Gadoxetic acid disodium-enhanced hepatocyte phase MRI: can increasing the flip angle improve focal liver lesion detection?
To determine whether hepatocyte phase gadoxetic acid disodium (EOB)-enhanced MRI using a high flip angle (FA) improves focal liver lesion (FLL) detection compared with using a standard low FA. Sixty-two consecutive patients with 159 FLLs underwent EOB-enhanced MRI during the hepatocyte phase at 5, 10, 15, and 20 min, with both low (10°) and high (30°) FAs. Two blinded radiologists independently and randomly reviewed the two image sets using a four-point rating scale. Sensitivities and specificities were calculated and lesion-to-liver contrast ratio (LLC) on all hepatocyte phase images was measured. The sensitivities with high FA for small (≤10 mm) malignant FLLs were significantly higher than those with low FA, at all time points, for both readers (P ≤ 0.05). Meanwhile, the specificities of the two protocols for the detection of all FLLs at all time points during the hepatocyte phase were high and same (98.2%) for both readers, without any significant differences (P = 1.00). LLCs with high FA were significantly higher than those with low FA at all time points (P ≤ 0.001). Hepatocyte phase EOB-enhanced MRI with increasing FA can significantly increase LLC and improve the detection of FLLs, particularly small malignant lesions.


Protein abundance of the cytokine receptor γc controls the thymic generation of innate-like T cells.
Innate-like T (iT) cells comprise a population of immunoregulatory T cells whose effector function is imposed during their development in the thymus to provide protective immunity prior to antigen encounter. The molecular mechanism that drives the generation of iT cells remains unclear. Here, we report that the cytokine receptor γc plays a previously unappreciated role for thymic iT cells by controlling their cellular abundance, lineage commitment, and subset differentiation. As such, γc overexpression on thymocytes dramatically altered iT cell generation in the thymus, as it skewed the subset composition of invariant NKT (iNKT) cells and promoted the generation of IFNγ-producing innate CD8 T cells. Mechanistically, we found that the γc-STAT6 axis drives the differentiation of IL-4-producing iNKT cells, which in turn induced the generation of innate CD8 T cells. Collectively, these results reveal a cytokine-driven circuity of thymic iT cell differentiation that is controlled by the abundance of γc proteins.


Suspended core photonic microcells for sensing and device applications.
In-line fiber-optic microcells are fabricated by postprocessing NKT LMA10 photonic crystal fibers. The cells are suspended core (SC) elements created by locally inflating some of the air holes while the core is being tapered. Based on a SC microcell with six air holes, a cantilever beam accelerometer is demonstrated. The microcells could also be used as gain and absorption cells for amplifier and spectroscopy applications.


Schoolchildren's knowledge of cervical cancer and smears.
A survey of 264 schoolchildren aged 15 and 16 in four Aberdeen schools revealed that 17% had never heard of cervical cancer or smears; proportionately more of the 244 were boys and were 15 years old. Of the other respondents, when asked to locate the cervix on an anatomical drawing, nearly three-quarters placed the cervix accurately or within the cervical canal. The same proportion knew that a cervical smear involved an internal examination. Not surprisingly, more girls than boys gave correct answers. The survey was carried out to assess the need for health education before the introduction of call-up for cervical cytology at the age of 20. It is recommended that further surveys of knowledge in older teenagers would be useful before effective health education programmes can be devised to ensure a high uptake of the new screening programme.


Low dose cyclophosphamide, alpha-interferon and continuous infusions of interleukin-2 in advanced renal cell carcinoma.
Pretreatment with a low dose of cyclophosphamide (CY) has been claimed to inhibit suppressor functions and augment various immune functions. A combination of a low dose of CY, alpha-interferon (IFN-alpha) and continuous infusion of interleukin-2 (IL-2) was used to treat patients with advanced renal cell cancer (RCC) (stage IV). Sixteen patients received four cycles consisting of CY (500 mg m-2) three days prior to daily i.m. injections of alpha-IFN (3 x 10(6) U), and continuous infusion of 18 x 10(6) IU rIL-2 for five days. The cycle interval was three weeks. Two patients had partial response (13%) (26+ and 12+ months), two had a minor response (9+ and 4 months), and three patients achieved stable disease (19+, 14+ and 8+ months). No patients required intensive care. Side effects were mainly fever, malaise, capillary leak syndrome and diarrhoea. Non-responders showed significantly higher eosinophil and platelet counts compared to responders. Serum concentration of IL-2 was significantly higher in responders. 5/11 patients had abnormally low values of serum thyroxine after therapy. Two patients needed thyroid hormone substitution. The difference between the initial and the lowest thyroxine values correlated significantly to survival (p < 0.03). The addition of CY to rIL-2 and IFN-alpha in the present protocol did not contribute to an increased major response rate.


Pacemaker Malfunction-Review of Permanent Pacemakers and Malfunctions Encountered in the Emergency Department.
Pacemaker malfunction refers to a failure of the pacemaker to perform the desired cardiac pacemaking function. These malfunctions can occur anywhere within the system from the pulse generator and leads to the electrode-myocardium interface. These failures of sensing, capture, and inadequate pacing can have severe hemodynamic consequences, so rapid identification of specific dysfunction is critical to intervention and stabilization. Emergency providers should be aware of pacemaker components, function, basic programming, and types of malfunctions to adequately assess, stabilize, and disposition patients.


Cutaneous large B-cell lymphoma of the leg masquerading as a chronic venous ulcer.
We report on a 74-year-old female patient with a primary cutaneous CD20+, diffuse large cell B-cell lymphoma of the lower leg resembling a chronic non-healing leg ulcer. There was no evidence of systemic involvement on computed tomography (CT) scans of the chest, abdomen and pelvis; a slightly enlarged lymph node in the right groin showed dermatopathic lymphadenopathy on histology and immunohistochemistry. Involvement of the bone marrow and peripheral blood was ruled out by punch biopsy and fluorescent activated cell sorter (FACS) analysis of the blood, respectively. Therapeutic anti-CD20 monoclonal antibody rituximab was given at 375 mg m(-2) i.v. once weekly for 7 weeks, without adverse effects, resulting in a minor improvement in the centre of the ulcerated tumour. Unfortunately, the response was not maintained, and after 7 weeks of treatment the patient started to develop new tumour lesions at the border of the ulcer. Local radiotherapy was started and combined photon and electron beam irradiation induced complete remission of the B-cell lymphoma.


Directed differentiation of human pluripotent stem cells into epidermal keratinocyte-like cells.
The human pluripotent stem cell (hPSC) differentiation has allowed for the generation of in vitro models to study human diseases in a dish. This protocol describes the generation of keratinocyte-like cells from hPSCs in chemically defined media. Treating hPSCs with retinoic acid and BMP4 induced the generation of keratinocyte progenitors, which further differentiated into mature keratinocytes in the presence of calcium. The keratinocytes generated with this protocol could be used to study keratinocyte biology, drug screening, and skin-related diseases. For complete details on the use and execution of this protocol, please refer to Ali et al. (2020).


Advances in biomarkers of biliary tract cancers.
Tumor biomarkers can be applied for early diagnosis or precise treatment, thereby leading to personalized treatment and better outcomes. Biliary tract cancers (BTCs) are a group of cancers that occurs in different locations and have different clinical or genetic properties. Though the incidence of BTCs is rare, BTCs are among the most lethal cancers in the world and all have very low 5-year survivals. Lack of efficient early diagnostic approaches or adjuvant therapies for BTCs are main reasons. These urge us to broaden the researches into BTC biomarkers. Although few progresses of diagnostic biomarkers for BTCs have been achieved, there are still some advances in prognostic, predictive and therapeutic areas. In this review, we will focus on these achievements.


Roles of naofen, a novel WD-repeat-2 protein, in the CCl4-treated livers--a possible relationship to cell proliferation.
Naofen (GenBank accession no. EF613262), a newly found intracellular protein in the WD-repeat-2 protein family, has been cloned as an anti-verotoxin II antibody immunoreactive substance, and the nucleotide- and amino acid-sequences have been clarified. The present study was undertaken to evaluate the roles of naofen especially in carbon tetrachloride (CCl4-induced cirrhosis model of rats, also in partial hepatectomy. Naofen mRNA expressions were observed from the early phases of cirrhosis development and during regenerative phases after partial hepatectomy, more remarkable in the former. Naofen immunoreactive fragments located in the vascular endothelial cells and peri-vascular spaces in normal livers especially in Glisson's areas, being strongly stained in the connective tissues 8 weeks after starting CCl4-injections, besides in the cytoplasm of hepatocytes in pseudo-lobules. In contrast, partial hepatectomy caused a small increase of naofen expressions in the whole hepatocytes, and significantly in the endothelial cells of portal veins and hepatic arterioles. Furthermore, in parallel to the degree of naofen mRNA and protein expressions, the rates of double-nuclei cells to total hepatocytes in the Glisson's areas increased in both cirrhosis and partial hepatectomy, suggesting a relationship between naofen expression and mitosis. In in-vitro studies with cell lines, vascular endothelial growth factor, a cell proliferation stimulant, increased the naofen mRNA expressions in HepG(2) cell lines, whereas paclitaxel, a cytotoxic anti-cancer drug, diminished them in NRK52E, both concentration-dependently. These results indicated that naofen immunoreactive fragments play an important role in the cell proliferation, relevant for analyzing the regenerative phases during cirrhosis developments and after partial hepatectomy.


A new finite element model of intra-articular impacted fragment in posterior malleolar fractures: A technical note.
Intra-articular impacted fragment (IAIF) was considered as the articular surface fragment resulting from impact and compressive forces. Malreduction of IAIF in posterior malleolar fractures was associated with the cause of talus subluxation and long-term arthritis. The effect of IAIF on ankle pressure and stress has not been studied, and it's difficult to do this in cadaver bone. So we established IAIF defect finite element model in posterior malleolar fractures and explored the effect of IAIF defect in ankle joint. We also discussed the relation between IAIF defect and post-traumatic arthritis.


Effects of butylated hydroxytoluene pretreatment on the metabolism and genotoxicity of aflatoxin B1 in primary cultures of adult rat hepatocytes: selective reduction of nucleic acid binding.
To elucidate biochemical mechanisms underlying the anticarcinogenic activity of butylated hydroxytoluene (BHT), studies were undertaken to characterize the influence of BHT pretreatment on the metabolism and genotoxicity of aflatoxin B1 (AFB1) in primary cultures of rat hepatocytes. During a 10-day pretreatment period, adult male rats were fed either a control diet or a diet supplemented with 0.5% BHT. Hepatocytes were subsequently isolated from each animal and cultured in chemically defined medium. Cultures prepared from rats which had been fed BHT metabolized AFB1 more rapidly than did controls. BHT pretreatment also enhanced oxidation of AFB1 to aflatoxin M1 (AFM1), and accelerated the rate of AFM1 conjugation. Covalent binding to DNA and RNA in BHT-pretreated cultures was reduced by 91 and 82%, respectively, while protein binding decreased by only 29%. AFB1 did not stimulate detectable DNA repair synthesis in BHT-pretreated cultures, although stimulation of DNA repair was clearly evident in control cultures. In a separate experiment, consistently higher baseline concentrations of reduced glutathione were observed in BHT-pretreated cells, indicating that BHT pretreatment may enhance formation of detoxified glutathione conjugates of AFB1. These findings suggest that the anticarcinogenic activity of BHT is due in part to preferential enhancement of hepatic detoxification mechanisms, with the result that intracellular concentrations of reactive metabolites are reduced and fewer covalently bound adducts are formed.


Hydrophobic cluster analysis: an efficient new way to compare and analyse amino acid sequences.
A new method for comparing and aligning protein sequences is described. This method, hydrophobic cluster analysis (HCA), relies upon a two-dimensional (2D) representation of the sequences. Hydrophobic clusters are determined in this 2D pattern and then used for the sequence comparisons. The method does not require powerful computer resources and can deal with distantly related proteins, even if no 3D data are available. This is illustrated in the present report by a comparison of human haemoglobin with leghaemoglobin, a comparison of the two domains of liver rhodanese (thiosulphate sulphurtransferase) and a comparison of plastocyanin and azurin.


The interaction between sense of mastery, social support, and parental distress among mothers with and without serious mental illness.
Social support and sense of mastery are considered important resources in coping both with serious mental illness (SMI) and with motherhood-related challenges. However, their interactive effects on the parental stress of mothers with SMI are not clear. Scales assessing parental distress, social support, and sense of mastery were administered to 60 mothers with SMI and 60 mothers without SMI. A main effect of sense of mastery and a lack of main effect of social support were found in both groups. An interaction effect of social support with mastery was found among mothers with SMI revealing that for mothers who had a high sense of mastery, social support was beneficial, whereas for mothers who had a low sense of mastery, social support was harmful. In practice, attention should be given to the sensitive provision of support, balancing between what is needed and what is requested, with the aim of not harming an individual's sense of mastery.


Characterization of Mg2+-ATPase activity in isolated B16 murine melanoma melanosomes.
B16 murine melanoma melanosomes were purified using sucrose density gradient centrifugation. ATPase activity was evaluated in presence of specific ATPase inhibitors, and compared with melanosome ATP-driven proton translocating activity in the melanosome. Mg2+ dependent ATPase activity was greatly inhibited (82%) by the specific inhibitors of vaculor proton translocating ATPase; Cis-didimethylsulfoxide dichloroplatinum (II) at approximately 90 microM and bafilomycin AI at two fold higher concentrations. Less inhibition, about 30 and 45% was obtained with N, N1-dicyclohexylcarbodiimide and N-ethylmaleimide, and the maximal effect occurred in the 50-100 microM and 0.1-1.5 mM ranges, respectively. These drugs at similar concentrations also inhibited the proton pumping activity to the same extent as observed for ATPase activity and half-maximal inhibition of each activity was found at nearly similar concentrations. Carbonylcyanide p-trifluoromethoxyphenyl hydra zone (FCCP) prevented ATP from setting up a pH gradient across the melanosomal membrane but stimulated Mg2+ ATPase activity significantly. Replacement of 5 mM Mg2+ with equimolar Ca2+ brought about a 60% inhibition in divalent cation-dependent ATPase- activity, and an 85% inactivation of ATP-linked melanosomal H+ pump activity. In the presence of optimal concentrations of Ca2+ and Mg2+ ATPase activity was similar to that seen in a Mg2+ medium. In Ca2+ medium ATPase activity was inhibited by CDDP and stimulated by FCCP, however these effects were two to three fold less than those observed in Mg2+ medium. FCCP failed to stimulate ATPase activity in CDDP- supplemented medium, thus suggesting that the same ATPase activity fraction was sensitive to both CDDP and FCCP. Mg2+-ATPase activity, like the proton-pump was anion dependent. The lowest activity was recorded in F medium, and increased in the order of F < So4(2-) < CL- = Br-. These results show that the ATPase activity may be related to the melanosomal proton pump.


Meeting the family: promoting humanism in gross anatomy.
Human dissection commonly occurs early in the undergraduate medical school curriculum, thus presenting an immediate opportunity for educators to teach and encourage humanistic qualities of respect, empathy, and compassion. The purpose of this study was to measure the impact of the Donor Luncheon, a unique program in which medical students meet the families of the anatomical donor prior to dissection in the anatomy course at the University of Oklahoma College of Medicine. Students were randomized into groups of 8 to attend the luncheon and either met with family of the donor or attended the luncheon with no donor family present. A questionnaire measured students' attitudes at 2 weeks, 6 weeks, and at the conclusion of the anatomy course. Factor analysis revealed 5 scales. Analysis revealed statistically significant differences across time for Donor as Person, Dissection Process, and Donor as Patient and statistically significant differences between groups for Donor as Person and Donor as Patient. These results suggest that this program can provide students with the opportunity to maintain more humanistic attitudes at the beginning of their medical education career.


Nor-MDP, saponin, corynebacteria, and pertussis organisms as immunological adjuvants in experimental malaria vaccination of macaques.
Vaccination of primates against malaria using antigen derived from erythrocytic parasite stages has been most successful where Freund's complete adjuvant has been employed. Since this adjuvant is clinically unacceptable its replacement is a matter of urgency.In the present work a muramyldipeptide derivative (nor-MDP) given in mineral oil has proved to be partially effective as an adjuvant for merozoite vaccination of Macaca mulatta against Plasmodium knowlesi, and saponin has proved to be effective in similar vaccination of M. fascicularis.


The laboratory diagnosis of pneumonia. The role of the community hospital pathologist.
Pneumonia is one of the most serious infections seen in community hospital practice, with virulent bacteria and viruses producing infections in the healthy host and a variety of opportunistic organisms capable of causing disease in the immunocompromised patient. Accurate laboratory diagnosis is extremely important for correct clinical management of pneumonia, and the community hospital pathologist can take an active role in daily review of respiratory tract specimens to optimize and coordinate this important laboratory testing. This article discusses strategies for improving sputum Gram stain interpretation and for the use of both routine and supplementary cultures in community-acquired pneumonias and outlines a comprehensive consultative approach for rapid and reliable pneumonia diagnosis in the compromised patient.


Structure, function, and evolution of plant NIMA-related kinases: implication for phosphorylation-dependent microtubule regulation.
Microtubules are highly dynamic structures that control the spatiotemporal pattern of cell growth and division. Microtubule dynamics are regulated by reversible protein phosphorylation involving both protein kinases and phosphatases. Never in mitosis A (NIMA)-related kinases (NEKs) are a family of serine/threonine kinases that regulate microtubule-related mitotic events in fungi and animal cells (e.g. centrosome separation and spindle formation). Although plants contain multiple members of the NEK family, their functions remain elusive. Recent studies revealed that NEK6 of Arabidopsis thaliana regulates cell expansion and morphogenesis through β-tubulin phosphorylation and microtubule destabilization. In addition, plant NEK members participate in organ development and stress responses. The present phylogenetic analysis indicates that plant NEK genes are diverged from a single NEK6-like gene, which may share a common ancestor with other kinases involved in the control of microtubule organization. On the contrary, another mitotic kinase, polo-like kinase, might have been lost during the evolution of land plants. We propose that plant NEK members have acquired novel functions to regulate cell growth, microtubule organization, and stress responses.


Effects of first-generation antipsychotics versus second-generation antipsychotics on quality of life in schizophrenia: a double-blind, randomised study.
Whether or not second-generation antipsychotics (SGAs) represent an advantage over first-generation antipsychotics (FGAs) in the treatment of schizophrenia is not certain. Effectiveness studies published in the past 10 years have not unequivocally confirmed the superiority of SGAs over FGAs. We aimed to compare quality of life in patients with schizophrenia on an FGA strategy with those on an SGA strategy. In the multicentre, randomised, double-blind Neuroleptic Strategy Study (NeSSy), we recruited participants (aged 18-65 years) with schizophrenia (ICD-10: F20.X) who required treatment initiation or a change in treatment, from 14 psychiatric university hospitals and state hospitals in Germany. Double randomisation allowed for restricted selection of a treatment within each antipsychotic drug group (FGA or SGA) for an individual patient: first, patients were assigned with a random number table to two of six possible drug pairs, each pair consisting of an FGA (haloperidol [3-6 mg] or flupentixol [6-12 mg]) given orally and an SGA (aripiprazole [10-20 mg], olanzapine [10-20 mg], or quetiapine [400-800 mg]) given orally, and the investigator then selected which pair was best suited to the patient; a second, double-blind random assignment allocated either the FGA or the SGA from the investigator-chosen pair to the patient. Treatment duration was 24 weeks. Primary outcomes were change from baseline to week 24 in quality of life (SF-36) and clinical global impression (CGI-I), analysed in all randomly assigned patients who received at least one dose of the study drug. Safety was assessed in a safety set, consisting of all randomly assigned patients who received at least one dose of the study drug, coinciding with the set of the efficacy analyses. The study is registered with ClinicalTrials.gov, number NCT01164059; German Clinical Trials Register, number DRKS00000304; WHO ICTRP, number U1111-1112-9727; and EudraCT, number 2009-010966-47. Between April 1, 2010, and May 31, 2013, 149 patients were randomly assigned, 69 to FGA treatment and 80 to SGA treatment. 136 patients received at least one dose of study drug (63 in the FGA group, 73 in the SGA group). Mean area under the curve (AUC) values of SF-36 were significantly higher in the SGA group than in the FGA group (85·1 [SD 14·7] vs 79·7 [17·3], p=0·0112). Mean AUC values for CGI-I scores decreased in both groups, but were not significantly different between the two groups (3·39 [SD 0·89] in the FGA group vs 3·26 [0·92] in the SGA group, p=0·3423). 30 (48%) of 63 patients given FGAs had at least one adverse event compared with 42 (57%) of 73 patients given an SGA (p=0·3019); the most common were nervous system disorders (18 [60%] of 30 in the FGA group vs 19 [45%] of 42 in the SGA group) and psychiatric disorders (ten [33%] vs 16 [38%]). One patient died after cessation of study drug (olanzapine), most likely as a result of an illicit drug overdose. The increase in body-mass index (BMI) was significantly higher in the SGA group than in the FGA group (p=0·0021 at week 6 and p=0·0041 at week 24). Improvement of patient-reported quality of life was significantly higher in patients with schizophrenia given SGAs than in those given FGAs, when treatment selection was individualised. This advantage, however, has to be weighed against the potential metabolic adverse effects of some SGAs. German Federal Ministry of Education and Research.


Pickering emulsions stabilized by colloidal gel particles complexed or conjugated with biopolymers to enhance bioaccessibility and cellular uptake of curcumin.
The aim of this study was to investigate the fate of curcumin (CUR)-loaded Pickering emulsions with complex interfaces during in vitro gastrointestinal transit and test the efficacy of such emulsions on improving the bioaccessibility and cellular uptake of CUR. CUR-loaded Pickering emulsions tested were whey protein nanogel particle-stabilized Pickering emulsions (CUR-EWPN) and emulsions displaying complex interfaces included 1) layer-by-layer dextran sulphate-coated nanogel-stabilized Pickering emulsions (CUR-DxS+EWPN) and 2) protein+dextran-conjugated microgel-stabilized Pickering emulsions (CUR-EWPDxM). The hypothesis was that the presence of complex interfacial material at the droplet surface would provide better protection to the droplets against physiological degradation, particularly under gastric conditions and thus, improve the delivery of CUR to Caco-2 intestinal cells. The emulsions were characterized using droplet sizing, apparent viscosity, confocal and cryo-scanning electron microscopy, zeta-potential, lipid digestion kinetics, bioaccessibility of CUR as well as cell viability and uptake by Caco-2 cells. Emulsion droplets with modified to complex interfacial composition (i.e. CUR-DxS+EWPN and CUR-EWPDxM) provided enhanced kinetic stability to the Pickering emulsion droplets against coalescence in the gastric regime as compared to droplets having unmodified interface (i.e. CUR-EWPN), whereas droplet coalescence occurred in intestinal conditions irrespective of the initial interfacial materials. A similar rate and extent of free fatty acid release occurred in all the emulsions during intestinal digestion (p > 0.05), which correlated with the bioaccessibility of CUR. Striking, CUR-DxS+EWPN and CUR-EWPDxM significantly improved cellular CUR uptake as compared to CUR-EWPN (p < 0.05). These results highlight a promising new strategy of designing gastric-stable Pickering emulsions with complex interfaces to improve the delivery of lipophilic bioactive compounds to the cells for the future design of functional foods.


[Effects of Outpatient Compact Rehabilitation on Physical Performance and Quality of Life in Patients with Work-Related Lung Diseases].
In Germany, pulmonary rehabilitation (PR) traditionally takes place in rehabilitation clinics. According to the current German guideline "Diagnostics and assessment of asbestos-related occupational diseases", PR can also be offered as outpatient program with the essential elements of inpatient PR (compact rehabilitation [CR]). Our project investigated the effects of CR regarding acceptance, physical performance, and quality of life of patients with occupational lung diseases. CR included 24 units of 90 minutes each with physiotherapy and breathing therapy as well as device-supported strength and endurance training. The aim of our study was to investigate the effects of CR in subjects with occupational diseases of the respiratory system and a legally anchored right to PR. Randomization was therefore not planned. A total of 148 insured persons with a confirmed occupational disease of the respiratory system were invited to participate by the employers' liability insurance association; 126 patients (85 %) accepted the invitation, and 78 participants (mean age: 71 years) completed the entire program (53 %). Benign asbestos-related diseases (plaques, pleural thickening, asbestosis) dominated with around 80 %. Ailments, depression, and dementia were typical obstacles. No adverse events occurred with strict observance of the chosen inclusion and exclusion criteria and training conditions. The measurement results at enrolment were compared with those at completion of the CR. CR led to a significant (p < 0.01) improvement in all parameters of physical performance: 6-minute walking test: + 36 m, ergometer test: + 9 watts, hand dynamometry: + 29 N, quadriceps strength test: + 84 MKI. The inspiratory capacity of the respiratory muscles (Pimax: + 1.1 kPa) also improved (p < 0.01). The SF-36 showed an improvement in quality of life (p < 0.05) in the subdomains "mental well-being" (+ 3.7) and "physical role function" (+ 4.2). Therefore, CR proves to be a safe therapy if the inclusion and exclusion criteria are adhered to. CR is widely accepted by patients without severe comorbidities and achieves positive effects comparable to those that have been demonstrated in rehabilitation clinics. Outpatient CR is therefore suitable for eliminating the lack of structured and certified rehabilitation and training offers in rehabilitation clinics and for preserving the effects achieved there for insured patients with work-related respiratory and lung diseases.


Ultrasound evaluation of bladder calculi.
A case is presented in which the identification of intravesical calculi by ultrasound was an aid in management. Bladder stones appear as high intensity echoes within the bladder, have an associated acoustic shadow and shift to the dependent portion of the bladder with alterations in position. Ultrasound provides a rapid, safe imaging technique to diagnose or verify the presence of bladder calculi.


Combined p19Arf and interferon-beta gene transfer enhances cell death of B16 melanoma in vitro and in vivo.
Approximately 90% of melanomas retain wild-type p53, a characteristic that may help shape the development of novel treatment strategies. Here, we employed an adenoviral vector where transgene expression is controlled by p53 to deliver the p19 alternate reading frame (Arf) and interferon-β (IFNβ) complementary DNAs in the B16 mouse model of melanoma. In vitro, cell death was enhanced by combined gene transfer (63.82±15.30% sub-G0 cells); yet introduction of a single gene resulted in significantly fewer hypoploid cells (37.73±7.3% or 36.96±11.58%, p19Arf or IFNβ, respectively, P<0.05). Annexin V staining and caspase-3 cleavage indicate a cell death mechanism consistent with apoptosis. Using reverse transcriptase quantitative PCR, we show that key transcriptional targets of p53 were upregulated in the presence of p19Arf, although treatment with IFNβ did not alter expression of the genes studied. In situ gene therapy revealed significant inhibition of subcutaneous tumors by IFNβ (571±25 mm3) or the combination of p19Arf and IFNβ (489±124 mm3) as compared with the LacZ control (1875±33 mm3, P<0.001), whereas p19Arf yielded an intermediate result (1053±169 mm3, P<0.01 vs control). However, only the combination was associated with increased cell death and prolonged survival (P<0.01). As shown here, the combined transfer of p19Arf and IFNβ using p53-responsive vectors enhanced cell death both in vitro and in vivo.


Group A variants defined with a monoclonal anti-A reagent.
Unusual serologic findings mimicking the B(A) phenomenon were noted in two group B blood donors using blended murine monoclonal anti-A reagent. With additional studies, including a binding experiment using affinity chromatography, the presence of aberrant group A activities was confirmed. This observation suggests that persons with atypical B(A) phenotype may warrant further investigation to delineate the ABO blood group.


Fiber bragg grating strain sensor demodulation with quadrature sampling of a mach-zehnder interferometer.
A simple and highly sensitive phase-demodulation technique is proposed, and its use for a fiber Bragg grating strain sensor is experimentally demonstrated. Sampling a phase-modulated Mach-Zehnder output with controlled time delay produced two quadrature data streams that have relative quadrature phase difference (90 degrees ). The Bragg wavelength-dependent phase information is extracted by application of digital arctangent function and phase unwrapping to the quadrature signals. By use of this technique with a reference grating, strain sensing at as much as a 30-kHz sampling rate was obtained with strain resolution of 3.5 microstrains and 6 nanostrains/[square root]Hz in quasi-static and dynamic strain measurements, respectively.


Rate constants studies of the dye-sensitized photoinactivation of lysozyme.
The rate constants for the photodynamic inactivation of hen egg-white lysozyme at different temperatures were studied. Arrhenius plots of the methylene blue sensitized photo-inactivation of lysozyme gave an experimental activation energy of 7.5 kcal/mol. The rate constants for the photodynamic inactivation of lysozyme in the presence of riboflavin decreased almost linearly in the temperature range 4-38 degrees C. The photosensitized oxidation of lysozyme at -20 degrees C in freezing and non-freezing solvents was possible only in the presence of riboflavin. The effect of dye concentration on the quantum yield and rate constant for the photodynamic inactivation of lysozyme was examined. The quantum yields were lower when the concentrations of methylene blue used were low, and increased on increasing dye concentration, getting to a maximum and then declined at higher dye concentrations. It was found that in the case of riboflavin sensitized photo-inactivation of lysozyme both the rate constant and the quantum yield increased as the dye concentration increased. No maximum was observed over the range of dye concentrations studied. A new mechanism is postulated for the photodynamic action of lysozyme in the presence of riboflavin.


Effect of range of motion in heavy load squatting on muscle and tendon adaptations.
Manipulating joint range of motion during squat training may have differential effects on adaptations to strength training with implications for sports and rehabilitation. Consequently, the purpose of this study was to compare the effects of squat training with a short vs. a long range of motion. Male students (n = 17) were randomly assigned to 12 weeks of progressive squat training (repetition matched, repetition maximum sets) performed as either a) deep squat (0-120° of knee flexion); n = 8 (DS) or (b) shallow squat (0-60 of knee flexion); n = 9 (SS). Strength (1 RM and isometric strength), jump performance, muscle architecture and cross-sectional area (CSA) of the thigh muscles, as well as CSA and collagen synthesis in the patellar tendon, were assessed before and after the intervention. The DS group increased 1 RM in both the SS and DS with ~20 ± 3 %, while the SS group achieved a 36 ± 4 % increase in the SS, and 9 ± 2 % in the DS (P < 0.05). However, the main finding was that DS training resulted in superior increases in front thigh muscle CSA (4-7 %) compared to SS training, whereas no differences were observed in patellar tendon CSA. In parallel with the larger increase in front thigh muscle CSA, a superior increase in isometric knee extension strength at 75° (6 ± 2 %) and 105° (8 ± 1 %) knee flexion, and squat-jump performance (15 ± 3 %) were observed in the DS group compared to the SS group. Training deep squats elicited favourable adaptations on knee extensor muscle size and function compared to training shallow squats.


Automated segmentation and analysis of retinal microglia within ImageJ.
Microglia are immune cells of the central nervous system capable of distinct phenotypic changes and migration in response to injury. These changes most notably include the retraction of fine dendritic structures and adoption of a globular, phagocytic morphology. Due to their characteristic responses, microglia frequently act as histological indicators of injury progression. While algorithms seeking to automate microglia counts and morphological analysis are becoming increasingly popular, few exist that are adequate for use within the retina and manual analysis remains prevalent. To address this, we propose a novel segmentation routine, implemented within FIJI-ImageJ, to perform automated segmentation and cell counting of retinal microglia. We show that our routine could perform cell counts with accuracy similar to manual observers using the I307N Rho model. Tracking cell position relative to retinal vasculature, we observed population migration towards the photoreceptor layer beginning 12 h post light damage. Using feature selection with Chi2 and principal component analysis, we resolved cells along a morphological gradient, demonstrating that extracted features were sufficiently descriptive to capture subtle morphological changes within cell populations in I307N Rho and Balb/c TLR2-/- retinal degeneration models. Taken together, we introduce a novel automated routine capable of efficient image processing and segmentation. Using data retrieved following segmentation, we perform morphological analysis simultaneously on whole populations of cells, rather than individually. Our algorithm was built entirely with open-source software, for use on retinal microglia.


'Noticing' in health professions education: Time to pay attention?
Health professions education teaches students to notice particular things, but has given little attention to teaching 'noticing' as a form of personal inquiry. The former is self-evidently important, as it develops a way of seeing and behaving that is uniquely relevant to each health profession. Despite this emphasis, health professionals may fail to notice 'warning signs' in patients, be unaware of their own biases or develop unrecognised habits that have moved away from accepted standards. It has been suggested that such 'not noticing' is currently endemic. We situate our exploration of noticing in the mathematics and science education literature and John Mason's treatise on 'The discipline of noticing', differentiating between the observations that people make as they go about their lives ('ordinary' noticing), the specialised noticing that underpins professional expertise (Professional Noticing) and practices that can enhance the capacity to notice and to learn from experience (Intentional Noticing). We make the case for teaching health professions students about these conceptualisations of noticing, being able to notice with all our senses, and learning about the practices of Intentional Noticing in particular, which we suggest will have utility across health professional careers and personal lives. We acknowledge the difficulties in transferring heterogenous finding from one field to another but suggest that there are gains to be made in applying these noticing concepts to health professions education. We tentatively propose some strategies and activities for developing Professional Noticing and the practices of Intentional Noticing and link them to a new module that we are piloting with health professions students. As well as aiding health professionals sharpen their noticing abilities, reinvigorate their practice and interrogate assumptions that underpin health care, we suggest that ideas about 'noticing' may also help educators and researchers in the health professions reimagine their work.


Adsorption mechanism and dispersion efficiency of three anionic additives [poly(acrylic acid), poly(styrene sulfonate) and HEDP] on zinc oxide.
Adsorption on ZnO of sodium poly(acrylate) (PAA), sodium poly(styrene sulfonate) (PSS) and a monomer surfactant [hydroxyethylidene diphosphonate (HEDP)] was investigated in suspensions initially equilibrated at pH 7. Results demonstrate interplay in the adsorption mechanism between zinc complexation, salt precipitation, and ZnO dissolution. In the case of PAA, the adsorption isotherm exhibits a maximum attributed to the precipitation of zinc polyacrylate. PSS and HEDP formed high-affinity adsorption isotherms, but the plateau adsorption of HEDP was significantly lower than that of PSS. The adsorption isotherm of each additive is divided into two areas. At low additive concentration (high zinc/additive ratio), the total zinc concentration in the solution decreased and the pH increased upon addition. At a higher additive ratio, zinc concentration and pH increased with the organic concentration. The increase in pH is due to the displacement of hydroxyl ions from the surface and the increase in zinc concentration results from the dissolution of ZnO due to the complexation of zinc ions by the organics. The stability of the ZnO dispersions was investigated by measurement of the particle size distribution after addition of various amounts of polymers. The three additives stabilized the ZnO dispersions efficiently once full surface coverage was reached.


Identification and localization of talin in chick retinal pigment epithelial cells.
Retinal pigmented epithelial cells are adherent at their basal surface to Bruch's membrane and at their apical surface to the neural retina. We examined the expression and distribution of two proteins that are found in regions of cell-matrix interaction, talin and integrin. Talin is a 235-kDa cytoplasmic protein that has been localized to regions of cell-substrate adhesion. It binds to both integrin, a transmembrane glycoprotein complex, and to vinculin, a cytoskeletal protein. In the present study, we produced a polyclonal antibody to chicken gizzard talin. Using this antibody we showed by western blot analysis that talin is expressed by RPE cells and is found in the triton-soluble fraction. Talin was shown to co-localize with integrin and vinculin in the basal region of chick RPE cells isolated from 18-day-old chick embryos. Neither talin nor integrin was found in the apical processes or in the zonula adherens. Antibodies to vinculin showed staining both in the apical and basal regions of the RPE cells. The localization of integrin, talin and vinculin along the basal membrane suggests that this complex is important in the attachment of the RPE cells to the basement membrane. The distribution of integrin and talin was examined in primary cultures of RPE cells grown on permeable filters. In these cells, a polarized distribution of integrin and talin was not observed. This may suggest that the neural retina may be important for maintaining the differentiated state of the RPE cells.


Selenium Deficiency Affects Uterine Smooth Muscle Contraction Through Regulation of the RhoA/ROCK Signalling Pathway in Mice.
Selenium (Se) is considered one of the essential micronutrients for humans and animals, and its effects on physiological functions are multifaceted. In the present study, we investigated the effects of Se deficiency on uterine smooth muscle contraction in mice by studying G protein Rho (RhoA)/Rho kinase (ROCK) signalling pathway-related molecules. The α-sma in smooth muscle tissue of mice was determined. The extracorporeal contraction curve for uterine smooth muscle in mice was determined. Both of these results indicate that Se deficiency impairs the contractile ability of uterine smooth muscle in mice. The expression of mRNA was measured by real-time quantitative PCR. The results showed that there was no significant change in mRNA expression of RhoA, ROCK, myosin light chain phosphatase (MLCP), or myosin light chain (MLC) in tissues. The protein levels were detected by Western blot. The results showed that there were no significant differences in RhoA, ROCK, MLCP, or MLC expression. However, compared with the CG, the concentration of phosphorylated MLC (P-MLC) increased in the SG and the concentration of P-MLC decreased in the DG. The activity of ROCK and MLCP was tested by liquid scintillation. The results suggest that the lack of Se may affect the regulation of MLCP by ROCK. Cellular experiments were performed to compare with results from tissues. There was no significant difference between the two models. The results indicated that Se deficiency affects uterine smooth muscle contraction by regulating the RhoA/ROCK signalling pathway. As the concentration of Se decreases, the activity of MLCP increases, which promotes the dephosphorylation of P-MLC, causing a decrease in contraction.


The role of postoperative testosterone in repair of iatrogenic hypospadias in rabbits.
Testosterone administered preoperatively in hypospadiac children increases phallic size and improves skin vascularity. We histologically evaluated the role of postoperative testosterone in tissue remodeling in an animal model. Hypospadias was created in 18 rabbits and repaired with a preputial onlay graft. Animals were randomized to receive either one intramuscular (i.m.) dose of testosterone postoperatively (n=6), or 2 weeks of daily 1% topical testosterone (n=6). Control animals underwent the urethral operation, but received no testosterone (n=6). Penises were harvested at 2 and 5 weeks, and blindly assessed for collagen formation, re-epithelialization and fibrosis, and complications. Of the animals sacrificed at 2 weeks, those that received testosterone had a greater incidence of cuboidal epithelium (83%) versus controls (33%). In the 2-week group, animals receiving testosterone had increased fibrosis, periurethral and soft-tissue inflammation compared to controls. By 5 weeks, all differences in fibrosis and inflammation had resolved. No animal developed fistula or diverticulum. Of animals sacrificed at 2 weeks, 67% stained for BrdU, a DNA proliferative marker. At 5 weeks, no non-testosterone rabbit demonstrated positive staining, while 83% of those receiving testosterone were positive. There were no differences between animals that received topical and i.m. testosterone. Administration of testosterone following hypospadias repair in rabbits changes the histologic composition of the urothelium and leads to an exaggerated inflammatory response in the supportive stroma. Such treatment may prove a useful adjunct in patients undergoing complex genital reconstruction.


Medication for Gravid and Nursing Oral and Maxillofacial Surgery Patients.
The purpose of this article is to clarify clinically impactful features of the perioperative and postoperative pharmacologic management of pregnant and lactating patients in the maxillofacial or dental setting. Before prescribing any drug to a nursing mother or pregnant patient, the maxillofacial surgeon and other dental and medical providers should consider the available evidence, benefits, and risk for that particular drug. There are many complex factors to consider when prescribing in order to maintain the safety of the pregnant individual, fetus, and infant. This article aims to provide concise, memorable, and actionable information to use in your clinical practice.


Modeling adsorption with lattice Boltzmann equation.
The research of adsorption theory has recently gained renewed attention due to its critical relevance to a number of trending industrial applications, hydrogen storage and shale gas exploration for instance. The existing theoretical foundation, laid mostly in the early twentieth century, was largely based on simple heuristic molecular interaction models and static interaction potential which, although being insightful in illuminating the fundamental mechanisms, are insufficient for computations with realistic adsorbent structure and adsorbate hydrodynamics, both critical for real-life applications. Here we present and validate a novel lattice Boltzmann model incorporating both adsorbate-adsorbate and adsorbate-adsorbent interactions with hydrodynamics which, for the first time, allows adsorption to be computed with real-life details. Connection with the classic Ono-Kondo lattice theory is established and various adsorption isotherms, both within and beyond the IUPAC classification are observed as a pseudo-potential is varied. This new approach not only enables an important physical to be simulated for real-life applications, but also provides an enabling theoretical framework within which the fundamentals of adsorption can be studied.


Brain isoenzyme of creatine kinase. I. Purification of rabbit enzyme and production of specific antibodies.
Creatine kinase (EC 22.214.171.124) of rabbit brain (BB) was purified to hemogeneity as judged by sedimentation velocity analysis in the ultracentrifuge. Nevertheless, the purified enzyme contained as many as seven extraneous protein species when examined by disc electrophoresis in polyacrylamide gel. The purified preparation also showed antigenic heterogeneity when it reacted in agar gel double immunodiffusion analysis with antibodies produced against it in the rooster. At least some of the extraneous proteins appeared to arise from BB during storage. Subsequently BB was purified to hemogeneity by disc electrophoresis in polyacrylamide gel. It was excised from the gel and injected repeatedly with Freund's complete adjuvant into roosters. A single immunoprecipitin line was noted in agar gel double immunodiffusion analysis when partially pure enzyme reacted with the antibodies raised to the electrophoretically pure protein. These antibodies inhibited the enzymatic activity of BB in both soluble and insoluble immune complexes. They did not, however, form immunoprecipitates with or inhibit rabbit muscle (MM) or rabbit hybrid (MB) creatine kinases. The antibodies were therefore specific for BB and did not react with MM or MB.


Estimated number of adult survivors of childhood cancer in United States with cancer-predisposing germline variants.
To estimate the absolute number of adult survivors of childhood cancer in the U.S. population who carry a pathogenic or likely pathogenic variant in a cancer predisposition gene. Using the Surveillance, Epidemiology, and End Results (SEER) Program, we estimated the number of childhood cancer survivors on December 31, 2016 for each childhood cancer diagnosis, multiplied this by the proportion of carriers of pathogenic/likely pathogenic variants in the St. Jude Lifetime Cohort (SJLIFE) study, and projected the resulting number onto the U.S. Based on genome sequence data, 11.8% of 2450 SJLIFE participants carry a pathogenic/likely pathogenic variant in one of 156 cancer predisposition genes. Given this information, we estimate that 21 800 adult survivors of childhood cancer in the United States carry a pathogenic/likely pathogenic variant in one of these genes. The highest estimated absolute number of variant carriers are among survivors of central nervous system tumors (n = 4300), particularly astrocytoma (n = 1800) and other gliomas (n = 1700), acute lymphoblastic leukemia (n = 4300), and retinoblastoma (n = 3500). The most frequently mutated genes are RB1 (n = 3000), NF1 (n = 2300), and BRCA2 (n = 800). Given the increasing number of childhood cancer survivors in the United States, clinicians should counsel survivors regarding their potential genetic risk, consider referral for genetic counseling and testing, and, as appropriate, implement syndrome-specific cancer surveillance or risk-reducing measures.


The role of stem cell factor and c-KIT in keloid pathogenesis: do tyrosine kinase inhibitors have a potential therapeutic role?
Keloids are fibroproliferative disorders characterized by increased deposition of extracellular matrix components. Stem cell factor (SCF) and its receptor c-KIT are expressed in a wide variety of cells and have also been demonstrated to be important modulators of the wound healing process. To examine the role of the SCF/c-KIT system in keloid pathogenesis. Immunohistochemical staining and Western blot analyses were used to examine localization and expression of SCF and c-KIT in keloid and normal skin tissue. This was followed by the detection of SCF and c-KIT expression in fibroblasts cultured in vitro and fibroblasts exposed to serum. To investigate the effect of epithelial-mesenchymal interactions, a two-chamber system was employed in which keratinocytes on membrane inserts were cocultured with the fibroblasts. SCF and c-KIT expression levels in all cell extracts and conditioned media were assayed by Western blotting. In another set of experiments, the effect of imatinib (Glivec(®), Gleevec(®); Novartis Pharma AG, Basel, Switzerland) on keloid fibroblasts was examined. SCF and c-KIT were upregulated in keloid scar tissue and in cultured fibroblasts stimulated with serum, highlighting their importance in the initial phase of wound healing. We further demonstrated that epithelial-mesenchymal interactions, mimicked by coculture of keratinocytes and fibroblasts in vitro, not only stimulated secretion of the soluble form of SCF in keloid cocultures but also brought about shedding of the extracellular domain of c-KIT perhaps by upregulation of tumour necrosis factor-α converting enzyme which was also upregulated in keloid scars in vivo and keloid cocultures in vitro. In addition keloid cocultures expressed increased levels of phosphorylated c-KIT highlighting an activation of the SCF/c-KIT system. Finally, we demonstrated that imatinib, a tyrosine kinase inhibitor, may be a possible therapeutic agent for keloids. These data indicate that the SCF/c-KIT system plays an important role in scar pathogenesis, and underscore the role of imatinib as a key therapeutic agent in keloid scars.


The role of PKC signaling in CRF-induced modulation of startle.
Hypersignaling of corticotropin releasing factor (CRF) has been implicated in stress disorders; however, many of its downstream mechanisms of action remain unclear. In vitro, CRF1 receptor activation initiates multiple cell signaling cascades, including protein kinase A (PKA), protein kinase C (PKC), and mitogen-activated protein kinase kinase MEK1/2 signaling. It is unclear, however, which of these signaling cascades mediate CRF-induced behaviors during stress. We examined the role of PKA, PKC, and MEK1/2 signaling pathways in CRF-induced anxiety as measured by startle hyperreactivity. Mice treated with intracerbroventricular (ICV) ovine CRF (oCRF) were pretreated with the PKA inhibitor Rp-cAMPS, PKC inhibitor bisindolylmaleimide (BIM), or MEK1/2 inhibitor PD98059 (ICV) and assessed for acoustic startle reactivity. The PKC inhibitor BIM significantly attenuated CRF-induced increases in startle. BIM was also able to block startle increases induced by oCRF when both compounds were infused directly into the bed nucleus of stria terminalis (BNST). PKA and MEK1/2 inhibition had no significant effects on CRF-induced changes in startle at the dose ranges tested. CRF-induced disruption of prepulse inhibition was not significantly reversed by any of the three pretreatments at the dose ranges tested. PKC signaling is required for CRF-induced increases in startle, and this effect is mediated at least in part at the BNST. These findings suggest that PKC signaling cascades (1) may be important for the acute effects of CRF to induce startle hyperreactivity and (2) support further research of the role of PKC signaling in startle abnormalities relevant to disorders such as posttraumatic stress disorder.


Prospective comparison of search strategies for systematic reviews: an objective approach yielded higher sensitivity than a conceptual one.
In the development of search strategies for systematic reviews, "conceptual approaches" are generally recommended to identify appropriate search terms for those parts of the strategies for which no validated search filters exist. However, "objective approaches" based on search terms identified by text analysis are increasingly being applied. To prospectively compare an objective with a conceptual approach for the development of search strategies. Two different MEDLINE search strategies were developed in parallel for five systematic reviews covering a range of topics and study designs. The Institute for Quality and Efficiency in Health Care (IQWiG) applied an objective approach, and external experts applied a conceptual approach for the same research questions. For each systematic review, the citations retrieved were combined and the overall pool of citations screened to determine sensitivity and precision. The objective approach yielded a weighted mean sensitivity and precision of 97% and 5%. The corresponding values for the conceptual approach were 75% and 4%. Our findings indicate that the objective approach applied by IQWiG for search strategy development yields higher sensitivity than and similar precision to a conceptual approach. The main advantage of the objective approach is that it produces consistent results across searches.


Plasmodium falciparum SSB tetramer wraps single-stranded DNA with similar topology but opposite polarity to E. coli SSB.
Single-stranded DNA binding (SSB) proteins play central roles in genome maintenance in all organisms. Plasmodium falciparum, the causative agent of malaria, encodes an SSB protein that localizes to the apicoplast and likely functions in the replication and maintenance of its genome. P. falciparum SSB (Pf-SSB) shares a high degree of sequence homology with bacterial SSB proteins but differs in the composition of its C-terminus, which interacts with more than a dozen other proteins in Escherichia coli SSB (Ec-SSB). Using sedimentation methods, we show that Pf-SSB forms a stable homo-tetramer alone and when bound to single-stranded DNA (ssDNA). We also present a crystal structure at 2.1 Å resolution of the Pf-SSB tetramer bound to two (dT)(35) molecules. The Pf-SSB tetramer is structurally similar to the Ec-SSB tetramer, and ssDNA wraps completely around the tetramer with a "baseball seam" topology that is similar to Ec-SSB in its "65 binding mode". However, the polarity of the ssDNA wrapping around Pf-SSB is opposite to that observed for Ec-SSB. The interactions between the bases in the DNA and the amino acid side chains also differ from those observed in the Ec-SSB-DNA structure, suggesting that other differences may exist in the DNA binding properties of these structurally similar proteins.


Studies in genetically modified mice implicate maternal HDL as a mediator of fetal growth.
Studies in humans have shown a direct association between maternal plasma cholesterol concentrations and infant birthweight. Similarly, previous studies in our laboratory have shown that chow-fed mice lacking apolipoprotein (apo) A-I, the major protein in HDL, have low HDL-cholesterol (HDL-C) concentrations and smaller fetuses in midgestation. In the current study, we measured fetal weights in mice with varying levels of apoA-I gene dose (knockout, wild-type, and transgenic) and examined metabolic pathways known to affect fetal growth. As expected, we found the differences in apoA-I expression led to changes in HDL particle size and protein cargo as well as plasma cholesterol concentrations. Fetal masses correlated directly with maternal plasma cholesterol and apoA-I concentrations, but placental masses and histology did not differ between groups of mice. There was no significant difference in glucose or amino acid transport to the fetus or in expression levels of the glucose (glucose transporter 1 and 2) or amino acid (sodium-coupled neutral amino acid transporter 1 and 2) transporters in whole placentas, although there was a trend for greater uptake of both nutrients in the whole fetal unit (fetus + placenta) of mice with greater apoA-I levels; significant differences in transport rates occurred when mice without apoA-I (knockout) vs. mice with apoA-I (wild-type and transgenic) were compared. Glucose tolerance tests were improved in the mice with the highest level of apoA-I, suggesting increased insulin-induced uptake of glucose by tissues of apoA-I transgenic mice. Thus, maternal HDL is associated with fetal growth, an effect that is likely mediated by plasma cholesterol or other HDL-cargo, including apolipoproteins or complement system proteins. A direct role of enhanced glucose and/or amino acid transport cannot be excluded.-Rebholz, S. L., Melchior, J. T., Davidson, W. S., Jones, H. N., Welge, J. A., Prentice, A. M., Moore, S. E., Woollett, L. A. Studies in genetically modified mice implicate maternal HDL as a mediator of fetal growth.


[Effects of blinding by bilateral orbital enucleation on the ultrastructure of the pineal gland in the female garden dormouse (Eliomys quercinus L.). Correlations with the hypothalamo-pituitary-ovarian axis].
Dormice were blinded by bilateral enucleation in December before hibernation or in March at the end of hibernation and were then studied in July and October. All the animals stayed in permanent anoestrus even at long-term. The ultrastructure of the pinealocyte was very characteristic, presenting typical elements of both hibernal anoestrus and sexual activation. Two organelles were well developed in enucleated dormice: reticulo-endoplasmic vacuoles and liposomes whose development seemed to be associated with protein secretions and pineal serotonine level, respectively. The hypothalamo-hypophyseal characterististics of the enucleated animals were also surprising: the hypothalamic LHRH load was important and hypophyseal gonadotropic cell development normal although the ovaries were hypoactive. The dormouse has a seasonal sexual cycle which cannot be realized without light. Pineal ultrastructural findings correlated with the activity of the hypothalamo-pituitary-ovarian axis lead us to think that this endocrine gland plays a role in the action of light on sexual activity.


Pear-shaped bladder caused by large iliopsoas muscles.
A case of pear-shaped bladder resembling pelvic lipomatosis was shown to be caused by large iliacus and psoas muscles.


First trimester pregnancy loss after fresh and frozen in vitro fertilization cycles.
To characterize risks for early pregnancy loss after fresh and frozen IVF cycles and to investigate whether risk is modified by infertility diagnoses or transfer of embryos in fresh versus frozen cycles. Retrospective cohort study using data from the National Assisted Reproductive Technology (ART) Surveillance System. Fertility centers. Clinical pregnancies achieved with fresh and frozen IVF cycles between 2007 and 2012 (N = 249,630). None. First trimester pregnancy loss. A diagnosis of uterine factor was associated with an increased risk of loss in women aged 40 years and younger (<30 years: adjusted risk ratio (aRR) = 1.24, 95% confidence interval (CI) 1.04-1.48; 30-34 years: aRR = 1.27, 95% CI 1.17-1.38; 35-37 years: aRR = 1.12, 95% CI 1.03-1.21; 38-40 years: aRR = 1.08, 95% CI 1.01-1.17). There was an increased risk of loss in women with diminished ovarian reserve aged 30-34 years (aRR = 1.08, 95% CI 1.01-1.15) and in women with ovulatory dysfunction younger than 35 years (<30 years: aRR = 1.12, 95% CI 1.05-1.19; 30-34 years: aRR = 1.07, 95% CI 1.02-1.13). There was an increased risk of loss after frozen ETs versus fresh among women younger than 38 years, but this remained significant in the subanalysis of similar quality embryos only in women younger than 30 years (aRR = 1.16, 95% CI 1.04-1.32). Uterine factor had the largest increased risk of loss among infertility diagnoses, although the magnitudes of all risks were small. When transferring embryos of similar quality, the risks of loss were similar between fresh and frozen cycles.


Effect of starvation on renal metabolism in the rat.
The effects of starvation on the acid-base status of the rat and on the glucoeogenic and ammoniagenic capacity of rat renal-cortical slices were examined. Starvation for 48 or 72 hr did not affect acid-base status, and urinary ammonia production did not change. Kidney cortical slices from starved as compared to fed rats showed increased gluconeogenic capacity when incubated with the substrated pyruvate, succinate, fumarate, malate, 2-oxyoglutarate, glutamine and glutamate. Renal cortical tissue from starved rats also had increased activity of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase. Renal cortical slices from starved rats did not differ from those from fed rats in the ability to produce ammonia from glutamine or glutamate, nor was there any difference inhe activity of glutaminase between these groups. These results show that renal gluconeogenic capacity is increased in starved rats in the absence of systemic acidosis, and starvation does not lead to an increase in urinary ammonia excretion or renal ammoniagenic capacity.


Techniques for right and left ventricular endomyocardial biopsy.
Right ventricular endomyocardial biopsy using percutaneous right internal jugular approach proved a safe and easily performed technique in more than 1,300 procedures. Adequate tissue was obtained in more than 98 percent of patients and morbidity rate was remarkably low. Other approaches to the right ventricle may be used, but retrograde left ventricular endomyocardial biopsy appears to be the safest and most reliable alternative to transjugular right ventricular biopsy. The safety and success of the techniques for right and left heart biopsy described depend on meticulous attention to methodologic detail.


Expressions of three cotton genes encoding the PIP proteins are regulated in root development and in response to stresses.
Cotton (Gossypium hirsutum), the most important textile crop worldwide, often encounters water stress such as drought or waterlog during its growth season (Summer). To investigate molecular mechanism of water regulation in cotton plants, three cDNAs encoding the plasma membrane intrinsic protein (PIP) were isolated from cotton root cDNA library, and designated GhPIP1;1, GhPIP2;1 and GhPIP2;2, respectively. All of the three PIP proteins displayed water channel activity in Xenopus laevis oocytes. GhPIP2;1 and GhPIP2;2 proteins, however, showed much higher water transport activity than that of the GhPIP1;1 protein. Northern blot analysis revealed that all of the three genes were preferentially expressed in young roots. Further analysis by Real-time quantitative RT-PCR revealed that the transcripts of all the three genes were accumulated at high levels in 3-day-old young roots, but dramatically declined to much lower levels in 6-14 days old roots during seedling development, suggesting that expressions of the isolated GhPIP genes are developmentally regulated in roots. Additionally, expressions of the three genes were remarkably up-regulated or down-regulated under different stresses such as NaCl, cold, PEG (polyethylene glycol) treatments. Collectively, the results suggest that these genes may be involved in root development and in response to stresses.


The prevalence of abnormal results of conventional coagulation tests on admission to a trauma center.
Several groups have reported that a fraction of severely injured patients have abnormal coagulation tests at presentation to trauma centers, even in the absence of significant crystalloid resuscitation. These patients have high mortality, but their prevalence in trauma populations is not clear from the reports. Records of all patients admitted to a large urban trauma center during 2000 through 2006 were searched for early measures of common coagulation tests and in-hospital mortality. Abnormal coagulation tests were increasingly frequent with increasing injury severity, ranging from 5 to 43 percent for the prothrombin time as the injury severity scores (ISSs) increased from 5 to more than 45 and 4 to 18 percent for platelet counts of less than 150 x 10(9) per L. Abnormal coagulation tests were associated with excess mortality even below conventional transfusion triggers and this was especially true for the partial thromboplastin time. Abnormal coagulation tests are common in severely injured patients. Even in the moderately injured, they are associated with higher mortality.


Stenotic aortic and mitral valves in three adult brothers with arthrogryposis multiplex congenita.
Three brothers with arthrogryposis multiplex congenita survived into adulthood. In their fourth decade, the clinical course for each brother became complicated by severe stenoses of their aortic and mitral valves. One brother died suddenly, and the remaining 2 developed heart failure. requiring valvular replacement.


Concentration and prevalence of Escherichia coli O157 and Salmonella serotypes in sheep during slaughter at two Australian abattoirs.
This study aimed to determine the presence and concentration of Escherichia coli O157 and Salmonella spp. on fleece, faeces and carcases of sheep during slaughter. Faeces, fleece and pre-chill carcase samples were collected from 164 sheep slaughtered at two Australian abattoirs. The presence of E. coli O157 and Salmonella spp. were determined by use of automated immunomagnetic separation (AIMS) with enumeration by use of the 'most probable number' (MPN) method. Escherichia coli O157 was isolated from 5% of faeces, 3% of fleeces and 0.6% of pre-chill carcases. The mean log(10) count of E. coli O157 positive faecal samples was 2.32 MPN/g, but counts on fleeces and carcases were below the countable limit (-1 log(10) MPN/cm(2) ). Salmonella spp. were isolated from 20% of faeces, 13% of fleeces and 1.3% of pre-chill carcases. The mean log(10) count of Salmonella spp. in faeces was 1.43 MPN/g and on fleece was -0.24 MPN/cm(2) , but counts on carcases were below the countable limit (-1 log(10) MPN/cm(2) ). The prevalence and concentration of pathogens were low in the sheep tested in this study, indicating a low risk of human infection from products derived from these animals.


Effects of ultraviolet and blue-light filtering on sleep: a meta-analysis of controlled trials and studies on cataract patients.
Two types of intraocular lenses (IOLs), namely ultraviolet-filtering IOL (UVF-IOL) and blue-light-filtering IOL (BF-IOL), are used to replace the aging lens in cataract patients. This provides a clinical scenario to investigate the BF and UVF effects on circadian rhythm. We revisited this topic and conducted an updated meta-analysis investigating the effects of UVF-IOL and BF-IOL on sleep quality. A literature search was conducted using the PubMed, Embase, and Cochrane Library databases, and finally, four randomized controlled trials, one nonrandomized controlled study, and two cohort studies were included in this meta-analysis. The fixed-effect model revealed a significantly larger sleep quality improvement in the UVF-IOL group than in the BF-IOL group (standard mean difference [SMD] = 0.10, 95% confidence interval [CI]: 0.00-0.21) at 3-8 weeks but not 7-12 months after IOL implantation (SMD = 0.03, 95% CI: -0.08 to 0.13). The random effects model revealed no difference between groups at 3-8 weeks (SMD = 0.16, 95% CI: -0.07 to 0.39) and 7-12 months (SMD = 0.03, 95% CI: -0.08 to 0.13) after IOL implantation. Our study found some weak evidence supporting that UVF-IOL implantation demonstrated a greater improvement in subjective sleep quality than the BF-IOL implantation only in a shorter period but not in a longer period. More trials should be conducted before further recommendations. Nevertheless, our study provides some insights into the effects of short wavelength electromagnetic radiation on the circadian rhythm. PROSPERO registration number: CRD42019128832.


Colored Shade Nets Can Relieve Abnormal Fruit Softening and Premature Leaf Senescence of "Jumeigui" Grapes during Ripening under Greenhouse Conditions.
High temperature causes premature grape leaf senescence, abnormal berry softening, and shortening of the fruiting period. Furthermore, the fruit quality and yield are severely affected. Here, the "Jumeigui" grape quality and leaf senescence were evaluated under shading; green, blue, black, and gray nets were used for shading, and their spectra were measured. At the same density, the shade-net color significantly affected cooling and shading efficiencies, with gray nets showing the best light transmission and cooling effect. Shading significantly alleviated abnormal heat-induced grape softness. The total soluble solids (TSS) content and grape coloration were affected under gray, blue, and green shade nets. Nonetheless, TSS exceeded 18 °Brix under gray, blue, and green nets, as required of first-class high-quality fruit. The peel color was not significantly affected under gray or blue shade nets, whereas unshaded grapes showed clear heat-stress damage, especially on the edges of unshaded bottom leaves, in which the net photosynthesis rate was significantly lower than that under shading, indicating that high light intensity and heat caused premature leaf senescence. Colored shade nets reduced greenhouse temperature and light intensity, thereby alleviating the premature senescence of grape plants. Grape quality under black shade nets was poor, whereas superior quality was achieved using gray or blue shade nets.


Parenting, self-regulation, and treatment adherence in pediatric chronic headache: A self-determination theory perspective.
This study examined parenting factors associated with children's self-regulation and physician-rated treatment adherence using a self-determination theory framework in pediatric chronic headache. Participants were 58 children and adolescents (aged 10-17 years), who underwent initial and follow-up multidisciplinary evaluation at a headache clinic, and their mothers. Regression analyses showed that higher maternal autonomy support and structure were significantly related to children's lower treatment-related reactance and higher adherence. Maternal controllingness had associations in the opposite directions. Children's fear of pain was related to maternal controllingness. Results suggest the importance of parents' provision of clear expectations and engaging children in treatment problem-solving and decision-making.


Halo dermatitis around a melanocytic naevus: Meyerson's naevus.
A case of halo dermatitis (eczema) around a pigmented naevus is reported. This appears to be a not uncommon condition which is not described in major dermatology textbooks. The relevant literature is reviewed, and the eponym 'Meyerson's naevus' is suggested.


Half-calcified calmodulin promotes basal activity and inactivation of the L-type calcium channel CaV1.2.
The L-type Ca2+ channel CaV1.2 controls gene expression, cardiac contraction, and neuronal activity. Calmodulin (CaM) governs CaV1.2 open probability (Po) and Ca2+-dependent inactivation (CDI) but the mechanisms remain unclear. Here, we present electrophysiological data that identify a half Ca2+-saturated CaM species (Ca2/CaM) with Ca2+ bound solely at the third and fourth EF-hands (EF3 and EF4) under resting Ca2+ concentrations (50-100 nM) that constitutively preassociates with CaV1.2 to promote Po and CDI. We also present an NMR structure of a complex between the CaV1.2 IQ motif (residues 1644-1665) and Ca2/CaM12', a calmodulin mutant in which Ca2+ binding to EF1 and EF2 is completely disabled. We found that the CaM12' N-lobe does not interact with the IQ motif. The CaM12' C-lobe bound two Ca2+ ions and formed close contacts with IQ residues I1654 and Y1657. I1654A and Y1657D mutations impaired CaM binding, CDI, and Po, as did disabling Ca2+ binding to EF3 and EF4 in the CaM34 mutant when compared to WT CaM. Accordingly, a previously unappreciated Ca2/CaM species promotes CaV1.2 Po and CDI, identifying Ca2/CaM as an important mediator of Ca signaling.


Daily feeding regimen impacts pig growth and behavior.
A primary swine production goal is to increase efficiency of lean tissue gains. While many swine production systems currently utilize ad libitum feeding, recent research suggests that altering feeding patterns may impact feed efficiency. Therefore, the objective of this study was to compare two feeding patterns and evaluate their impact on whole body tissue accretion, feeding behavior and activity in growing pigs. Forty eight individually housed gilts (55.9±5.2kg on test BW) were assigned into one of two feeding treatments: 1) Free access to the feeder (Free Access) or 2) twice daily access where gilts were allowed to eat ad libitum between 08:00-09:00h and again from 17:00-18:00h (2×). Pig performance was recorded weekly for 55days and average daily gain (ADG), average daily feed intake (ADFI), and gain:feed (G:F) was calculated. Body composition was assessed in 12 gilts per treatment using dual X-ray absorptiometry (DXA) at day -3 and 55 of treatment, and tissue accretion rates were calculated. Gilt behaviors were assessed via video analysis during week 7 and included time spent eating, feeding rate, enrichment interaction, postural changes, standing, sitting, and lying behaviors. Gilts fed 2× had lower ADG and ADFI compared to Free Access gilts (P≤0.01); however, no treatment difference in G:F was observed (P=0.83). At day 55 gilts fed 2× had a lower fat:protein compared to Free Access gilts (P=0.05). Fat, lean, and protein accretion rates were lower in gilts fed 2× compared to those fed Free Access (P=0.01). Gilts fed 2× ate less frequently and for a shorter duration of time, interacted with enrichment more frequently (P≤0.005), and tended to have less frequent postural changes compared to Free Access gilts (P=0.08). No treatment differences were observed in duration of time spent standing, sitting, or lying (P≥0.39). Although feed regimen did not alter feed efficiency, these data indicate that twice daily feeding reduced gilt adiposity and growth without altering the pig's behavioral expression of hunger. Therefore, twice daily feeding may be a method of increasing percent of lean tissue without negatively impacting gilt welfare.


Characteristics and stability of hallucinations and delusions in patients with borderline personality disorder.
Psychotic features have been part of the description of the borderline personality disorder (BPD) ever since the concept "borderline" was introduced. However, there is still much to learn about the presence and characteristics of delusions and about the stability of both hallucinations and delusions in patients with BPD. A follow-up study was conducted in 326 BPD outpatients (median time between baseline and follow-up = 3.16 years). Data were collected via telephone (n = 267) and face-to-face interviews (n = 60) including the Comprehensive Assessment of Symptoms and History interview, Positive And Negative Syndrome Scale and the Psychotic Symptom Rating Scale. The point prevalence of delusions was 26%, with a median strong delusion conviction. For the group as a whole, the presence and severity of both hallucinations and delusions was found to be stable at follow-up. Participants with persistent hallucinations experienced more comorbid psychiatric disorders, and they differed from those with intermittent or sporadic hallucinations with their hallucinations being characterized by a higher frequency, causing a higher intensity of distress and more disruption in daytime or social activities. Delusions in patients with BPD occur frequently and cause distress. Contrary to tenacious beliefs, hallucinations and delusions in participants with BPD are often present in an intermittent or persistent pattern. Persistent hallucinations can be severe, causing disruption of life. Overall, we advise to refrain from terms such as "pseudo", or assume transience when encountering psychotic phenomena in patients with BPD, but rather to carefully assess these experiences and initiate a tailor-made treatment plan.


Sonographic appearance of fallopian tube carcinoma.
Fallopian tube carcinoma is the least common of gynecological malignancies. We report the case of a 56-year-old woman who presented with a 2 1/2-year history of intermittent vaginal bleeding and lower abdominal pain. Transvaginal sonography revealed a cystic lesion of the fallopian tube with papillary projections, distinct from the ovary and uterus. Doppler examination showed low vascular impedance (resistance index 0.50, pulsatility index 0.80). The suspicion of tubal malignancy was confirmed at surgery.


Double emulsions as a high-throughput enrichment and isolation platform for slower-growing microbes.
Our understanding of in situ microbial physiology is primarily based on physiological characterization of fast-growing and readily-isolatable microbes. Microbial enrichments to obtain novel isolates with slower growth rates or physiologies adapted to low nutrient environments are plagued by intrinsic biases for fastest-growing species when using standard laboratory isolation protocols. New cultivation tools to minimize these biases and enrich for less well-studied taxa are needed. In this study, we developed a high-throughput bacterial enrichment platform based on single cell encapsulation and growth within double emulsions (GrowMiDE). We showed that GrowMiDE can cultivate many different microorganisms and enrich for underrepresented taxa that are never observed in traditional batch enrichments. For example, preventing dominance of the enrichment by fast-growing microbes due to nutrient privatization within the double emulsion droplets allowed cultivation of slower-growing Negativicutes and Methanobacteria from stool samples in rich media enrichment cultures. In competition experiments between growth rate and growth yield specialist strains, GrowMiDE enrichments prevented competition for shared nutrient pools and enriched for slower-growing but more efficient strains. Finally, we demonstrated the compatibility of GrowMiDE with commercial fluorescence-activated cell sorting (FACS) to obtain isolates from GrowMiDE enrichments. Together, GrowMiDE + DE-FACS is a promising new high-throughput enrichment platform that can be easily applied to diverse microbial enrichments or screens.


Assessment of coronary artery abnormalities and variability of Z-score calculation in the acute episode of Kawasaki disease-A retrospective study from China.
Accurate classification of coronary artery abnormalities (CAAs) is essential for clinical decision-making and long-term management in Kawasaki disease (KD) patients. To date, there are several echocardiographic criteria of CAA assessment. The Japanese Ministry of Health (JMH) criteria and the Z-score criteria from 2004 American Heart Association guidelines were adopted and their detective efficacies for CAAs were compared in 251 Chinese patients with KD Z scores were calculated by 6 published methods. According to the JMH criteria, 19 (7.57%) KD patients were classified as CAAs during the acute KD episode. However, the detective number of CAAs was highest and had a 0.68-fold increase by the Dallaire et al method with a Z-score cut point of ≥2.5 as compared with the JMH criteria; in contrast, more than 78.95% of patients with CAAs identified by the JMH criteria had a coronary artery Z score ≥2.5. All 6 different Z-score methods had satisfactory accuracies with a range from 93.23% to 97.61% in screening CAAs. For the 19 patients with CAAs identified by the JMH criteria, their Z scores presented the widest variation calculated by the McCrindle et al method. The JMH criteria underestimate the prevalence of CAAs as compared with the Z-score criteria. Quantitative assessment of coronary artery luminal dimensions, normalized as Z scores adjusted for body surface, should be recommended. The larger coronary artery luminal dimensions vary, the more heterogeneous Z scores calculated by different methods have.


Comparative Effectiveness of Ranolazine Versus Traditional Therapies in Chronic Stable Angina Pectoris and Concomitant Diabetes Mellitus and Impact on Health Care Resource Utilization and Cardiac Interventions.
Comparative studies evaluating traditional versus newer antianginal (AA) medications in chronic stable angina pectoris (CSA) on cardiovascular (CV) outcomes and utilization are limited, particularly in patients with diabetes mellitus (DM). Claims data (2008 to 2012) were analyzed using a commercial database. Patients with CSA receiving a β blocker (BB), calcium channel blocker (CCB), long-acting nitrate (LAN), or ranolazine were identified and followed for 12 months after a change in AA therapy. Patients on traditional AA medications were required to have concurrent sublingual nitroglycerin. Therapy change was defined as adding or switching to another traditional AA medication or ranolazine to identify patients whose angina was inadequately controlled with previous therapy. Four groups were identified (BB, CCB, LAN, or ranolazine users) and matched on relevant characteristics. A DM subset was identified. Logistic regression compared revascularization at 30, 60, 90, 180, and 360 days. Negative binomial regression compared all-cause, CV-, and DM-related (in the DM cohort) health care utilization. A total of 8,008 patients were identified with 2,002 patients in each matched group. Majority were men (mean age 66 years). A subset of 3,724 patients with DM (BB, n = 933; CCB, n = 940; LAN, n = 937; and ranolazine, n = 914) resulted from this cohort. Compared to ranolazine in the overall cohort, traditional AA medication exhibited greater odds for revascularization and higher rates in all-cause outpatient, emergency room visits, inpatient length of stay, and CV-related emergency room visits. In the DM cohort, ranolazine demonstrated similar benefits over traditional AA medication. In conclusion, ranolazine use in patients with inadequately controlled chronic angina is associated with less revascularization and all-cause and CV-related health care utilization compared to traditional AA medication.


Prioritization of therapeutic targets of inflammation using proteomics, bioinformatics, and in silico cell-cell interactomics.
Leukocyte extravasation is a multistep process, involving the movement of leukocytes out of the circulatory system, through vascular endothelium and to the site of tissue damage or infection. Protein-protein interactions play key roles in the extravasation process and have been attractive therapeutic targets for inhibiting inflammation using blocking (or neutralizing) antibodies. These targets include protein-protein interactions between cytokines (or chemokines) and their receptors on leukocytes and between adhesions molecules involving leukocyte-endothelium contacts. A number of therapeutics against these targets are currently used in clinic for treatment of inflammatory disorders, however, they are associated with side-effects partly due to the off-target actions (i.e., nonspecific targets). There is a need for novel targets involved in the leukocyte extravasation process that are specific to leukocyte subsets or to individual inflammatory disorder, and are amenable for drug development (i.e., duggable). In this chapter, we describe a methodology to identify novel "druggable" targets involving protein-protein interactions between activated leukocytes and endothelial cells using a combination of proteomics, bioinformatics and in silico interactomics. The result is a prioritized list of protein-protein interactions in a network consisting of leukocyte-endothelial cell communication and contacts. These prioritized targets can be pursued for the development of therapeutics such as neutralizing antibodies and for their validation through preclinical testing. The method described here provides the workflow to identify and clinically target important cell-cell interactions that are specific/selective for particular inflammatory disorders and to improve currently available therapies.


Scoring model to predict risk of chronic kidney disease in Chinese health screening examinees with type 2 diabetes.
As health screening continues to increase in China, there is an opportunity to integrate a large number of demographic as well as subjective and objective clinical data into risk prediction modeling. The aim of this study was to develop and validate a prediction model for chronic kidney disease (CKD) in Chinese health screening examinees with type 2 diabetes mellitus (T2DM). We conducted a retrospective cohort study consisting of 2051 Chinese T2DM patients between 35 and 78 years old who were enrolled in the XY3CKD Follow-up Program between 2009 and 2010. All participants were randomly assigned into a derivation set or a validation set at a 2:1 ratio. Cox proportional hazards regression model was selected for the analysis of risk factors for the development of the proposed risk model of CKD. We established a prediction model with a scoring system following the steps proposed by the Framingham Heart Study. The mean follow-up was 8.52 years, with a total of 315 (23.20%) and 189 (27.27%) incident CKD cases in the derivation set and validation set, respectively. We identified the following risk factors: age, gender, body mass index, duration of type 2 diabetes, variation of fasting blood glucose, stroke, and hypertension. The points were summed to obtain individual scores (from 0 to 15). The areas under the curve of 3-, 5- and 10-year CKD risks were 0.843, 0.799 and 0.780 in the derivation set and 0.871, 0.803 and 0.785 in the validation set, respectively. The proposed scoring system is a promising tool for further application of assisting Chinese medical staff for early prevention of T2DM complications among health screening examinees.


Recurrent urinary tract infections led to the diagnosis of cross-renal ectopia: A case report.
Crossed renal ectopy (CRE) is a very rare congenital kidney anomaly. CRE is usually asymptomatic and is most often discovered incidentally, but the patient may sometimes develop various renal manifestations. We report a case of a girl who was symptomatic of several episodes of urinary tract infections and whose investigations including ultrasound, uroscan, renal scan and voiding cystourethrogram concluded that she had a crossed left renal ectopy without vesico-ureteral reflux. A regular Follow-up revealed no further symptoms or complications, with partial resolution of the hydronephrosis, and no recurrence of urinary tract infections after hygienic rules. This case didn't require surgical intervention. CRE is an infrequently occurring congenital malformation. Uroscan is an excellent tool to describe the full anatomical details of this pathology; and the information provided is crucial for surgeons, nephrologists, and radiologists to aid in the proper handling of this pathology. CRE is a rare disease that can be diagnosed incidentally. Treatment is only indicated if complications occur or if there is other associated renal disease. Patients require continuous follow-up and need to be examined for potential complications.


Recent advances in bacteriophage therapy: how delivery routes, formulation, concentration and timing influence the success of phage therapy.
Bacteriophages are bacteria-specific viruses that infect and, in the case of obligately lytic phages, destroy their host bacteria. Phage therapy has been used therapeutically to combat bacterial infections since their discovery. This paper reviewed recent in-vivo phage therapy studies, with a distinct focus on the effect of delivery routes, phage concentration and timing of administration on the success of the therapy. It was found that the most successful route of administration for the treatment of systemic infections was via the parenteral route. Oral delivery is mainly used to treat gastrointestinal infections. However, in some cases phages can also reach the systemic circulation. Local delivery (skin, ears, teeth) has proved extremely successful in the treatment of topical infections, as has the inhalation of phages for the treatment of lung infections. The ability of phages to prevent biofilm formation on medical devices has received much attention, mainly in the area of catheter coatings. This review also highlights areas in which phage therapy needs substantial development. Many papers were lacking in formulation details, with crude phage stocks being used in most cases. No phage stability data were included in any of the papers. The review concluded that although phage therapy is an excellent alternative for the treatment of bacterial infections, optimisation of formulations and long-term stability data is required before it can be widely used within a clinical setting.


Synergistic effect of combined imipenem and photodynamic treatment with the cationic Ir(III) complexes to polypyridine ligand on carbapenem-resistant Klebsiella pneumoniae.
Carbapenemase-producing strains of Klebsiella pneumoniae (KPC+) are one of the multi-drug resistant bacteria with the highest risk for human health. The colistin is the only antibiotic option against KPC+; however, due to its emerging resistance, therapies such as antimicrobial photodynamic inactivation (aPDI), are needed. APDI uses photosensitizer compounds (PS) to produce light-activated local oxidative stress (photooxidative stress). Within the PSs variety, cationic PSs are thought to interact closely with the bacterial envelope producing an increased cytotoxic effect. The Ir(III)-based cationic compounds, PSIR-3, and PSIR-4 were tested on aPDI and compared to a positive control of Ru(II)-based PS. The PSIR-3 and PSIR-4 abilities to inhibit the growth of KPC+ and KPC- bacteria were evaluated, under 17 μW/cm2 photon flux. Also, the cytotoxicity of the PSs in eukaryotic cells was determined by MTS and trypan blue exclusion assays. After light-activation, only the PSIR-3 compound inhibited 3 log10 (> 99.9 %) bacterial growth in a minimum dose of 4 μg/mL with the lethality of 30 min of light exposure. Outstandingly, the compound PSIR-3 showed a synergistic effect with imipenem, significantly increasing the bacterial inhibition of KPC+ to 6 log10, which was not observed in the control compound. In normal immortalized gastric cell line GES-1, the compound PSIR-3 showed no significant cytotoxicity, although increased cytotoxicity under light-activation was observed on gastric cancer-derived cells AGS. The PSIR-3 compound produces an efficient aPDI, killing K. pneumoniae KPC+- strains, and increasing its susceptibility in conjunction with imipenem, exhibiting low cytotoxicity to normal eukaryotic cells.


Sagittal sinus thrombosis in a patient with familial Protein C deficiency: Highlighting the impact of thrombophilia testing.
Plasma protein-C is a natural anticoagulant that inactivates factors Va and VIIIa. Familial protein C deficiency is inherited as an autosomal dominant disorder. The homozygous or compound heterozygous type may present early as purpura fulminant, while the heterozygous type can present as thromboembolism later in life. Presented in this report is a case of a 21-year-old female patient with protein-C deficiency, confirmed by thrombophilia investigations. She experienced recurrent deep vein thrombosis and cerebral sinus thrombosis due to thrombotic occlusion. She had a family history of deep vein thrombosis. Hence, high-risk cases should be seriously considered for long term anticoagulation therapy. The utility versus futility of thrombophilia testing in a particular situation is discussed to address and ensure safe practice among patients with thromboembolism.


Biological treatment of mining wastewaters by fixed-bed bioreactors at high organic loading.
Acid wastewaters contaminated with Fe - 1000 mg L(-1) and Cu - 100 mg L(-1) were remediated by microbial sulfate-reduction at high organic loading (theoretical TOC/SO4(2-) ratio 1.1) in a laboratory installation. The installation design includes a fixed-bed anaerobic bioreactor for sulfate-reduction, a chemical reactor, a settler and a three-sectional bioreactor for residual organic compounds and hydrogen sulfide removal. Sulfate-reducing bacteria are immobilized on saturated zeolite in the fixed-bed bioreactor. The source of carbon and energy for bacteria was concentrated solution, containing ethanol, glycerol, lactate and citrate. Heavy metals removal was achieved by produced H2S at sulfate loading rate 88 mg L(-1)h(-1). The effluent of the anaerobic bioreactor was characterized with high concentrations of acetate and ethanol. The design of the second bioreactor (presence of two aerobic and an anoxic zones) makes possible the occurrence of nitrification and denitrification as well as the efficiently removal of residual organic compounds and H2S.


Identification of sulforhodamine B photodegradation products present in nonpermanent tattoos by micro liquid chromatography coupled with tandem high-resolution mass spectrometry.
This article deals with the photodegradation of sulforhodamine B, a dye widely used in nonpermanent tattoos. Degradation evidence was obtained from both aqueous and sweat-simulating solutions of the dye after 9 days of Solarbox irradiation. The identification of the degradation products was achieved using a nontarget approach. For this purpose, a micro liquid chromatography method coupled with tandem high-resolution mass spectrometry was developed. In addition, the chemical structures of five degradation products and two dye impurities were elucidated. The degradation products were the same for both types of solution, whereas the degradation rate of the dye in sweat-simulating solution was slightly faster than that in aqueous solution. The method was also applied to samples of tattooed pigskin subjected to irradiation, in order to better simulate the irradiation effects on the dye used on the skin. None of the degradation products found in the sulforhodamine B solutions were identified in the degraded tattooed pigskin samples, but a new signal at m/z 637.3051 (positive ionization) was found, and the structure of the corresponding molecule was elucidated. The mutagenicity of the photodegradation products was evaluated using a quantitative structure-activity relationship approach, which gave negative results for all the structures elucidated. Graphical Abstract Comparison between tattoed pigskin before and after photodegration process. Strategies for the identification of sulforhodamine B degradation products.