk for renal injury will help to reduce immediate as well as long-term complications due to chronic kidney disease.


[The effect of the dosage of TiO2 and its surface-loaded silver on the photocatalytic degradation of aroclor1260].
The dosage of TiO2 and its surface-loaded silver had notable effect on the photocatalytic degradation of Aroclor1260, under ultraviolet light. The dosage of TiO2 had no proportion to the degradation rate of Aroclor1260, but had an optimal value, which was 3 g/L under the experimental condition. The degradation rate of Aroclor1260 increased with the increasing of loading silver, and the PCBs congeners with higher concentration had higher degradation rate. The catalytic activity of TiO2 increased with the amount of loading silver increasing.


Modification of Glyceraldehyde-3-Phosphate Dehydrogenase with Nitric Oxide: Role in Signal Transduction and Development of Apoptosis.
This review focuses on the consequences of GAPDH S-nitrosylation at the catalytic cysteine residue. The widespread hypothesis according to which S-nitrosylation causes a change in GAPDH structure and its subsequent binding to the Siah1 protein is considered in detail. It is assumed that the GAPDH complex with Siah1 is transported to the nucleus by carrier proteins, interacts with nuclear proteins, and induces apoptosis. However, there are several conflicting and unproven elements in this hypothesis. In particular, there is no direct confirmation of the interaction between the tetrameric GAPDH and Siah1 caused by S-nitrosylation of GAPDH. The question remains as to whether the translocation of GAPDH into the nucleus is caused by S-nitrosylation or by some other modification of the catalytic cysteine residue. The hypothesis of the induction of apoptosis by oxidation of GAPDH is considered. This oxidation leads to a release of the coenzyme NAD+ from the active center of GAPDH, followed by the dissociation of the tetramer into subunits, which move to the nucleus due to passive transport and induce apoptosis. In conclusion, the main tasks are summarized, the solutions to which will make it possible to more definitively establish the role of nitric oxide in the induction of apoptosis.


COVID-19 pandemic and days of absence from work in workers with flu-like symptoms in the City of Rome, Italy.
COVID-19 has dramatically affected working forces. We aim to report our occupational medicine service's experience in managing suspected COVID-19 cases during the pandemic through a retrospec-tive observational study. We compared the number of days employees were absent from work due to flu-like symptoms from March 2020 to February 2021 to the same period the previous year (2019-2020). Two hundred thirty-four patients (+47.2% compared to the previous year) who tested negative for SARS-CoV-2 reported flu-like symp-toms; the number of days of absence from work was 2812 (+190.2% compared to the previous year). On average, employees with flu-like symptoms lost 12.07 working days compared to 6.12 in the previous year (p<0.0001). In conclusion, in our sample COVID-19 has increased the number of working day loss. However, our approach proved to be important, especially during the first months of the pandemic, to limit SARS-CoV-2 spread in workplaces.


Eyes in Staurozoa (Cnidaria): a review.
The presence of dark pigment spots associated with primary tentacles (or structures derived from them, i.e., rhopalioids) in Staurozoa was recently overlooked in a study on the evolution of cnidarian eyes (defined as a "region made of photoreceptor cells adjacent to pigment cells", irrespective of image formation, i.e., including all photoreceptive organs). Review of old and recent literature on Staurozoa shows that dark pigment spots are present in virtually all species of Manania, as well as some species of Haliclystus, Stylocoronella, and probably Calvadosia. The known ultrastructure of ocelli seems to be compatible with light perception, but no immediate response to changes in light intensity have been observed in the behavior of staurozoans. Therefore, although further studies addressing photic behavior are required, we discuss an earlier hypothesis that the dark spots in some stauromedusae may be related to synchronous spawning, as well as the possible sensorial function of rhopalioids. Observations summarized here suggest a possible ninth independent origin of eyes in Cnidaria, within a lineage of benthic medusae. Alternatively, documented similarity across medusae of Cubozoa, Scyphozoa, and Staurozoa-with eyes being topologically associated with primary tentacles in each of these taxa-could indicate shared ancestry and a single origin of eyes in this clade known as Acraspeda. Information on Staurozoa, one of the least studied groups within Cnidaria, is often neglected in the literature, but correctly recognizing the characters of this class is crucial for understanding cnidarian evolution.


Use of cotton-tipped applicators during skin examination and dermatologic surgery.
The cotton-tipped applicator is a widely available and versatile tool for the dermatologist. In addition to the common uses of this inexpensive tool there are many other ways for the dermatologist to use cotton-tipped applicators. From its usefulness in dermatologic examination and potassium hydroxide preparations to its multiple surgical applications, the cotton-tipped applicator is a valuable and underrated tool.


Nematodes of the intestine and swimbladder of the European eel Anguilla anguilla (L.) ascending Pomeranian rivers.
The study focused on the eel (length and weight averaging 23.1 cm and 13.7 g, respectively) ascending Pomeranian rivers in summers of 1999 - 2003. The swim bladder was examined in 322 individuals, the intestine being examined in 272 fish. Anguillicola crassus was present in the swim bladder of 184 fish. Infection prevalence varied between the rivers, the highest prevalence being recorded in the eel caught in the Radew (65.6%) and the lowest in the Wieprza (41.7%). The intensity of infection was generally low, the mean values varying from 2.1 in the Rega to 1.3 in the Wieprza. The coefficient of infection was low (0.11 to 0.12). Spinitectus inermis was present, with low intensity, in the intestine of 18 fish (6.6%). The nematode had not been recorded in the eel in Poland for 70 years. In addition, the intestine of the eel under study was found to house Raphidascaris acus and Paraquimperia tennerima, each present as a single larva. This is the first record of the latter in Poland. The infection of eel from the Radew river that stayed in the fresh water for a longer time was higher than that of the eel found in the Rega and Wieprza.


Thromboelastographic analysis of coagulation and fibrinolysis in rats with nephrotic syndrome induced by daunomycin.
Thromboelastography was carried out to examine the coagulation and fibrinolytic systems in experimental nephrotic rats following treatment with daunomycin. The daunomycin rats showed augmentation of ma on thromboelastography. The response to the plasminogen activator, urokinase, on thromboelastography differed between the daunomycin and control rats. Most daunomycin rats failed to reveal any fibrinolytic effect of urokinase on thromboelastography. Experimental nephrotic rats induced by daunomycin may thus possibly develop hypercoagulability and exhibit a depressed fibrinolytic activity.


Ecological adaptation drives wood frog population divergence in life history traits.
Phenotypic variation among populations is thought to be generated from spatial heterogeneity in environments that exert selection pressures that overcome the effects of gene flow and genetic drift. Here, we tested for evidence of isolation by distance or by ecology (i.e., ecological adaptation) to generate variation in early life history traits and phenotypic plasticity among 13 wood frog populations spanning 1200 km and 7° latitude. We conducted a common garden experiment and related trait variation to an ecological gradient derived from an ecological niche model (ENM) validated to account for population density variation. Shorter larval periods, smaller body weight, and relative leg lengths were exhibited by populations with colder mean annual temperatures, greater precipitation, and less seasonality in precipitation and higher population density (high-suitability ENM values). After accounting for neutral genetic variation, the QST-FST analysis supported ecological selection as the key process generating population divergence. Further, the relationship between ecology and traits was dependent upon larval density. Specifically, high-suitability/high-density populations in the northern part of the range were better at coping with greater conspecific competition, evidenced by greater postmetamorphic survival and no difference in body weight when reared under stressful conditions of high larval density. Our results support that both climate and competition selection pressures drive clinal variation in larval and metamorphic traits in this species. Range-wide studies like this one are essential for accurate predictions of population's responses to ongoing ecological change.


Targeted alpha therapy with 213Bi.
The potential of targeted therapy with the alpha emitter 213Bi has been successfully demonstrated in a large number of preclinical studies and several clinical trials have provided evidence for its feasibility, safety and therapeutic efficacy. This review describes methods for the production of 225Ac and 225Ac/213Bi radionuclide generators, gives an overview of selected preclinical studies and summarizes the current clinical experience with 213Bi.


Simultaneous Nail and Skin Clearance in Ixekizumab Head-to-Head Trials for Moderate-to-Severe Psoriasis and Psoriatic Arthritis.
The lifetime incidence of nail psoriasis in patients with psoriasis is 80-90%, with 23-27% of patients having nail psoriasis at any given time. Nail psoriasis is even more prevalent in patients with comorbid psoriatic arthritis. Complete psoriasis clearance, an achievable therapeutic goal, should ideally include the resolution of nail psoriasis. Here, we assessed simultaneous skin and nail clearance in patients with psoriasis across five head-to-head trials comparing ixekizumab with other biologics. Data were assessed in patients with moderate-to-severe psoriasis (with or without psoriatic arthritis) with nail psoriasis at baseline from the IXORA-R, IXORA-S, UNCOVER-2, UNCOVER-3, and SPIRIT-H2H trials. Ixekizumab patients received IXEQ2W to week 12 and IXEQ4W beyond week 12. PASI 100 depicted complete skin clearance, and PGA-F 0 (IXORA-R) or NAPSI 0 (all other trials) depicted complete nail clearance. Treatment comparisons were evaluated using the Cochran-Mantel-Haenszel test. Non-responder imputation was used for missing data. Ixekizumab achieved significantly greater simultaneous skin and nail complete clearance than etanercept (UNCOVER-2: p < 0.001 and UNCOVER-3: p < 0.001) at week 12, demonstrating an efficacious and rapid response. Across all five head-to-head trials, ixekizumab achieved a high rate of simultaneous skin and nail clearance (range: 28.6-45.9% of patients) by week 24 that was maintained up to week 52 (range: 40.5-51.4% of patients). Ixekizumab achieved numerically greater simultaneous complete clearance than guselkumab at week 24 (p = 0.079), but statistically significant greater simultaneous clearance compared to ustekinumab (p < 0.001) and adalimumab (p = 0.006) at week 24 and week 52 (p < 0.001 and p = 0.007, respectively). In five head-to-head trials, ixekizumab-treated patients had higher rates of simultaneous complete skin and nail clearance compared to etanercept, guselkumab, ustekinumab, and adalimumab, thereby reinforcing ixekizumab's ability to achieve high levels of efficacy in multiple domains of psoriatic disease. NCT01474512, NCT01597245, NCT01646177, NCT03573323, NCT02561806, and NCT03151551.


Evidence for an inhibitory influence of rat placental lactogen on prolactin release in vitro.
Incubation of placental tissue from Day 11 pregnant rats for increasing periods of time resulted in proportionately more rat placental lactogen (rPL) release. The amount of placental tissue incubated correlated directly with the amount of rPL released into the medium. When placentas were coincubated with anterior pituitaries from ovariectomized rats, prolactin release was significantly inhibited. When media from incubations which had contained varying numbers of Day 11 placentas for 24 h were added to vials containing anterior pituitaries, prolactin release was inhibited, proportionate to the amount of rPL in the media. Media from incubations of Day 9 placentas, which contained very little rPL, had no effect on prolactin release. When medium containing anterior pituitary tissue was incubated for 24 h, pituitaries removed, and the medium incubated with placental tissue for an additional 24 h, there was no difference in prolactin levels compared to incubation medium not containing placental tissue. Addition of a trypsin inhibitor to the medium containing placental tissue did not augment the amount of prolactin remaining after a 24-h incubation. Thus it would appear that the placenta does not release a substance into the medium that destroys prolactin. This suggests that secretions from the placenta, presumably rPL, can exert a negative feedback on prolactin secretion at the level of the anterior pituitary.


The pen can heal.
The creative arts, and in particular writing, can be very powerful as a healing therapy. This paper provides an insight into the possibility of using writing as a healing force. It follows my journey through discovery, diagnosis and experiences of neuromyopathy; yet it is a journey travelled by any person faced with a major debilitating condition, be it caused by disease or injury. It gives an insight into the needs and expectations of people who are suffering, and so promotes understanding between people with disabilities and their families, friends and health-care professionals. The added dimension of spirituality gives depth and strength to this healing force.


Tandem RNA isolation reveals functional rearrangement of RNA-binding proteins on CDKN1B/p27Kip1 3'UTRs in cisplatin treated cells.
Post-transcriptional control of gene expression is mediated via RNA-binding proteins (RBPs) that interact with mRNAs in a combinatorial fashion. While recent global RNA interactome capture experiments expanded the repertoire of cellular RBPs quiet dramatically, little is known about the assembly of RBPs on particular mRNAs; and how these associations change and control the fate of the mRNA in drug-treatment conditions. Here we introduce a novel biochemical approach, termed tobramycin-based tandem RNA isolation procedure (tobTRIP), to quantify proteins associated with the 3'UTRs of cyclin-dependent kinase inhibitor 1B (CDKN1B/p27Kip1) mRNAs in vivo. P27Kip1 plays an important role in mediating a cell's response to cisplatin (CP), a widely used chemotherapeutic cancer drug that induces DNA damage and cell cycle arrest. We found that p27Kip1 mRNA is stabilized upon CP treatment of HEK293 cells through elements in its 3'UTR. Applying tobTRIP, we further compared the associated proteins in CP and non-treated cells, and identified more than 50 interacting RBPs, many functionally related and evoking a coordinated response. Knock-downs of several of the identified RBPs in HEK293 cells confirmed their involvement in CP-induced p27 mRNA regulation; while knock-down of the KH-type splicing regulatory protein (KHSRP) further enhanced the sensitivity of MCF7 adenocarcinoma cancer cells to CP treatment. Our results highlight the benefit of specific in vivo mRNA-protein interactome capture to reveal post-transcriptional regulatory networks implicated in cellular drug response and adaptation.


Surface-catalyzed C-C covalent coupling strategies toward the synthesis of low-dimensional carbon-based nanostructures.
Carbon-based nanostructures have attracted tremendous interest because of their versatile and tunable properties, which depend on the bonding type of the constituting carbon atoms. Graphene, as the most prominent representative of the π-conjugated carbon-based materials, consists entirely of sp(2)-hybridized carbon atoms and exhibits a zero band gap. Recently, countless efforts were made to open and tune the band gap of graphene for its applications in semiconductor devices. One promising method is periodic perforation, resulting in a graphene nanomesh (GNM), which opens the band gap while maintaining the exceptional transport properties. However, the typically employed lithographic approach for graphene perforation is difficult to control at the atomic level. The complementary bottom-up method using surface-assisted carbon-carbon (C-C) covalent coupling between organic molecules has opened up new possibilities for atomically precise fabrication of conjugated nanostructures like GNM and graphene nanoribbons (GNR), although with limited maturity. A general drawback of the bottom-up approach is that the desired structure usually does not represent the global thermodynamic minimum. It is therefore impossible to improve the long-range order by postannealing, because once the C-C bond formation becomes reversible, graphene as the thermodynamically most stable structure will be formed. This means that only carefully chosen precursors and reaction conditions can lead to the desired (non-graphene) material. One of the most popular and frequently used organic reactions for on-surface C-C coupling is the Ullmann reaction of aromatic halides. While experimentally simple to perform, the irreversibility of the C-C bond formation makes it a challenge to obtain long-range ordered nanostructures. With no postreaction structural improvement possible, the assembly process must be optimized to result in defect-free nanostructures during the initial reaction, requiring complete reaction of the precursors in the right positions. Incomplete connections typically result when mobile precursor monomers are blocked from reaching unsaturated reaction sites of the preformed nanostructures. For example, monomers may not be able to reach a randomly formed internal cavity of a two-dimensional (2D) nanostructure island due to steric hindrance in 2D confinement, leaving reaction sites in the internal cavity unsaturated. Wrong connections between precursor monomers, here defined as intermolecular C-C bonds forcing the monomer into a nonideal position within the structure, are usually irreversible and can induce further structural defects. The relative conformational flexibility of the monomer backbones permits connections between deformed monomers when they encounter strong steric hindrance. This, however, usually leads to heterogeneous structural motifs in the formed nanostructures. This Account reviews some of the latest developments regarding on-surface C-C coupling strategies toward the synthesis of carbon-based nanostructures by addressing the above-mentioned issues. The strategies include Ullmann coupling and other, "cleaner" alternative C-C coupling reactions like Glaser coupling, cyclo-dehydrogenation, and dehydrogenative coupling. The choice of substrate materials and precursor designs is crucial for optimizing substrate reactivity and precursor diffusion rates, and to reduce events of wrong linkage. Hierarchical polymerization is employed to steer the coupling route, which effectively improves the completeness of the reaction. Effects of byproducts on nanostructure formation is comprehended with both experimental and theoretical studies.


Plasma diafiltration therapy in patients with postoperative liver failure.
Plasma diafiltration (PDF) is a blood purification therapy in which simple plasma exchange (PE) is performed using a selective membrane plasma separator while the dialysate flows outside of the hollow fibers. A prospective, multicenter study was undertaken to evaluate the changes in biochemical examination of blood and the 28-day and 90-day survival rates of patients with postoperative liver failure (PLF). Eleven patients with PLF were studied with the therapy performed 98 times. The Model for End-Stage Liver Disease (MELD) score was categorized into three grades: 20-29, 30-39, and 40 or higher. The survival rate was assessed by the severity of MELD score. The 28-day survival rate was 45.5% and that at 90 days was 27.3%. The levels of total bilirubin, BUN, and creatinine decreased significantly after treatment. On the other hand, the levels of total protein increased after treatment and those of albumin did not change significantly. PDF may be the useful blood purification therapies for use in cases of PLF in terms of medical economics and the removal of water-soluble and albumin-bound toxins.


Assessment and management of hospitalized suicidal patients.
Suicide in inpatient psychiatric settings is a critical problem. A comprehensive literature review was performed to determine risk factors for inpatient suicide, instruments for assessing suicide, and treatment of hospitalized suicidal patients. Findings suggested that root causes of inpatient suicide were factors related to the treatment environment, failure to assess patient behavioral characteristics, and staff reliance on no-suicide contracts. Recommendations include assessing suicide risk regularly throughout hospitalization, including on admission, during changes in a patient's mental or physical status, after a change in observation level, and before discharge. Orientation and inservice education for all staff and additional research on the psychometric properties of available suicide assessment instruments are also essential.


Omental roll-up: a technique for islet engraftment in a large animal model.
Attrition of transplanted islets is significant after hepatic embolization. This study was designed to investigate a novel surgical technique for islet transplantation into the omentum. This site allows placement of the islets in a three-dimensional (3D) matrix, with growth factors, to temporarily culture the islets in vivo while revascularization progresses. Five female dogs (three partial and two total pancreatectomies) received an autologous islet transplant in the omentum. Islets were suspended in 1 mL of PBS containing 10 ug of vascular endothelial growth factor (VEGF). Fresh autologous plasma (10 mL) was mixed with the islet/VEGF suspension. The coagulum containing the islets and VEGF was then placed on the greater omentum. The leading edge of omentum was rolled up to secure the islet/VEGF/coagulum in position and to present the thin islet layer with two omental surfaces for implantation. Omentum was recovered at 2, 13, 21, 42, and 180 d. Immunohistochemical staining for synaptophysin, glucagon, and insulin confirmed the presence of transplanted islets in all omenta. Insulin and C peptide production from the omental islets was confirmed in portal venous samples, and normalization of morning glucose levels beginning on day 7 was seen in the total pancreatectomy experiment. Autologous islets implant in rolled-up omentum when placed as a VEGF/autologous plasma coagulum. This technique has potential benefits, including the opportunity to accelerate revascularization and to investigate local strategies for modulating the immune response.


Effect of a synesthete's photisms on name recall.
A multilingual, colored-letter synesthete professor (MLS), 9 nonsynesthete multilingual professors and 4 nonsynesthete art professors learned 30 names of individuals (first and last name pairs) in three trials. They recalled the names after each trial and six months later, as well as performed cued recall trials initially and after six months. As hypothesized, MLS recalled significantly more names than control groups on all free recall tests (except after the first trial) and on cued recall tests. In addition, MLS gave qualitatively different reasons for remembering names than any individual control participant. MLS gave mostly color reasons for remembering the names, whereas nonsynesthetes gave reasons based on familiarity or language or art knowledge. Results on standardized memory tests showed that MLS had average performance on non-language visual memory tests (the Benton Visual Retention Test-Revised--BURT-R, and the Rey-Osterrieth Complex Figure Test--CFT), but had superior memory performance on a verbal test consisting of lists of nouns (Rey Auditory-Verbal Learning Test--RAVLT). MLS's synesthesia seems to aid memory for visually or auditorily presented language stimuli (names and nouns), but not for non-language visual stimuli (simple and complex figures).


BRCA1 overexpression sensitizes cancer cells to lovastatin via regulation of cyclin D1-CDK4-p21WAF1/CIP1 pathway: analyses using a breast cancer cell line and tumoral xenograft model.
It is well established that statins display potent anticancer activity in several types of proliferating tumor cells. However, how to promote the sensitivity of statins to mammary cancer is yet to be completely deciphered. The purpose of this study was to investigate whether breast cancer susceptibility gene 1 (BRCA1) overexpression sensitizes mammary cancer cells to statins. MCF-7 cells, which have only one wild-type BRCA1 allele, were transfected with pcDNA3-beta-HA-hsBRCA1 plasmids via liposomes to reconstitute BRCA1 overexpression human breast cancer cell line, and tumoral xenografts with BRCA1 overexpression were subsequently established in BALB/c nude mice. Then, the inhibitory activity of lovastatin on cancer cells and tumoral xenografts, and the underlying mechanism involving in cell-cycle regulatory proteins were analyzed. The proliferative ability of MCF-7 cells treated with lovastatin was reduced compared to normal, and further decreased in the presence of excess BRCA1, detected by methyl thiazolyl tetrazolium and flow cytometry techniques in vitro or by 5-bromodeoxyuridine incorporation in vivo. Additionally, the mRNA and protein expression of cyclin D1, cyclin-dependent kinase 4 (CDK4) and retinoblastoma protein (pRb), was further down-regulated under exposure to lovastatin in condition of BRCA1 overexpression, but the expression of p21WAF1/CIP1, a cyclin-dependent kinase inhibitor (CDKI), was further up-regulated, both in vitro and in vivo detected with quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. Moreover, we found the further reduced volume of tumoral xenografts treated with lovastatin in the presence of BRCA1 overexpression. Our results suggest that BRCA1 overexpression sensitizes cancer cells to lovastatin via regulation of cyclin D1-CDK4-p21WAF1/CIP1 pathway, which will provide an innovative experimental framework to study control of breast cancer cell proliferation.


[Linkage analysis of cytokine and cytokine-related receptor gene loci and essential hypertension in Chinese].
To investigate the genetic linkage between several cytokine and cytokine-related receptor gene loci and essential hypertension (EH) in Chinese. Linkage between seven genetic markers and EH in 95 Chinese nuclear families with EH (including 477 subjects) was analyzed using a technique of fluorescence-based gene scan with DNA short tandem repeat loci. These markers were selected from the chromosomal regions nearby eight cytokines and their receptor genes. The two-point non-parametric linkage analysis (NPL), maximum Lod score and transmission/disequilibrium test (TDT) with GENEHUNTER software package were used in this study. Result of TDT showed significant transmission disequilibrium between D14S61 and EH (Chi square 14.29,P=0.00016) although NPL and Lod score revealed no significant linkage (Z=0.78, P>0.05 and Lod score =0.72 respectively) at this locus. No linkage between other loci typed and EH was found by the three genetic analysis methods (P>0.05 or Lod score<-1). Alleles at D14S61 were of significant transmission disequilibrium in affected siblings. Transforming growth factor beta 3 is 0.1 cM away from D14S61, which suggests that the relationship between genes at or near this regions and EH needs to be further explored.


Biotechnological strategies for phytoremediation of the sulfonated azo dye Direct Red 5B using Blumea malcolmii Hook.
Tissue cultured shrub plants of Blumea malcolmii were found to decolorize Malachite green, Red HE8B, Methyl orange, Reactive Red 2 and Direct Red 5B at 20 mg L(-1) concentration to varying extent within three days. A significant induction in the activities of lignin peroxidase, tyrosinase, DCIP (2,6-dichlorophenol-indophenol) reductase, azoreductase and riboflavin reductase in the roots was observed during the decolorization of Direct Red 5B, which indicated their crucial role in the metabolism of the dye. HPLC (High Performance Liquid Chromatography) and FTIR (Fourier Transform Infrared Spectroscopy) analysis of the samples before and after decolorization of the dye confirmed the phytotransformation of Direct Red 5B. The GC-MS (Gas Chromatography Mass Spectroscopy) analysis of the products led us to the identification of three metabolites formed after phytotransformation of the dye as 4-(4-amino-phenylazo)-benzene sulfonic acid, 3-amino-7-carboxyamino-4-hydroxy-naphthalene-2-sulfonic acid and 7-carboxyamino-naphthalene-2-sulfonic acid.


HIV-care access among people with incarceration experience in St. Petersburg, Russia.
Little is known about the clinical care experiences of HIV-infected persons in St. Petersburg who have experience with incarceration. To address this question, we conducted a capture-recapture study to identify individuals who had been diagnosed with HIV infection while incarcerated and who subsequently presented for medical care in St. Petersburg, Russia following release from prison. We matched 292 HIV-positive prisoners tested by the prison system in 2010 to the medical records at the St. Petersburg AIDS Center in the following 4 years. The data analysis shows that as many as half of HIV+ prisoners fail to seek treatment in the community upon release. Of those who had sought care post-release, only 36% were receiving HAART. Of the 109 individuals for whom tuberculosis testing was indicated post-release, 36.7% were found to be reactive. Despite the limitations of the data, this study is the first of its kind to review records documenting HIV care among prisoners in Russia post-incarceration. In addition to providing important descriptive information about this marginalized population, the findings from this study highlight areas where HIV control efforts could be improved in order to address the HIV epidemic in the Russian Federation.


An enzyme linked immunoassay for estimation of antibodies to Newcastle disease virus strains.
The sensitivity of enzyme linked immunoassay (ELISA) was compared to that of haemagglutination inhibition (HI) test in detection of humoral antibodies in birds vaccinated with Newcastle disease virus (NDV). The highest antibody titre at day 21 post-vaccination as detected by ELISA in the sera of vaccinated birds was 2560 by all strains in contrast to the HI titres of 640 to 1280. The antibody titre was higher in all pre- and post-vaccination sera as determined by ELISA than detected by HI test.


Passive in situ biobarrier for treatment of comingled nitramine explosives and perchlorate in groundwater on an active range.
Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX), and perchlorate (ClO4-) are common, and often co-mingled, contaminants at military ranges worldwide. This project investigated the feasibility of using a passive emulsified oil biobarrier plus a slow release pH buffering reagent to remediate RDX, HMX, and ClO4- in a low pH aquifer at an active range. A 33 m biobarrier was emplaced perpendicular to the contaminant plumes, and dissolved explosives, perchlorate, and other relevant parameters were monitored. The pH increased and the DO and ORP decreased after emulsified oil injection, leading to >90% reductions in perchlorate, RDX, and HMX compared to upgradient groundwater. Some nitroso breakdown products were observed immediately downstream of the barrier, but generally decreased to below detection limits farther downgradient. First-order rate constants of approximately 0.1/d were obtained for all three contaminants. Dissolved metals (including As) also increased in the wells immediately adjacent to the barrier, but attenuated as the plume re-aerated in downgradient areas. Biobarrier installation and sampling were performed during scheduled range downtime and had no impacts to ongoing range activities. The field trial suggests that an emulsified oil biobarrier with pH buffering can be a viable alternative to remove explosives and perchlorate from shallow groundwater on active ranges.


Genetic-Based Optimization of 3D Burch-Schneider Cage With Functionally Graded Lattice Material.
A Burch-Schneider (BS) cage is a reinforcement device used in total hip arthroplasty (THA) revision surgeries to bridge areas of acetabular loss. There have been a variety of BS cages in the market, which are made of solid metal. However, significant differences in structural configuration and mechanical behavior between bone and metal implants cause bone resorption and interface loosening, and hence lead to failure of the implant in the long term. To address this issue, an optimal design framework for a cellular BS cage was investigated in this study by genetic algorithm and topology optimization, inspired by porous human bone with variable holes. In this optimization, a BS cage is constructed with functionally graded lattice material which gradually evolves to achieve better mechanical behavior by natural selection and natural genetics. Clinical constraints that allow adequate bone ingrowth and manufacturing constraint that ensures the realization of the optimized implant are considered simultaneously. A homogenization method is introduced to calculate effective mechanical properties of octet-truss lattice material in a given range of relative density. At last, comparison of the optimum lattice BS cage with a fully solid cage and a lattice cage with identical element density indicates the validity of the optimization design strategy proposed in this article.


LED Illumination for High-Quality High-Yield Crop Growth in Protected Cropping Environments.
Vegetables and herbs play a central role in the human diet due to their low fat and calory content and essential antioxidant, phytochemicals, and fiber. It is well known that the manipulation of light wavelengths illuminating the crops can enhance their growth rate and nutrient contents. To date, it has not been easy to generalize the effects of LED illumination because of the differences in the plant species investigated, the measured traits, the way wavelengths have been manipulated, and the plants' growing environments. In order to address this gap, we undertook a quantitative review of LED manipulation in relation to plant traits, focusing on vegetables and herbs. Here, we use standardized measurements of biomass, antioxidant, and other quantitative characteristics together with the whole range of the photosynthetic photon flux density (PPFD). Overall, our review revealed support for the claims that the red and blue LED illumination is more reliable and efficient than full spectrum illumination and increases the plant's biomass and nutritional value by enhancing the photosynthetic activity, antioxidant properties, phenolic, and flavonoids contents. Although LED illumination provides an efficient way to improve yield and modify plant properties, this study also highlights the broad range of responses among species, varieties traits, and the age of plant material.


[Scoping review of clinical evidence of Chinese patent medicines for digestive system diseases in children].
This study analyzed and reported the basic information and clinical evidence of Chinese patent medicines for digestive system diseases in children in a scoping review manner. Based on the drug instructions, the basic information of Chinese patent medicines for digestive system diseases in children was obtained by searching the three lists of national medicines. At the same time, the relevant clinical literatures from the first day of establishment to March 7, 2022 were obtained from Chinese and English databases. According to the screening criteria, 39 Chinese patent medicines were included, involving 8 dosage forms. Eight Chinese medicines including Crataegi Fructus, Poria, Citri Reticulatae Pericarpium, Hordei Fructus Germinatus, Arecae Semen, Massa Medicata Fermentata, Dioscoreae Rhizoma, and Atractylodis Macrocephalae Rhizoma were frequently used, and the main effects were invigorating spleen, checking diarrhea, promoting digestion, clearing heat, and harmonizing stomach. The indications for Chinese patent medicines were mainly diarrhea, anorexia, food accumulation, dyspepsia, and rotavirus enteritis in children. Among all drug instructions, only 4 mentioned adverse reactions and 6 mentioned contraindications. Ninety-two clinical studies were included ultimately, including 84 randomized controlled studies, 2 systematic reviews/Meta-analysis, 1 retrospective study, and 5 case series. The literatures only covered 21 kinds of Chinese patent medicines, with the most studies related to Xingpi Yanger Granules, accounting for 32.6% of the total literature volume. The sample size in the literatures was mainly focused on 51-200 cases, and 51-100 cases were selected by the most literatures, accounting for 34.45%. The interventions of the experimental group were mainly Chinese patent medicines or Chinese patent medicines combined with western medicines. The literatures with treatment course of 0-7 d accounted for the largest proportion(51.10%). The effective rate and symptom improvement time were used as the indexes to evaluate the results. The main adverse reactions were vomiting, constipation, nausea, rash, cold, diarrhea, redness of the skin around the umbilicus, or red itchy skin. The analysis of this study found that Chinese patent medicines have good curative effect and research prospects in the treatment of digestive system diseases in children. However, most clinical evidence has problems, such as limited indexes to evaluate the results, lack of traditional Chinese medicine characteristics, uneven quantity and low quality of Chinese patent medicine literatures, and insufficient specification of instructions. In the future, high-quality clinical studies on this field should be actively carried out, and economic studies and clinical comprehensive evaluation of Chinese patent medicines should be strengthened to explore the characteristics and advantages of its treatment, so as to provide decision-making basis for finding the accurate clinical positioning and promoting the rational clinical application of Chinese patent medicines for treating digestive system diseases in children.


Negotiating treatment and managing expectations in chronic kidney disease: A qualitative study in Argentina.
To describe how patients with CKD negotiated assigned responsibilities in the management of their disease, resulting in potential relational nonadherence. Qualitative study performed in two healthcare facilities in Buenos Aires, Argentina, including 50 patients and 14 healthcare providers. We conducted semistructured interviews which were analysed using a frame of reference with concepts of Burden of Treatment and Cognitive Authority theories. Adherence to treatment defined "good patients". Patients needed to negotiate starting treatment, its modality and dialysis schedule, although most patients felt they did not participate in the decision process and that providers did not acknowledge implications of these decisions on their routine. Some patients skipped dialysis if concerns were not attended. Regularly, patients negotiated frequency of visits, doses, dietary restrictions and redefined relationships with their support networks, sometimes with devasting effects. As a result of overwhelming uncertainty some patients refused enrolling into a transplant program. When the frequency of complications increased, patients considered abandoning dialysis. When patients perceived demands were excessive or conflicting, they entered into negotiations. Relationally induced nonadherence may arise when professionals do not or cannot enter into negotiations over patients' beliefs or knowledge about what is possible for them to do.


[Influence of metabolic syndrome on activities of daily living in middle-aged and elderly population in China: a prospective cohort study].
Objective: To examine the associations between metabolic syndrome (MS) and the risks for impaired activities of daily living (ADL) in the middle-aged and elderly population in China and provide basis for improving healthy life expectancy. Methods: Prospective cohort study design was used in this study. Based the data of China Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2018 and the baseline data in 2011, the follow up for ADL outcomes was conducted in 2013, 2015 and 2018 respectively, and the participants recruited in 2013 and 2015 were new baseline populations. The participants with impaired ADL in three baseline populations were excluded. Cox proportional hazard model was used to estimate the effect of different components and number of MS components on the risk for ADL impairment in the middle-aged and elderly population in China. Results: In 59 795 person-years of follow-up, a total of 1 011 cases of ADL impairments were recorded. The incidence density of ADL impairment was 16.91 per 1 000 person-year; The findings of Cox regression analysis showed that compared with the middle aged and elderly people without MS, the risk for ADL impairments was 1.29 times higher (95%CI: 1.12-1.50) for those with one component of MS, 1.32 times higher (95%CI:1.07-1.64) for those with hyperlipemia complicated with diabetes, 1.78 times higher (95%CI: 1.22-2.59) for those with obesity and one component of MS, 2.48 times higher (95%CI:1.59-3.85) for those with hypertension complicated with hyperlipemia, 3.51 times higher (95%CI:1.66-7.43) for those with hypertension complicated with diabetes, 1.80 times higher (95%CI: 1.40-2.32) for those with ≥3 MS, respectively. Compared with the middle-aged and elderly population without MS, the risk for impaired ADL increased by 30% (HR=1.30, 95%CI: 1.13-1.51), 54% (HR=1.54, 95%CI: 1.28-1.85) and 87% (HR=1.87, 95%CI:1.45-2.41), respectively, in the middle-aged and elderly with one, two, and more than three components of MS, with a significant dose-response relationship that ADL impaired risks increased as the number of MS components increased (P<0.001). Conclusions: Our findings suggested that MS is a risk factor for ADL impairment in middle-aged and elderly population in China. Prevention and early intervention of obesity, hypertension, hyperlipemia, diabetes and metabolic syndrome could help to reduce or delay the incidence of ADL impairment.


Biomimics of fungal cell-cell recognition by use of lectin-coated nylon fibers.
When the mycoparasitic, biocontrol fungus Trichoderma harzianum was allowed to grow on nylon fibers treated with concanavalin A or Sclerotium rolfsii lectin, it coiled around the nylon fibers and produced hooks in a pattern similar to that observed with the real host hyphae. The incidence of interaction between T. harzianum and S. rolfsii lectin-treated fibers was significantly higher than that of the controls (untreated or blocked activated fibers). These findings provide direct evidence for the role of lectins in mycoparasitism.


Cyclodextrins and Cyclodextrin Derivatives as Green Char Promoters in Flame Retardants Formulations for Polymeric Materials. A Review.
Polymers are intrinsically flammable materials; hence, fire retardance (FR) is required in their most common applications (i.e., electronic and construction, to mention some). Recently, it has been reported that cyclodextrin (CD) and cyclodextrin derivatives are beginning to be introduced into Intumescent Fire Retardant (IFR) formulations in place of pentaerythritol, which is used in IFRs that are currently on the market. Since IFRs are of less environmental concern than their hazardous halogen containing counterparts, the use of natural origin compounds in IFRs provides a way to comply with green chemistry issues. BCD and BCD derivatives presence in IFR mixtures promotes a higher yield of blowing gases and char when polymeric materials undergo combustion. Both processes play important roles in intumescence. The key rule to obtain in insulating compact char is the good dispersion of the nanoparticles in the matrix, which can be achieved by functionalizing nanoparticles with BCD derivatives. Moreover, CD derivatives are attractive because of their nanosized structure and their ability to form inclusion complexes with many compounds used as FR components, reducing their release to the environment during their shelf life of FR items. Often, fire retardance performed by BCD and BCD derivatives accompanies other relevant properties, such as improved mechanical resistance, washability resistance, self healing ability, thermal conductivity, etc. The application of CD fire retardant additives in many polymers, such as poly(lactic acid), poly(propylene), poly(vinyl acetate), poly(methyl methacrylate), linear low density poly(ethylene), polyamides, and polyesters are comprehensively reviewed here.


The role of ultrasound in breast imaging.
This report describes several patients in whom diagnostic ultrasound played a significant role in the detection and diagnosis of breast masses. Diagnostic ultrasound was able to verify whether breast mass was or was not present. Secondly, ultrasound was able to determine whether the mass was definitely benign and no further evaluation was necessary, or whether the mass was possibly malignant and needed a biopsy. The important role diagnostic ultrasound plays in breast imaging and its appropriate clinical applications are discussed.


Core binding factor acute myeloid leukemia: the impact of age, leukocyte count, molecular findings, and minimal residual disease.
Most patients with acute myeloid leukemia (AML) and genetic rearrangements involving the core binding factor (CBF) have favorable prognosis. In contrast, a minority of them still have a high risk of leukemia recurrence. This study investigated the adverse features of CBF AML that could justify investigational therapeutic approaches. One hundred and fifty patients (median age 42 yr, range 16-69) with CBF AML (RUNX1-RUNX1T1 n = 74; CBFB-MYH11 n = 76) were prospectively enrolled into two consecutive CETLAM protocols at 19 Spanish institutions. Main clinic and biologic parameters were analyzed in the whole series. In non-selected cases with available DNA samples, the impact of molecular characterization and minimal residual disease (MRD) was also studied. Overall, complete remission (CR) rate was 89% (94% in ≤50 yr old and 72% in >50 yr, P = 0.002). At 5 yr, cumulative incidence of relapse (CIR) was 26 ± 1%, disease-free survival (DFS) 62 ± 6%, and overall survival (OS) 66 ± 4%. In multivariate analyses, leukocyte count above 20 × 10(9) /L, BAALC over-expression, and high copy numbers of RUNX1-RUNXT1 or CBFB-MYH11 after induction chemotherapy (CT) led to increased relapse rate. Regarding OS, age >50 yr, leukocyte count above 20 × 10(9) /L, and increased MN1 expression were adverse features. Age, leukocyte counts, BAALC, and MN1 gene expressions as well as high copy numbers of RUNX1-RUNXT1 or CBFB-MYH11 after induction chemotherapy are useful tools to predict the outcome and should be considered for risk-adapted therapy.


Neural stem cell temporal patterning and brain tumour growth rely on oxidative phosphorylation.
Translating advances in cancer research to clinical applications requires better insight into the metabolism of normal cells and tumour cells in vivo. Much effort has focused on understanding how glycolysis and oxidative phosphorylation (OxPhos) support proliferation, while their impact on other aspects of development and tumourigenesis remain largely unexplored. We found that inhibition of OxPhos in neural stem cells (NSCs) or tumours in the Drosophila brain not only decreases proliferation, but also affects many different aspects of stem cell behaviour. In NSCs, OxPhos dysfunction leads to a protracted G1/S-phase and results in delayed temporal patterning and reduced neuronal diversity. As a consequence, NSCs fail to undergo terminal differentiation, leading to prolonged neurogenesis into adulthood. Similarly, in brain tumours inhibition of OxPhos slows proliferation and prevents differentiation, resulting in reduced tumour heterogeneity. Thus, in vivo, highly proliferative stem cells and tumour cells require OxPhos for efficient growth and generation of diversity.


Respiratory response to arm elevation in patients with chronic airflow obstruction.
We have shown that patients with chronic airflow obstruction (CAO) complain of disabling dyspnea when performing seemingly trivial tasks with unsupported arms. Surprisingly little is known about the metabolic and ventilatory responses to unsupported upper extremity activity even though some of the muscles of the upper torso and shoulder girdle are used to perform simple and complex everyday tasks as well as partake in ventilation. To determine the effect of simple arm elevation in 20 patients with CAO we studied their lung function, VO2, VCO2, and VE, with arms down at the side (AD), during 2 min with arms extended forward up to shoulder level (AE), and during recovery. To determine the pattern of ventilatory muscle recruitment we also measured endoesophageal (Ppl), gastric (Pg), and transdiaphragmatic (Pdl) pressures. In five of the patients the electromyographic signal (EMG) of the sternocleidomastoid (Sm) muscle was recorded and analyzed in its time domain (amplitude) and power spectrum density (median frequency). Within 30 s of arm elevation VO2, VCO2, and VE rose and remained elevated for 1 min after the arms were lowered. The increase in VE resulted from increases in respiratory rate and minimal rise in tidal volume (VT). With AE, FEV1 decreased by 5% (p less than 0.02) but FRC increased by 2% (p less than 0.05). Peak inspiratory pressure (Pimax) dropped from 54 +/- 4 to 48 +/- 4 cm H2O (p less than 0.005); Pdimax remained unchanged. Immediately after raising the arms Pgi, inspiratory swing in Pdi (delta Pdi), end-expiratory Ppl, and end-expiratory Pg increased significantly.(ABSTRACT TRUNCATED AT 250 WORDS)


[Dengue shock syndrome: decoding the pathophysiology].
Considered as major human arbovirosis, dengue occurs in several clinical forms. Some forms can lead to fatal complications such as dengue shock syndrome. This hypovolemic shock cannot be predicted and specific curative treatments are still lacking, and thus management of patients with dengue is difficult. The purpose of this review is to describe state-of-the-art of the knowledge on the pathophysiology of shock syndrome and to highlight the interest of high-content screening methods in translational approaches between research and medicine for investigation of individual response during dengue shock syndrome.


Multi-omic underpinnings of epigenetic aging and human longevity.
Biological aging is accompanied by increasing morbidity, mortality, and healthcare costs; however, its molecular mechanisms are poorly understood. Here, we use multi-omic methods to integrate genomic, transcriptomic, and metabolomic data and identify biological associations with four measures of epigenetic age acceleration and a human longevity phenotype comprising healthspan, lifespan, and exceptional longevity (multivariate longevity). Using transcriptomic imputation, fine-mapping, and conditional analysis, we identify 22 high confidence associations with epigenetic age acceleration and seven with multivariate longevity. FLOT1, KPNA4, and TMX2 are novel, high confidence genes associated with epigenetic age acceleration. In parallel, cis-instrument Mendelian randomization of the druggable genome associates TPMT and NHLRC1 with epigenetic aging, supporting transcriptomic imputation findings. Metabolomics Mendelian randomization identifies a negative effect of non-high-density lipoprotein cholesterol and associated lipoproteins on multivariate longevity, but not epigenetic age acceleration. Finally, cell-type enrichment analysis implicates immune cells and precursors in epigenetic age acceleration and, more modestly, multivariate longevity. Follow-up Mendelian randomization of immune cell traits suggests lymphocyte subpopulations and lymphocytic surface molecules affect multivariate longevity and epigenetic age acceleration. Our results highlight druggable targets and biological pathways involved in aging and facilitate multi-omic comparisons of epigenetic clocks and human longevity.


Management of critical lower limb ischemia in endovascular era: experience from 511 patients.
This study aims at the assessment of the achievability of the endovascular treatment of patients with critical limb ischemia (CLI) and the role of bypass in such patient. This is a prospective study conducted on patients with chronic atherosclerotic critical lower limb ischemia presenting to us over a period of 3 years. Patients presenting with nonsalvageable limbs requiring primary major amputation and nonatherosclerotic causes of CLI were excluded. Endovascular treatment was the first choice modality of treatment in revascularization of all patients. Open surgery was offered selectively for patient whom endovascular failed or complicated and for long TransAtlantic Inter-Society Consensus (TASC) II lesions in fit patients. This study included 511 cases of CLI, and the mean age was 64.5 years. Patients with Rutherford IV, V, and VI were 19.25, 60.5, and 19.25%, respectively. The TASC II aortoiliac lesions were as follows: A, B, C, and D in 33.7, 12,15.7, and 38.6%, respectively, and infrainguinal lesions were A, B, C, and D in 3.7, 19, 35.4, and 68.3%, respectively. A total of 78.3% of patients were treated by endovascular totally, while 16% were treated by surgery from the start, 3.7% of endovascular cases were converted to open surgery after failure of endovascular treatment, and 2% was offered hybrid treatment. Crossing of lesions by subintimal and intraluminal was 12.5 and 87.5%, respectively. Technical success in endovascular was 94%; however, we could successfully revascularize 96.8% of all CLI presented in this study by either surgery or endovascular. On 24 months follow-up, primary patency, secondary patency, and limb salvage by percutaneous transluminal angioplasty are 77.8, 84.7, and 90.7%, respectively. Revascularization by endovascular achieves high technical success and limb salvage in CLI, hence should be considered as preferred choice of treatment. However, both endovascular and surgery should not be counteracting each other and using both can revascularize 96.6% of CLI.


[Social burden caused by poliomyelitis].
Social burden caused by paralyzed poliomyelitis was analysed, using data from a Sampling Survey of Handicapped People in China, in 1987. The study results showed: 29.94% of 1707 handicapped polio victims aged 6 or over were not able to go to school; 44.23% of them could not take care of their daily life; 36.32% of them could not play out-door and do shopping; 2.58% of them could not normally communicate with others. 84.53% of the 1487 handicapped victims caused by polio aged 15 or over wholly or partly lost their working ability. We also compared handicapped people's employment rate and the status of marriage with non-handicapped people. Data showed that the employment rate and the number of married handicapped polio victims were remarkably lower then those non-handicapped people.


Cellular Effects of Cyclodextrins: Studies on HeLa Cells.
Cyclodextrins are high molecular weight, hydrophilic, cyclic, non-reducing oligosaccharides, applied as excipients for the improvement of the solubility and permeability of insoluble active pharmaceutical ingredients. On the other hand, beta-cyclodextrins are used as cholesterol sequestering agents in life sciences. Recently, we demonstrated the cellular internalization and intracellular effects of cyclodextrins on Caco-2 cells. In this study, we aimed to further investigate the endocytosis of (2-hydroxylpropyl)-beta-(HPBCD) and random methylated-beta-cyclodextrin (RAMEB) to test their cytotoxicity, NF-kappa B pathway induction, autophagy, and lysosome formation on HeLa cells. These derivatives were able to enter the cells; however, major differences were revealed in the inhibition of their endocytosis compared to Caco-2 cells. NF-kappa B p65 translocation was not detected in the cell nuclei after HPBCD or RAMEB pre-treatment and cyclodextrin treatment did not enhance the formation of autophagosomes. These cyclodextrin derivates were partially localized in lysosomes after internalization.


The assumption of equilibrium in the analysis of migration and interregional differences: a review of some recent research.
"This paper questions the plausibility of the assumption of interregional equilibrium in recent research into migration and the valuation of amenities in the United States. It is shown that it is difficult to develop a satisfactory explanation for continuing net migration which is compatible with the equilibrium assumption, and that recent relevant research generally fails to support the idea that the U.S. economy is in equilibrium. The association of higher rent levels with in-migration is explained as a short-run phenomenon. If the spatial economy is in disequilibrium, then the valuations of amenities assuming equilibrium will be biased, being probably too low in areas of net in-migration and too high in areas of net out-migration."


Effect of Potassium Supply on the Rate of Phloem Sap Exudation and the Composition of Phloem Sap of Ricinus communis.
The composition of phloem sap has been investigated in Ricinus communis var. gibsonii, grown for 2 weeks on nutrient solution of low and high potassium content (K(1) and K(2)). Diagonal cuts were made in the bark of the stem resulting in the exudation of clear droplets which mainly consisted of phloem sap. Although the plants at low K (0.4 mm) and high K (1 mm) did not differ in growth, leaf area, height, or stem circumference, the rate of exudation of the high K plants was about twice as high as that of the plants with the lower K supply. This promoting effect of K on exudation did not result in a dilution of organic (sucrose, UDP-glucose, ATP, UTP) and inorganic constituents of the phloem sap. For the following compounds, even significantly higher concentrations in the exudate were observed in the K(2) plants: potassium, raffinose, glucose 6-phosphate, and fructose 6-phosphate. Also, the osmotic pressure of the phloem sap was substantially increased in the higher K treatment. Experiments in which labeled (14)CO(2) was applied to one leaf showed that K had a favorable effect on the assimilation of CO(2), and in particular promoted the export of photosynthates from the leaf. It is suggested that the higher rate of phloem-loading in the plants with the better K supply is due to the higher CO(2) assimilation rate and especially to a better provision of ATP required for phloem loading. Higher phloem-loading rates result in higher osmotic pressure in the sieve tubes which probably gave rise to the higher flow rates observed in the plants with improved K supply.


Bacteriocolonic pathway for ethanol oxidation: characteristics and implications.
Alcohol ingested orally is transported to the colon by blood circulation, and after the distribution phase, intracolonic ethanol levels are equal to those in the blood. Recent studies in our laboratory suggest that in the large bowel ethanol is oxidized by a bacteriocolonic pathway. In this pathway intracolonic ethanol is at first oxidized by bacterial alcohol dehydrogenase to acetaldehyde. Then acetaldehyde is oxidized either by colonic mucosal or bacterial aldehyde dehydrogenase to acetate. Part of intracolonic acetaldehyde may also be absorbed to portal vein and be metabolized in the liver. The bacteriocolonic pathway offers a new explanation for the disappearance of a part of ethanol calories. Due to the low aldehyde dehydrogenase activity of colonic mucosa, acetaldehyde accumulates in the colon. Accordingly during ethanol oxidation highest acetaldehyde levels of the body are found in the colon and not in the liver. High intracolonic acetaldehyde may contribute to the pathogenesis of alcohol-induced diarrhoea. Because acetaldehyde is a carcinogen in experimental animals, it may also contribute to the increased risk of colon polyps and colon cancer, which have been found to be associated with heavy alcohol consumption. Intracolonic acetaldehyde may also be an important determinant of the blood acetaldehyde level and a possible hepatotoxin. In addition to acetaldehyde, gut-derived endotoxin is another potential candidate in the pathogenesis of alcohol-related liver injury. Experimental alcoholic liver injury has recently been prevented by antibiotics, and this effect was related to the prevention of endotoxin-induced activation of Kupffer's cells.


Definitive Radiation Therapy for Angiosarcoma of the Face and Scalp.
To examine the role of radiation therapy (RT) and factors' influence on tumor control for angiosarcoma of the face and scalp (AS-FS). We reviewed the records of 14 patients with histopathology proven AS-FS (median age=77 years) who underwent RT between 2000 and 2015. A total dose of 60 to 100 Gy was administered in 24 to 50 fractions. The median calculated biological effective dose (BED) was 93 Gy (range=63.25-120) based on α/β=10. The median follow-up was 16 months (range=5-62). Of the 14 patients, 8 patients (57%) experienced disease recurrence. The median overall survival (OS) rate was 31 months. The 1-year actuarial OS, event-free survival (EFS) and local control (LC) rates were 83%, 71% and 71%, respectively. In univariate analysis, age ≥78years was a significant prognostic factor for LC and OS. BED ≥95Gy was highly correlated with increased LC with borderline significance (p=0.06). Older patients had significantly lower survival rates and higher local recurrence rates than younger patients. The higher radiation dose may have a potential to improve local control for AS-FS.