The 5-HT7 receptor triggers cerebellar long-term synaptic depression via PKC-MAPK.
The 5-HT7 receptor (5-HT7R) mediates important physiological effects of serotonin, such as memory and emotion, and is emerging as a therapeutic target for the treatment of cognitive disorders and depression. Although previous studies have revealed an expression of 5-HT7R in cerebellum, particularly at Purkinje cells, its functional role and signaling mechanisms have never been described. Using patch-clamp recordings in cerebellar slices of adult mice, we investigated the effects of a selective 5-HT7R agonist, LP-211, on the main plastic site of the cerebellar cortex, the parallel fiber-Purkinje cell synapse. Here we show that 5-HT7R activation induces long-term depression of parallel fiber-Purkinje cell synapse via a postsynaptic mechanism that involves the PKC-MAPK signaling pathway. Moreover, a 5-HT7R antagonist abolished the expression of PF-LTD, produced by pairing parallel fiber stimulation with Purkinje cell depolarization; whereas, application of a 5-HT7R agonist impaired LTP induced by 1 Hz parallel fiber stimulation. Our results indicate for the first time that 5-HT7R exerts a fine regulation of cerebellar bidirectional synaptic plasticity that might be involved in cognitive processes and neuropsychiatric disorders involving the cerebellum.


Defective Ca++ handling and insulin release in islets of diabetic hamsters and mice.
In islets from normal Chinese hamsters preloaded with 45Ca, glucose-induced biphasic insulin release was accompanied by increased 45Ca++ efflux. Islets from diabetic hamsters showed decreased insulin release and no rise in 45Ca++ efflux. No rise in 45Ca++ efflux was seen, even when insulin release was potentiated by 3-isobutyl-1-methylxanthine (IBMX). Since glucose-induced 45Ca++ uptake was normal in diabetic hamsters a defect in cellular Ca++ handling may be involved in the defective insulin release. A similar decrease of glucose-induced insulin release in islets from diabetic C57BL/KsJ-db/db mice was, on the other hand, associated with a small increase in 45Ca++ efflux. In these islets, IBMX potentiated both insulin release and 45Ca++ efflux suggesting that the release defect may be restricted to glucose.


Pressure under the forefoot in rheumatoid arthritis. A comparison of static and dynamic methods of assessment.
The generation and transmission of forces under the foot was investigated in 67 normal subjects and 124 patients with rheumatoid arthritis. The investigations included the measurement of static foot-ground pressure patterns with a Pedobarograph and the assessment of transmission of maximum load during the gait cycle with instrumented force sandals. Information from both sources was compared with the patient's own subjective assessment of pain and walking ability. Static pressures accurately reflect the position of abnormal pressure generation.


Topical Sunitinib ointment alleviates Psoriasis-like inflammation by inhibiting the proliferation and apoptosis of keratinocytes.
Psoriasis is a chronic auto-immune inflammation disease with skin lesions and abnormal keratinocyte proliferation. Sunitinib, a multi-targeted tyrosine kinase inhibitor, is known to selectively inhibit several growth factor receptors, including vascular endothelial growth factor receptor, platelet-derived growth factor receptor and stem cell factor. It was reported that a patient with renal cell carcinoma (RCC) whose psoriatic lesion was resolved dramatically during treatment with Sunitinib, however, the mechanism is still unclear. We applied Sunitinib ointment to treat imiquimod-induced mouse model of psoriasis and found that Sunitinib ointment could alleviate imiquimod-induced psoriasis-like inflammation and reduce the Ki67 expression, while Sunitinib ointment couldn't reduce imiquimod-induced splenomegaly of the mouse model, then we concentrated on studying the effect of Sunitinib on the proliferation and apoptosis of keratinocytes, we cultivated HaCaT cells with epidermal growth factor (HaCaT/E cells) to represent as a state of highly proliferative psoriatic keratinocytes. We found that Sunitinib could inhibit the proliferation of Hacat/E cell in a time and concentration dependent manner by influencing the expression level of cell cycle protein D1, cycle protein E1, in addition, Sunitinib could induce the apoptosis of Hacat/E cell and up-regulate the expression of poly ADP-ribose polymerase (PARP). Sunitinib down-regulated the expression of phosphorylated signal transduction and activator of transcription 3 (p-Stat3) of Hacat/E cells significantly. We conclude that Sunitinib alleviates imiquimod-induced psoriasis-like inflammation by regulating the proliferation and apoptosis of HaCaT cells through inhibiting the expression of p-Stat3.


Validation of low-volume sampling devices for pharmacokinetic analysis: technical and logistical challenges and solutions.
While low-volume sampling technologies offer numerous advantages over venipuncture, implementation in clinical trials poses technical and logistical challenges. Bioanalytical methods were validated for measuring the concentration of crenezumab and etrolizumab in dried blood samples collected using Mitra and Tasso-M20. The data generated demonstrate that the concentrations of crenezumab and etrolizumab in dried blood collected by either device could be determined using calibrators prepared in serum. Drug concentrations from dried blood were converted to serum concentrations using patient hematocrit levels. Contract Research Organization experience in sample handling and analysis allowed us to compare differences between various low-volume sampling technologies. This study evaluated challenges and presented potential solutions for use of different low-volume sampling technologies for pharmacokinetic analysis.


Computerized and clinician assessment of depression and anxiety: respondent evaluation and satisfaction.
This investigation examined differences in subjects' satisfaction and reaction to computer- and clinician-administered versions of the Hamilton Depression and Anxiety Rating Scales in outpatients with affective disorders (n = 121), anxiety disorders (n = 52), other psychiatric disorders (n = 7), and adults without psychiatric disorders (n = 76). Subjects' reactions to clinician- and computer-administered interviews were similar in the areas of overall comfort level and ease in answering questions. Clinicians were rated more positively with regard to determining how subjects really felt, sensitivity to their needs, and asking questions specific to their feelings. Subjects felt less embarrassed giving information to the computer. We found psychiatric subjects to prefer the clinician-administered interview, whereas nonpsychiatric subjects indicated no preference.


[Thalassemia minor: case report].
We have presented a 21-year-old patient with microcytosis, iron level reaching the upper normal limit and with increased transferin saturation by this element. On the basis of the performed tests we have diagnosed thalassemia minor.


Predictors of Successful Laser Capsulotomy for Significant Posterior Capsule Opacification after Phacoemulsification.
This study aimed to determine the reasons behind the failure of laser capsulotomy (LC) performed for significant posterior capsular opacification (PCO). Eighty-eight eyes of 88 patients referred for LC at a tertiary care center were retrospectively analyzed. The data recorded included the cause of cataract, visual acuity, duration of PCO, location of PCO, intraocular lens (IOL) position, IOL type, and lens capsule status. These data were later analyzed for determining the requirement of high pulse energy during LC and the success rate of primary LC. The mean age of the participants was 55.77 ± 18.60 years with 58 (65.9%) male patients. The mean duration between cataract and LC surgeries was 45.58 ± 37.33 months. Senile (n=58), uveitic (n=12), post-pars plana vitrectomy (PPV) (n=12), and traumatic (n=6) cataracts were the common causes. Late-presenting PCO, trauma, uveitis, sulcus placement of IOLs, irregular capsulorhexis shape, and polymethyl methacrylate (PMMA) IOLs were significantly associated with unsuccessful LC and/or higher pulse energy settings during LC. Significant PCO is often associated with cataract caused by uveitis or trauma, and after PPV. PCO associated with trauma, sulcus placement of IOLs, and PMMA IOLs may need multiple LCs.


Hard Metal Lung Disease with Favorable Response to Corticosteroid Treatment: A Case Report and Literature Review.
Hard metal lung disease (HMLD) is a pneumoconiosis caused by occupational exposure to hard metals such as tungsten carbide and cobalt, but the treatment strategies for HMLD have not been well established. A 68-year-old Japanese man with occupational history as a grinder of hard metals for 18 years referred to our hospital because of dry cough and dyspnea. A chest computed tomography (CT) on admission revealed centrilobular micronodules, ground-glass opacities, and reticular opacities in the peripheral zone of both lungs. Mineralogic analyses of lung tissues detected components of hard metals, such as tungsten, titanium and iron, and the same metals were also detected in the sample of the dust of his workplace. Thus, the patient was diagnosed as having HMLD based on occupational exposure history and radiologic and mineralogic analyses of the lung. Corticosteroid therapy was initiated, which resulted in partial improvements in his symptoms, radiological and pulmonary functional findings. In a review of the 18 case reports of HMLD treated with corticosteroids, including our case, the majority of patients (77.8%) showed favorable responses to corticosteroid treatment. Furthermore, the presence of fibrotic changes, such as reticular opacity, in radiological examinations was associated with the resistance to corticosteroids. In conclusion, the majority of patients with HMLD are expected to favorable response to corticosteroid treatment, whereas chest CT findings such as fibrotic changes may be predictive of the resistance of corticosteroid treatment. Lastly, proper prevention of hard metal exposure is most important as the first step.


A professional knowledge base for collaborative reflection education: a qualitative description of teacher goals and strategies.
For several decades, educational experts have promoted reflection as essential to professional development. In the medical setting, collaborative reflection has gained significant importance across the curriculum. Collaborative reflection has a unique edge over individual reflection, but many medical teachers find facilitating group reflection sessions challenging and there is little documentation about the didactics of teaching in such collaborative reflection settings. To address this knowledge gap, we aim to capture the professional knowledge base for facilitating collaborative reflection by analyzing the formal and perceived goals and strategies of this practice. The professional knowledge base consists of formal curricular materials as well as individual teacher expertise. Using Template Analysis, we analyzed the goals and strategies of collaborative reflection reported in institutional training documents and video-stimulated interviews with individual teachers across all Dutch general practitioner training institutes. The analysis resulted in a highly diverse overview of educational goals for residents during the sessions, teacher goals that contribute to those educational goals, and a myriad of situation-specific teacher strategies to accomplish both types of goals. Teachers reported that the main educational goal was for residents to learn and develop and that the teachers' main goal was to facilitate learning and development by ensuring everyone's participation in reflection. Key teacher strategies to that end were to manage participation, to ensure a safe learning environment, and to create conditions for learning. The variety of strategies and goals that constitute the professional knowledge base for facilitating collaborative reflection in postgraduate medical education shows how diverse and situation-dependent such facilitation can be. Our analysis identifies a repertoire of tools that both novice and experienced teachers can use to develop their professional skill in facilitating collaborative reflection.


Early treatment with hydroxychloroquine prevents the development of endothelial dysfunction in a murine model of systemic lupus erythematosus.
Accelerated atherosclerosis is one of the major causes of morbidity in patients with systemic lupus erythematosus (SLE). Endothelial dysfunction (ED) is considered an early marker of atherosclerosis. It is a reversible alteration, thus representing an attractive target for prevention strategies against cardiovascular disease. Studies have shown that ED occurs in patients with SLE even in the absence of severe, active disease. Hydroxychloroquine (HCQ) is widely used in SLE to control disease activity, but its use is also associated with an improvement in long-term prognosis. Beyond the beneficial effect in well-established disease, our hypothesis is that treatment with HCQ might have a beneficial impact on ED prevention in SLE. The aim of this study was to assess the impact of early treatment with HCQ on ED in a murine model of SLE. Twelve-week-old NZB/W F1 (NZ) and C57BL/6 J mice (controls) were allocated to receive HCQ or vehicle for 6, 12, or 18 weeks. Proteinuria and anti-double-stranded DNA autoantibodies were determined. ED was assessed in mesenteric arteries (pressurized myography). Nitric oxide (NO) availability and reactive oxygen species (ROS) production were evaluated. Vascular ROS production was measured with dihydroethidium (DHE) fluorescent dye. Starting from 18 weeks of age, NZ mice showed a progressive reduction in NO availability, which was normalized by ascorbic acid and apocynin in the up to 24-week-old group, and partly ameliorated in older animals. HCQ administration normalized the NO availability in the up to 24-week-old group, with a partial amelioration in the 30-week-old group. DHE analysis revealed a progressive increment of vascular ROS generation among NZ groups, which was prevented by apocynin. Similarly, in the NZ HCQ-treated group, vascular ROS production was abrogated. The ED that characterizes this mouse model of SLE is caused by the nicotinamide adenine dinucleotide phosphate oxidase-driven ROS excess. Very early treatment with HCQ is able to exert vascular protection via an antioxidant effect.


Retraction.
The article "The circRNA-MYLK plays oncogenic roles in the Hep-2 cell line by sponging microRNA-145-5p" by Yao Chen, Yanmei Wang, Congcong Li, Xuechang Li, Tiejun Yuan, Shuqin Yang and Xiaoyan Sun, published in Gen. Physiol. Biophys. 39(3), 2020, pp. 229-237 (doi: 10.4149/gpb_2019060) has been retracted by agreement between the author(s) and journal's Editor in Chief, Prof. Dr. Lubica Lacinova, and AEPresss, s.r.o.. The corresponding author Xiaoyan Sun asked to retract this manuscript as there were some substantial problems in it, which needed more time and research to solve and can more fully re-examine and revise his research results.The authors were not available for a final confirmation of the retraction.


An eight-channel correlation electron cyclotron emission diagnostic for turbulent electron temperature fluctuation measurement in HL-2A tokamak.
A new correlation electron cyclotron emission (CECE) diagnostic has recently been installed on the HL-2A tokamak in order to study electron temperature fluctuations. Eight radial locations are measured simultaneously through eight pairs of correlated channels. Multiplexers are employed in the intermediate frequency section instead of the conventional separated filter banks to meet strict cross-isolation specifications and lower insertion loss. Relative electron temperature fluctuations are observed by CECE for the first time on the HL-2A by using the spectral decorrelation method. The achieved minimum detectable fluctuation level is up to (T̃e/Te)min∼0.5%. When studying electron temperature fluctuations in the core region with gas puffing, the cross-power spectra show that the amplitude of the electron temperature fluctuation increases in a high temperature and low density plasma. Further analysis demonstrates that the electron temperature gradient ∇Te drives the electron temperature fluctuations together with electron heat transport.


Complete regression of a congenital splenic cyst.
We report a congenital splenic cyst that was revealed by prenatal sonography at 31 weeks' gestation. Serial prenatal sonographic examinations showed a slight enlargement of the cyst. However, sonography performed when the infant was 7 months of age showed the cyst had spontaneously and completely regressed. We recommend that practitioners adopt a more conservative approach in such infants, one that includes follow-up sonographic examinations, rather than instituting interventional treatment.


Processes for culturally adapting behavioral health interventions for people with refugee backgrounds: A scoping review.
Academic literature supports cultural adaptation (CA) of evidence-informed interventions to increase accessibility and effectiveness of behavioral health treatment to meet the needs of a culturally diverse society. While several meta-analyses have shown positive outcomes of CA mental health interventions, there is a need for more information about how theoretical CA models have been applied in practice to meet the cultural and contextual needs of specific groups. This scoping review was conducted to understand how CA models have been applied to adapt evidence-informed behavioral health interventions for people with refugee backgrounds in resettlement. Eighteen manuscripts were identified and analyzed, resulting in five categories: Reasons for Engaging in CA, Processes of CA, Types of CAs, Resources Needed to Support CA, and Evaluating Adaptation Choices. Only four studies utilized any existing model to guide their adaptation efforts, three of which used CA models. Level of detail regarding CA processes and justification for choices varied considerably among articles. Significant gaps were identified, posing challenges for replication. Although articles reported that adapted interventions were effective, it is unclear which, if any, CA choices contributed to the successful outcomes. Findings indicate a need for emphasis on clear and thorough documentation of CA processes and more rigorous assessment of the impact of adaptation choices.


[Conservative and surgical therapy of hip osteoarthritis].
Conservative measures generally have priority over surgical procedures. Firstly, an analgesic and antiphlogistic therapy during the acute pain phase is very effective. Secondly, retaining or improving mobility is important. The indication for surgery for hip arthritis exists when the clinical and subjective symptoms in conjunction with the radiological finding can no longer be adequately controlled by conservative measures. Surgical interventions are basically either joint-replacing or joint-saving. The goal of all corrective osteotomies is to improve the hip joint congruency and thus delay the replacement of the hip with an artificial joint. Established prosthetic models show long-term results of 15-20 years with a survival rate of more than 90%.


[Methylation analysis of CpG island DNA of FMR1 gene in the fragile X syndrome].
To establish a method of methylation-sensitive restriction enzymes based quantitative PCR (MSRE-qPCR) for analysis of CpG island DNA of FMR1 gene, and to assess its value for molecular diagnosis of fragile X syndrome. Thirty boys with mental retardation and abnormal repeats of 5'(CGG)n in the FMR1 gene and 20 mothers were analyzed by conventional PCR screening. Eag I was used to digest genomic DNA, and qPCR was performed to amplify CpG island in the FMR1 gene using both undigested and digested templates. Raw Ct values were obtained through quantitative PCR amplification. The degree of CpG island methylation was calculated by 2 - U+0394 U+0394 Ct. The result of MSRE-qPCR was verified by Southern blotting. 30 healthy females and 30 healthy males were used as controls to optimize the established MSRE-qPCR method. The ranges of 2 - U+0394 U+0394 Ct value for normal methylation, partial methylation and full methylation were determined. Among the 30 patients, 3 were found to have partial methylation of CpG island of the FMR1 gene, and 27 were found to have full methylation (3/30 results were verified by Southern blotting). Only 7 mothers were found abnormal methylation of CpG island of FMR1 gene, whilst the remaining 13 mothers were normal. MSRE-qPCR is a quick and reliable method for quantitative analysis of CpG island methylation status in FMR1 gene, which may provide a new strategy for the diagnosis of fragile X syndrome.


Fabrication of organic light-emitting devices comprising stacked light-emitting units by solution-based processes.
Multi-organic light-emitting devices comprising two light-emitting units stacked in series through a charge-generation layer are fabricated by solution processes. A zinc oxide nanoparticles/polyethylene-imine bilayer is used as the electron-injection layer and phosphomolybdic acid is used as the charge-generation layer. Appropriate choice of solvents during spin-coating of each layer ensures the nine-layered structure fabricated by solution processes.


Characterization of a cell mutant specifically defective in the synthesis of anticoagulantly active heparan sulfate.
We have investigated the characteristics of clonal L cell mutant VI-7 that has previously been demonstrated to exhibit reduced levels of cell surface proteoglycans containing heparan sulfate (HS) with regions of defined monosaccharide sequence that interact with antithrombin (HSact) (de Agostini, A. L., Lau, H. K., Leone, C., Youssoufian, H., and Rosenberg, R. D. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 9784-9788). Pulse labeling revealed that the synthesis of HSact in mutant cells, as compared to wild-type cells, was reduced by 5-7-fold, which is identical to the previously observed reduction in cell surface-bound antithrombin. This alteration is independent of growth state since production of HSact by mutant cells, as compared to wild-type cells, is decreased to a similar extent in exponentially growing and post-confluent cultures. The synthetic defect was specific for HSact since production of total HS and chondroitin sulfate by mutant cells, as compared to wild-type cells, was identical in magnitude. The synthetic abnormality is not due to an alteration in core protein since complementation was not observed when mutant cells were stably transfected with the epitope-tagged ryudocan cDNA which can initiate HSact production. Structural analyses revealed that HS from mutant cells, as compared to wild-type cells, exhibited normal molecular weight, extent and distribution of sulfate, and disaccharide composition, which indicate that the mutation did not affect HS biosynthetic enzymes. Together, the data suggest that mutant VI-7 is defective in a regulatory component which directly or indirectly coordinates HS biosynthetic enzymes to specifically generate the defined monosaccharide sequence of HSact.


FEEDING AND OXYGEN UPTAKE OF THE TROPICAL SEA URCHIN EUCIDARIS TRIBULOIDES (LAMARCK).
1. In the laboratory Eucidaris tribuloides showed a food preference for rock infested with the boring sponge Cliona lampa over turtle grass (Thalassia testudinum), several algae, and fish strips. 2. In the laboratory, urchins consumed wet rock infested with Cliona lampa at rates ranging from less than one to over three gm. per day depending on the size of the urchin. 3. Oxygen consumption of urchins was measured in the laboratory with a modified Scholander volumetric respirometer. 4. Oxygen uptake decreased significantly during the first day of starvation, but then remained relatively stable during several successive days of starvation. 5. There was not a significant correlation between gonad index or sex of the urchin and relative oxygen uptake. 6. Relative oxygen consumption decreased with increasing size of the urchin. Values for "b" indicated an oxygen uptake which was almost proportional to surface area at 20° and 30 ° C. 7. Oxygen uptake fluctuated during the first hour when urchins were placed in water several degrees colder than their ambient water. At the end of this hour, however, the rate of oxygen uptake had become relatively stable. Well-fed urchins manifested greater changes in their stabilized rates of oxygen uptake (Q10) at different temperatures than did starved urchins. 8. Urchins manifested partial seasonal acclimation of oxygen uptake as indicated by the fact that winter oxygen consumption curves were well above summer curves at the corresponding temperatures. The acclimation was probably not complete since mean summer oxygen uptake was higher at the summer ambient than the mean winter oxygen uptake at the winter ambient.


Assessment of a computational strategy approaching spectroscopic accuracy for structure, magnetic properties and vibrational frequencies of organic free radicals: the F(2)CN and F(2)BO case.
The molecular structure, vibrational frequencies, and hyperfine couplings of F(2)CN and F(2)BO have been computed at the coupled cluster level in conjunction with hierarchical series of correlation consistent basis sets. For geometrical and hyperfine parameters, extrapolation to the complete basis set limit and inclusion of core correlation effects have been considered. While a remarkable agreement with most of vibrational frequencies supports the reliability of the computational approach followed, experimental geometries cannot be used for validation purposes due to their limited accuracy. In view of previous experience with related radicals, the computed hyperfine coupling constants as well as molecular structures are expected to be very reliable and accurate.


Anatomical Study of the Caudate Lobe with Special Reference to Portal Venous and Biliary Branches Using Corrosion Liver Casts and Clinical Application.
The definition and extent of the human caudate lobe in the liver is unclear, and thus, the anatomy of the caudate lobe was studied using 23 corrosion liver casts, with special reference to the portal venous and biliary branches. These branches and their ramification type in the caudate lobe showed that this lobe includes: (1) the Spiegel lobe; (2) the paracaval portion; and (3) the caudate process portion. The three portions often have their own independent branches; for example, the portal venous and biliary branches of the Spiegel lobe were ramified mainly from the left-side tract, whereas those of the caudate process portion were ramified from the right-side tract. The portal venous branches of the paracaval portion were ramified mainly from the left portal vein, while the biliary branches of this portion drained into the right and left biliary tracts at almost equal frequencies. In most cases, the peripheral branches reached the liver surface beneath the diaphragm. Thus, the present division of the caudate lobe into three portions could make the extent of the caudate lobe clear and is considered logical from a clinical viewpoint.


Controlled radiofrequency endovenous occlusion using a unique radiofrequency catheter under duplex guidance to eliminate saphenous varicose vein reflux: a 2-year follow-up.
Saphenous vein reflux is often the underlying anatomic cause of varicose veins. It is necessary to eliminate this reflux originating at the saphenofemoral junction (SFJ) to treat the resultant varicose veins. To report 2-year follow-up results after closing the incompetent greater saphenous vein starting from its junction (SFJ) with the femoral vein using radiofrequency (RF) endoluminal ablation. One hundred and forty incompetent greater saphenous veins from 120 patients with an incompetent SFJ and large painful varicosities were treated. Patients were evaluated clinically and with duplex ultrasound at 1 week, 6 weeks, 6 months, 12 months, and 24 months to determine treatment efficacy as well as adverse sequelae. Vein occlusion, defined as the absence of any duplex ultrasound-determined flow, was successfully achieved in 137 of 140 (98%) scanned veins at 1-week follow-up. At the 12-month follow-up, none of the treated patients developed recanalization that was not seen at 6 weeks, with a successful outcome in 90%. At the 24 month follow-up, 19 of 21 patients had complete disappearance of the treated saphenous vein, for a success rate of 90%. Side effects were minimal, and no skin burns or thromboses were observed. RF endovenous occlusion allows patients to obtain treatment with the positive attributes of surgery, that is, a single treatment and low rate of recurrent reflux, but without the morbidity, need for general anesthesia, or extensive convalescence associated with vein stripping and ligation surgery. Patient satisfaction was routinely achieved, with 98% of patients indicating a willingness to recommend the RF endovascular procedure to a friend or family member.


Analyzing the disparities in the coverage of maternal and child health services: A district-level cross-sectional analysis of Jammu and Kashmir.
Improving overall coverage of maternal and child health (MCH) services is essentially required if India in general and Jammu and Kashmir state in particular have to attain the Sustainable Development Goals by the year 2030. Thus, the disparities in coverage of MCH services need to be assessed and addressed. The objective of this study was to examine the variation in coverage rates for a key set of interventions in MCH services and to assess the relationship between coverage gap and socioeconomic development across the districts of Jammu and Kashmir. Data from the National Family Health Survey-4 (NFHS-4), 2015-2016, Census of India 2011, and Digest of Statistics Jammu and Kashmir were used to construct two composite indexes of coverage gap and socioeconomic development at district level. Cronbach's alpha was used to assess the internal consistency of indicators used in the two indexes. The overall coverage gap in the state was 28.17%, and the size of coverage gap was largest for family planning interventions (55.8%), followed by treatment of sick children (26.95%) and maternal and newborn care (18.75%), and was smallest for immunization (10.5%). There is a moderate negative correlation between coverage gap and socioeconomic development (r = -0.63, P = 0.01). Coverage of MCH services and socioeconomic development has a significant disparity in the districts of Jammu and Kashmir. Resource-rich and more urbanized districts are much ahead of the poor and less urbanized districts in terms of the usage of MCH services.


[Indications for the surgical intervention in endocrine disorders of the ovaries].
Endocrine disturbances of the ovaries with indication for surgery are rare. They require close cooperation between paediatric endocrinologist and paediatric surgeon. Clarification is mainly based on endocrinological findings and ultrasound examination of the ovaries. The following disturbances are discussed: Central (genuine and peripheral or pseudo-) precocious puberty, hormonally active ovarian tumours and cysts, the various forms of dysgenesis of the gonads, especially tumour-prone mixed gonadal dysgenesis with XO/XV karyotype, the syndromes of polycystic ovaries, and girls who grew up as boys with male external genitals.


Impact of COVID-19 on surgical residency training programs in Mexico City: The third victim of the pandemic. A resident's perspective.
The aim of this study is to assess the perceptions of the impact of health-care disruption due to COVID-19 on the academic training and skills of surgical trainees. We developed a 32-question survey assessing the clinical and surgical impact of COVID-19 on surgical training programs and proposals to compensate for the decrease in surgical education. We got 453 responses of surgical trainees in Mexico City. Sixty-six percent of the respondents answered that their centers had converted to the exclusive attention of COVID-19 patients. Ninety-five percent reported a decrease in surgical skills learning and 91.8% reported a decrease to clinical exposure. On proposals, 75.6% reported that it is essential to take the necessary measures to recover the clinical and surgical milestones lost. In the binary logistic regression analysis, we found that the postgraduate year (≥ PG-Y3) was statistically significant factor (p ≤ 0.000) related to a favorable opinion to developing an academic contingency plan and postponing the end of the academic residency year. More than 90% of the survey respondents reported having been affected by COVID-19 mitigation strategies. Our data calls for urgent training adjustments by hospital and university program leaders to mitigate downstream educational repercussions.


Effect of Water pH on the Uptake of Acidic (Ibuprofen) and Basic (Propranolol) Drugs in a Fish Gill Cell Culture Model.
Water pH is predicted to affect the uptake of ionizable pharmaceuticals in fish. The current study used an in vitro primary fish gill cell culture system to assess the effect of pH values in the range of 4.5-8.75 on the uptake rates of the base propranolol (pKa 9.42) and the acid ibuprofen (pKa 4.59). The rate-limiting step in the uptake was the diffusive supply flux of the unionized form from the water to the apical membrane, with subsequent rapid transfer across the epithelium. Computed uptake rate based on the unionized fraction best described the uptake of propranolol and ibuprofen over the range of pH values 5-8 and 6-8.75, respectively. For ibuprofen, the computed uptake rate overestimated the uptake below pH 6 where the unionized fraction increased from 4% at pH 6 to 55% at pH 4.5. As the unionized fraction increased, the uptake rate plateaued suggesting a saturation of the transport process. For both drugs, large variations in the uptake occur with only small fluctuations in pH values. This occurs between pH values 6 and 8, which is the pH range acceptable in regulatory test guidelines and seen in most of our freshwaters.


Synthetic domain walls in [TbFeGa/TbFe]2 multilayers.
Here we report the possibility of creating synthetic domain walls in nominal [Fe72Ga28/Tb33Fe67]2 multilayers. The magnetization as a function of the temperature reveals the absence of Compensation temperature in the samples which can be understood considering an interdiffusion process that results in the formation of TbFeGa alloys at the nominal FeGa layers. Therefore, samples actually comprise TbFeGa and TbFe layers. The hysteresis loops exhibit magnetization steps related to the nucleation of domain walls formed because of the competition between different interactions: (i) the antiferromagnetic exchange coupling between the heavy rare earth (Tb) and the transition magnetic metal (Fe) inside each layer, (ii) the antiferromagnetic coupling between Tb and Fe at the interfaces, and (iii) the Zeeman energy. In good agreement with the experimental values, the nucleation field of the domain walls has been theoretically calculated taking into account the tilt of the magnetization with respect to the sample plane. Our experimental results indicate that by a proper thickness adjustment, it can be tuned, both the value of the nucleation field and the layer in which this firstly occurs. Experimental values for the exchange bias field have also been calculated.


Health and economic outcomes of 20-valent pneumococcal conjugate vaccine compared to 15-valent pneumococcal conjugate vaccine strategies for adults in Greece.
Higher valency pneumococcal conjugate vaccines (PCVs) are expected to improve protection against pneumococcal disease through coverage of additional serotypes. The aim of the present study was to evaluate the cost-effectiveness of 20-valent pneumococcal conjugate vaccine (PCV20) compared to 15-valent pneumococcal conjugate vaccine (PCV15) alone or followed by 23-valent polysaccharide vaccine (PPV23) for adults in Greece. A published Markov model was adapted to simulate lifetime risk of clinical and economic outcomes from the public payer's perspective. The model population was stratified based on age and risk profile (i.e., low, moderate, or high-risk of developing pneumococcal disease). Epidemiologic parameters, serotype coverage and vaccines' effectiveness were based on published literature, while direct medical costs (prices €, 2022) were obtained from official sources. Main model outcomes were projected number of invasive pneumococcal disease (IPD) and all-cause non-bacteremic pneumonia (NBP) cases and attributable deaths, costs and quality-adjusted life-years (QALY) for each vaccination strategy. Sensitivity analyses were performed to ascertain the robustness of model results. Over the modeled time horizon, vaccination with PCV20 compared to PCV15 alone or PCV15 followed by PPV23 prevents an additional 747 and 646 cases of IPD, 10,334 and 10,342 cases of NBP and 468 and 455 deaths respectively, resulting in incremental gain of 1,594 and 1,536 QALYs and cost savings of €11,183 and €48,858, respectively. PSA revealed that the probability of PCV20 being cost-effective at the predetermined threshold of €34,000 per QALY gained was 100% compared to either PCV15 alone or the combination of PCV15 followed by PPV23. PCV20 is estimated to improve public health by averting additional pneumococcal disease cases and deaths relative to PCV15 alone or followed by PPV23, and therefore translates to cost-savings for the public payer. Overall results showed that vaccination with PCV20 was estimated to be a dominant vaccination strategy (improved health outcomes with reduced costs) over PCV15 alone or followed by PPV23 for prevention of pneumococcal disease in adults in Greece.


Special anesthesia considerations for the elderly plastic surgery patient.
Elderly patients may be at greater risk for perioperative complications and mortality due to an increased prevalence of age-related concomitant diseases, often more than one at a time, and a basic decline in organ functioning over time. Risks associated with age in the plastic surgery population may be minimized by a better understanding of the physiologic changes as well as the preoperative and postoperative considerations in caring for this special group of patients. The purpose of this article is to review the changes that occur with aging and the nursing care implications necessary to minimize the associated risks with anesthesia and plastic surgery.


[Distribution behavior of lipophilic drugs in the oil-in-water microemulsions].
Distribution behavior of lipophilic drugs in the oil-in-water (O/W) microemulsions was studied. Fluorescence spectra analysis was performed to investigate the effect of the compositions of microemulsions on the fluorescence spectra of armillarisin and ofloxacin which were used as the model drugs. The fluorescence spectra of the model drugs in the microemulsions with various amount of the compositions were compared. The results showed that the armillarisin were both localized in the interfacial film of microemulsion systems with both phenylmethanol and PEG 400 as the co-surfactants, separately. Ofloxacin was localized in the interfacial film of microemulsion systems with Gradamol GTCC as the oil phase, but in the oil pool of microemulsion systems with oleic acid/olive oil (OA/OO) (1:1) as the oil phase. Besides, it was found that the drug would have the tendency to locate in the microenvironment where the composition with the largest solubility to model drug is located, and its actual localized position would be dependent on the amount of this composition. The results indicate that the localized region of lipophilic drug in the O/W microemulsion systems is related with the solubility of the model drug in various compositions.


[Therapeutic problems of cancers of the gallbladder].
Data of 32 patients who were operated for gallbladder carcinoma were evaluated in a retrospective meta-analysis. Results were compared with endoscopic retrograde cholangio-drainage (ERCP) using large size 12/14-French gauge endo-prostheses with side flaps to prevent migration. According to the TNM classification 84% of patients were classified as stage IV, 12.5% were in a stage III and 3% were in a stage II. Only 22% of cases were operated for cure (cholecystectomies, lymphadenectomy, wedge resection of the liver). All patients died in between one year on cancer, average survival was 158 days in TNM stage II, 183 days in stage III and 75 days in stage IV. Early complication rate was in stage III and 75 days in stage IV. Early complication rate was at 28% due to cardiac and pulmonary complications. No one died as a result of the operation. Endoscopic bile duct drainage (ERCP) for gallbladder carcinoma (n = 21) was shown to be superior to surgical results with an average survival of 160 days. Early complication rate (30 day interval) was at 5.6% (n = 1014), mostly due to tube occlusion with cholangitis; clinical mortality was 2.6% only (n = 393). Occlusion of the endoscopic 12/14-French gauge tube was seen after 213 days in average. Endoscopic therapy was shown to represent an independent way in gallbladder cancer treatment not only for patients defined as not suitable for operation. All own results were compared to the literature, therapeutic regimen in gallbladder carcinoma is summarized as an organigramm.


Bioavailability challenges associated with development of anti-cancer phenolics.
Phenolics including many polyphenols and flavonoids have the potentials to become chemoprevention and chemotherapy agents. However, poor bioavailability limits their biological effects in vivo. This paper reviews the factors that affect phenolics absorption and their bioavailabilities from the points of view of their physicochemical properties and disposition in the gastrointestinal tract. The up-to-date research data suggested that solubility and metabolism are the primary reasons that limit phenolic aglycones' bioavailability although stability and poor permeation may also contribute to the poor bioavailabilities of the glycosides. Future investigations should further optimize phenolics' bioavailabilities and realize their chemopreventive and chemotherapeutic effects in vivo.


Diabetic papillopathy treated with intravitreal ranibizumab.
In this report, we present a case of diabetic papillopathy that resolved after a single dose of intravitreal ranibizumab injection. A 50-year-old male presented with painless visual loss in his right eye. His visual acuity was 1/10 in the right eye and 10/10 in the left eye. Anterior segment examination of both eyes was unremarkable. Posterior segment of the right eye showed nonproliferative diabetic retinopathy with a swollen optic disc. Fluorescein angiography and optical coherence tomography were performed. There was dye leakage from the right optic disc. Optical coherence tomography revealed a significant increase in retinal nerve fiber layer thickness. Magnetic resonance imaging of the brain and orbit were normal. The patient received a single intravitreal ranibizumab (0.5 mg) injection. Two weeks after the injection, there was a marked regression of the disc swelling. Three months after the injection the optic disc was pallor and visual acuity was 6/10.


Determination of type 1 poliovirus subtype classes with neutralizing monoclonal antibodies.
Hybridomas secreting neutralizing monoclonal antibodies (MA) against type 1 poliovirus were developed by fusion of mouse myeloma cells with splenocytes of immunized mice. Strain-specific MA selected for their capacity to neutralize wild (Mahoney) or attenuated (Sabin, LSc 2ab) poliovirus strains were used for identification of field isolates. A simple and reliable neutralization-index-assay was developed and used to test for intratypic serodifferentiation of poliovirus with the selected MA. Three subtype classes of type 1 poliovirus have so far been identified by testing 4 reference strains and 96 field isolates: Mahoney-like, LSc-like, and strains not recognized by either anti-Mahoney or anti-LSc MA. Neutralizing MA proved an excellent tool for unequivocal antigenic characterization of different poliovirus strains.


A cosolvency model to predict solubility of drugs at several temperatures from a limited number of solubility measurements.
A cosolvency model to predict the solubility of drugs at several temperatures was derived from the excess free energy model of Williams and Amidon. The solubility of oxolinic acid, an antibacterial drug, was measured in aqueous (water+ethanol) and non-aqueous (ethanol+ethyl acetate) mixtures at several temperatures (20, 30, 35, 40 degrees C). Oxolinic acid displays a solubility maximum in each solvent mixture at solubility parameter values of 32 and 22 MPa(1/2). The temperature and heat of fusion were determined from differential scanning calorimetry. The solvent mixtures do not produce any solid phase change during the solubility experiments. The experimental results and those from the literature were employed to examine the accuracy and prediction capability of the proposed model. An equation was obtained to represent the drug solubility changes with cosolvent concentration and temperature. The model was also tested using a small number of experimental solubilities at 20 and 40 degrees C showing reasonably accurate predictions. This is important in pharmaceutics because it save experiments that are often expensive and time consuming.


Disseminated intravascular coagulation due to intravenous administration of hetastarch.
Disseminated intravascular coagulation occurred in a patient after intravenous administration of hetastarch. The onset was acute within 3 hours after exposure to the agent and the course was fulminating. The patient died in 48 hours. Clinical, hematologic, and pathologic features are presented and possible pathophysiologic mechanism is discussed. In view of this experience and documented effects of hetastarch on coagulation, the use of hetastarch should be avoided if the patient has a history of coagulation disorder, and the patient receiving the agent should be closely monitored with appropriate coagulation tests.


Safe handling of vaccines: the rewards of rigorous routines.
A recent report published by the Office of Inspector General (OIG) entitled Vaccines for Children Program: Vulnerabilities in Vaccine Management has brought to public awareness the need for increased attention to safe handling of vaccines. The maximum benefit of receiving vaccines for vaccine-preventable diseases can only be attained when we ensure that safe storage and handling occurs through strict adherence to the vaccine cold chain. This compliance can best be accomplished by identifying a vaccine coordinator that is intimately familiar with the components of the vaccine cold chain and provides the necessary oversight to ensure that all links in the chain are maintained. Utilization of helpful resources, including the Centers for Disease Control and Prevention (CDC) resources related to safe handling of vaccines, is central to a well defined process for vaccine handling. This adherence provides reassurance, both to patients receiving vaccine and providers administering it, that the safest and most effective vaccine is being delivered.


End-product regulation of the tryptophan-nicotinic acid pathway in Neurospora crassa.
The regulation of the tryptophan-nicotinic acid pathway in Neurospora crassa was examined with mutants (nic-2, nic-3) which require nicotinamide for growth. The accumulation of N-acetylkynurenin and 3-hydroxyanthranilic acid by these mutants served to estimate the level of function of the early reactions in the pathway. In still cultures, maximal accumulation occurred with media containing growth-limiting amounts of nicotinamide; the accumulation of intermediates was almost negligible with nicotinamide in excess. Only nicotinamide and closely related compounds which also supported the growth of these mutants inhibited the accumulation of intermediates. The site of inhibition was assessed to be between tryptophan and kynurenin (or N-acetylkynurenin). The synthesis of N-acetylkynurenin was examined in washed germinated conidia suspended in buffer; the level of N-acetylkynurenin-synthesizing activity was inversely related to the concentration of nicotinamide in the germination medium. The addition of large amounts of nicotinamide to suspensions of germinated conidia did not affect their N-acetylkynurenin-synthesizing activity. Formamidase activity, kynurenin-acetylating activity, and gross tryptophan metabolism in germinated conidia was not influenced by the concentration of nicotinamide in the germination medium. The results obtained indicate that the site of inhibition by nicotinamide is the first step in the pathway, the tryptophan pyrrolase reaction. The data are interpreted as nicotinamide or a product thereof, such as nicotinamide adenine dinucleotide, acting as a repressor of the formation of tryptophan pyrrolase in N. crassa.


Routine screening of Indigenous cancer patients' unmet support needs: a qualitative study of patient and clinician attitudes.
Indigenous Australians have poorer cancer outcomes in terms of incidence mortality and survival compared with non-Indigenous Australians. The factors contributing to this disparity are complex. Identifying and addressing the psychosocial factors and support needs of Indigenous cancer patients may help reduce this disparity. The Supportive Care Needs Assessment Tool for Indigenous People (SCNAT-IP) is a validated 26-item questionnaire developed to assess their unmet supportive care needs. This qualitative study reports on patient and clinician attitudes towards feasibility and acceptability of SCNAT-IP in routine care. Forty-four in-depth semi-structured interviews were conducted with 10 clinical staff and 34 Indigenous cancer patients with heterogeneous tumours. Participants were recruited from four geographically diverse Australian cancer clinics. Transcripts were imported into qualitative analysis software (NVivo 10 Software), coded and thematic analysis performed. Indigenous patients (mean age 54.4 years) found the SCNAT-IP beneficial and easy to understand and they felt valued and heard. Clinical staff reported multiple benefits of using the SCNAT-IP. They particularly appreciated its comprehensive and systematic nature as well as the associated opportunities for early intervention. Some staff described improvements in team communication, while both staff and patients reported that new referrals to support services were directly triggered by completion of the SCNAT-IP. There were also inter-cultural benefits, with a positive and bi-directional exchange of information and cultural knowledge reported when using the SCNAT-IP. Although staff identified some potential barriers to using the SCNAT-IP, including the time required, the response format and comprehension difficulties amongst some participants with low English fluency, these were outweighed by the benefits. Some areas for scaled improvement were also identified by staff. Staff and patients found the SCNAT-IP to be an acceptable tool and supported universal screening for Indigenous cancer patients. The SCNAT-IP has the potential to help reduce the inequalities in cancer care experienced by Indigenous Australians by identifying and subsequently addressing their unmet support needs. Further research is needed to explore the validity of the SCNAT-IP for Indigenous people from other nations.


Single-Artery Human Ear Graft Procurement: A Simplified Approach.
In the field of experimental facial vascularized composite tissue allotransplantation, a human auricular subunit model, pedicled on both superficial temporal and posterior auricular arteries, was described. Clinical cases of extensive auricular replantation, however, suggested that a single artery could perfuse the entire flap. In this study, variants of this single-pedicle approach have been studied, aiming to develop a more versatile replantation technique, in which the question of venous drainage has also been addressed. For arterial perfusion study, the authors harvested 11 auricular grafts, either on a single superficial temporal artery pedicle (n = 3) or a double superficial temporal and posterior auricular artery pedicle (n = 8). The authors then proceeded to selective barium injections, in the superficial temporal, posterior auricular, or both superficial temporal and posterior auricular arteries. Arteriograms were acquired with a micro-computed tomographic scan and analyzed on three-dimensionally reconstructed images. Venous drainage was investigated in eight hemifaces, carefully dissected after latex injection. Observations showed a homogenous perfusion of the whole auricle in all arterial graft variants. Venous drainage was highly variable, with either a dominant superficial temporal vein (37.5 percent), dominant posterior auricular vein (12.5 percent), or co-dominant trunks (50 percent). The authors demonstrated that auricular subunit vascularized composite tissue allotransplantation can be performed on a single artery, relying on the dynamic intraauricular anastomoses between superficial temporal artery and posterior auricular branches. Potentially, this vascular versatility is prone to simplify the subunit harvest and allows various strategies for pedicle selection. Venous drainage, however, remains inconstant and thus the major issue when considering auricular transplantation. Therapeutic, V.


In vitro study of accuracy of subaxial cervical pedicle screw insertion using calipers based on the gravity line.
There is a high probability of iatrogenic perforation of the vertebral pedicle wall during the application of subaxial cervical pedicle screw (CPS). The goal of this study was to evaluate the accuracy of CPS insertion at C3-C7 in vitro using novel calipers based on the gravity line. Nine cadaveric cervical spines underwent computed tomography scanning and preoperative design. A lateral fluoroscopic view was taken to measure the intra-operative sagittal angle by C-arm with hanging cross structured K-wires. By referring to the gravity line, caliper A was used to locate the entry point, while caliper B was employed to guide the screw insertion. Postoperative CT scans were performed to assess the accuracy of the screw placements, according to the Neo classification. Overall, 78 (88.6%) of the 88 pedicle screw placements were classified as grade 0 (correct position), 4 (4.5%) were grade 1 (non-critical perforation), 4 (4.5%) were grade 2 (critical perforation), and 2 (2.3%) were grade 3 (critical perforation). Using our novel calipers and referring to the gravity line was helpful for locating and guiding individual cervical pedicle screw insertions.


Heat Transfer and Temperature Characteristics of a Working Digital Camera.
Digital cameras represented by industrial cameras are widely used as image acquisition sensors in the field of image-based mechanics measurement, and their thermal effect inevitably induces thermal-induced errors of the mechanics measurement. To deeply understand the errors, the research for digital camera's thermal effect is necessary. This study systematically investigated the heat transfer processes and temperature characteristics of a working digital camera. Concretely, based on the temperature distribution of a typical working digital camera, the heat transfer of the working digital camera was investigated, and a model describing the temperature variation and distribution was presented and verified experimentally. With this model, the thermal equilibrium time and thermal equilibrium temperature of the camera system were calculated. Then, the influences of thermal parameters of digital camera and environmental temperature on the temperature characteristics of working digital camera were simulated and experimentally investigated. The theory analysis and experimental results demonstrate that the presented model can accurately describe the temperature characteristics and further calculate the thermal equilibrium state of working digital camera, all of which contribute to guiding mechanics measurement and thermal design based on such camera sensors.


A Plutocratic Proposal: an ethical way for rich patients to pay for a place on a clinical trial.
Many potential therapeutic agents are discarded before they are tested in humans. These are not quack medications. They are drugs and other interventions that have been developed by responsible scientists in respectable companies or universities and are often backed up by publications in peer-reviewed journals. These possible treatments might ease suffering and prolong the lives of innumerable patients, yet they have been put aside. In this paper, we outline a novel mechanism-the Plutocratic Proposal-to revive such neglected research and fund early phase clinical trials. The central idea of the Proposal is that any patient who rescues a potential therapeutic agent from neglect by funding early phase clinical trials (either entirely or in large part) should be offered a place on the trial.


Site of deposition and factors affecting clearance of aerosolized solute from canine lungs.
We determined the influence of several factors on lung solute clearance using aerosolized 99mTc-diethylenetriaminepentaacetate. We used a jet nebulizer-plate separator-balloon system to generate particles with an activity median aerodynamic diameter of 1.1 micron, administered the aerosol in a standard fashion, and determined clearance half times (t1/2) with a gamma-scintillation camera. The following serial studies were performed in five anesthetized, paralyzed, intubated, mechanically ventilated dogs: 1) control, with ventilatory frequency (f) = 15 breaths/min and tidal volume (VT) = 15 ml/kg during solute clearance; 2) repeat control, for reproducibility; 3) increased frequency, with f = 25 breaths/min and VT = 10 ml/kg; 4) positive end-expiratory pressure (PEEP) of 10 cmH2O; 5) unilateral pulmonary arterial occlusion (PAO); and 6) bronchial arterial occlusion (BAO). Control t1/2 was 25 +/- 5 min and did not change in the repeat control, increased frequency, or BAO experiments. PEEP markedly decreased t1/2 to 13 +/- 3 min (P less than 0.01), and PAO increased it to 37 +/- 6 min (P less than 0.05). We conclude that clearance from the lungs by our method is uninfluenced by increased frequency, increases markedly with PEEP, and depends on pulmonary, not bronchial, blood flow.


Evidence for circulating cancer stem-like cells and epithelial-mesenchymal transition phenotype in the pleurospheres derived from lung adenocarcinoma using liquid biopsy.
Lung cancer stem cells are supposed to be the main drivers of tumor initiation, maintenance, drug resistance, and relapse of the disease. Hence, identification of the cellular and molecular aspects of these cells is a prerequisite for targeted therapy of lung cancer. Currently, analysis of circulating tumor cells has the potential to become the main diagnostic technique to monitor disease progression or therapeutic response as it is non-invasive. However, accurate detection of circulating tumor cells has remained a challenge, as epithelial cell markers used so far are not always trustworthy for detecting circulating tumor cells, especially during epithelial-mesenchymal transition. As cancer stem cells are the only culprit to initiate metastatic tumors, our aim was to isolate and characterize circulating tumor stem cells rather than circulating tumor cells from the peripheral blood of NSCLC adenocarcinoma as limited data are available addressing the gene expression profiling of lung cancer stem cells. Here, we reveal that CD44(+)/CD24(-) population in circulation not only exhibit stem cell-related genes but also possess epithelial-mesenchymal transition characteristics. In conclusion, the use of one or more cancer stem cell markers along with epithelial, mesenchymal and epithelial mesenchymal transition markers will prospectively provide the most precise assessment of the threat for recurrence and metastatic disease and has a great potential for forthcoming applications in harvesting circulating tumor stem cells and their downstream applications. Our results will aid in developing diagnostic and prognostic modalities and personalized treatment regimens like dendritic cell-based immunotherapy that can be utilized for targeting and eliminating circulating tumor stem cells, to significantly reduce the possibility of relapse and improve clinical outcomes.


Medium to long-term functional outcome of patients after chemonucleolysis.
Chemonucleolysis is an established modality in the treatment of lumbar disc prolapse and has been widely used for over 39 years since its introduction by Lyman Smith in 1963. We report the medium to long-term functional outcome of patients who had chemonucleolysis for single level disc prolapse. One hundred and twelve patients were reviewed retrospectively with a mean follow-up of 9.5 years. The Oswestry Disability Index questionnaire was used to estimate the functional outcome of chemonucleolysis. An excellent or good response occurred in 79 patients (70.5%) while 12 patients (10.7%) showed moderate response with minimal disability. Treatment failed in 21 patients (18.5%) who showed poor response and 12 of these 21 patients went for surgery within a mean period of 6 months. One patient had surgery at a different level than chemonucleolysis. There was only one incident of procedure termination because of epidural contrast leak. There was no case of anaphylaxis or discitis. We concluded on the basis of our results that in carefully selected patients, chemonucleolysis is a safe and effective treatment modality for lumbar disc herniation with good medium to long-term functional outcome.


Impact of mass distribution of long-lasting insecticide nets on the incidence of malaria in Lomami, Democratic Republic of Congo: a study based on electronic health record data (2018 - 2019).
holoendemic, malaria remains one of the major public health problems in Lomami Province in the Democratic Republic of Congo (DRC). To fight against it, a free mass distribution of long-lasting insecticide nets (LLINs) was organized in July 2019 throughout the province. The present study aimed to assess the incidence of malaria and its impact on anaemia of children from 0 to 59 months in this region before and after this intervention. we had conducted a retrospective observational study from June to December 2018 and June to December 2019. The data were collected on District Health Information System version two (DHIS2) and analyzed with T-tests to compare the incidence rates before (second semester 2018) and after the distribution of LLINs (second semester 2019). the evolution of malaria cases immediately dropped after the distribution campaign. The incidence rates per 1,000 inhabitants in 2018 and 2019 were 106 and 107 respectively in the general population; 302 versus 305 in children aged 0 to 59 months and 219 versus 209 in pregnant women. The differences in incidence were not statistically significant with p values 0.497, 0.4602, and 0.3097 respectively. However, it was observed that the decrease in malaria cases led to a decrease in anaemia cases in general. the LLIN distribution campaign did not decrease the incidence of malaria. The synergy of preventive interventions to reduce the incidence of malaria remains key.


An Examination of Four Traditional School Physical Activity Models on Children's Step Counts and MVPA.
Schools have been identified as primary societal institutions for promoting children's physical activity (PA); however, limited evidence exists demonstrating which traditional school-based PA models maximize children's PA. The purpose of this study was to compare step counts and moderate-to-vigorous physical activity (MVPA) across 4 traditional school PA modules. Step count and MVPA data were collected on 5 consecutive school days from 298 children (Mage = 10.0 ± 0.6 years; 55% female) in Grade 5. PA was measured using the NL-1000 piezoelectric pedometer. The 4 models included (a) recess only, (b) multiple recesses, (c) recess and physical education (PE), and (d) multiple recesses and PE. Children accumulated the greatest PA on days that they had PE and multiple recess opportunities (5,242 ± 1,690 steps; 15.3 ± 8.8 min of MVPA). Children accumulated the least amount of PA on days with only 1 recess opportunity (3,312 ± 445 steps; 7.1 ± 2.3 min of MVPA). Across all models, children accumulated an additional 1,140 steps and 4.1 min of MVPA on PE days. It appears that PE is the most important school PA opportunity for maximizing children's PA. However, on days without PE, a 2nd recess can increase school PA by 20% (Δ = 850 steps; 3.8 min of MVPA).


Synergistic Inhibitory Effects of Cetuximab and Cisplatin on Human Colon Cancer Cell Growth via Inhibition of the ERK-Dependent EGF Receptor Signaling Pathway.
The purpose of this study was to evaluate the anticancer efficacy of cetuximab combined with cisplatin (combination treatment) on colon cancer growth, as well as its underlying action mechanism. Combination treatment synergistically potentiated the effect of cetuximab on cell growth inhibition and apoptosis induction in HCT116 and SW480 cells. Combination treatment further suppressed the expression of the activated form of epidermal growth factor receptor (EGFR) and MAP kinase (p-ERK and p-p38) and also significantly inhibited the activity of activator protein-1 (AP-1) and nuclear factor kappa B (NF-κB). Additionally, the expression of cyclooxygenase-2 (COX-2) and interleukin-8 (IL-8) mRNA was significantly reduced by the combination treatment as compared to the expression seen for treatment with cetuximab or cisplatin alone. We found that the synergistic inhibitory effects of cetuximab and cisplatin on AP-1 and NF-κB activation, as well as on cell viability, were reversed by pretreatment with an ERK inhibitor. Results demonstrate that combined treatment with cetuximab and cisplatin exerts synergistic anticancer effects on colon cancer cells and also suggest that the ERK pathway plays a critical role in these effects via the suppression of the EGFR signaling pathway, along with the inhibition of COX-2, IL-8, and AP-1 and NF-κB.


A thirst for the authentic: craft drinks producers and the narration of authenticity.
There is a long academic tradition which positions the desire for authenticity as emerging as a symptom of dissatisfactions with modernity. Most recently, this has involved consumption of products that are valued for being authentic in contrast to mass produced commodities which are seen as being homogeneous, standardized and therefore inauthentic. A recent resurgence in interest in the idea of craft and craftwork has brought to the fore concerns about re-establishing connections between products, consumers and producers beyond rational market exchange. This research draws on interviews with 40 craft brewery and distillery workers to explore the ways in which authenticity is narrated as part of an ongoing effort to add value to their products and the contexts of their production. The article identifies six modes of authenticity which are drawn on in combination by participants to establish a narrative of authenticity. This is understood to be a clear illustration of the 'enrichment process' by which post-industrial economies manufacture value. A central element of craft drink producers' work is the marshalling of cultural value and engaging in communicative and performative acts that ascribe that value to products and the people involved in making them.


Rho-associated kinase is a therapeutic target in neuroblastoma.
Neuroblastoma is a peripheral neural system tumor that originates from the neural crest and is the most common and deadly tumor of infancy. Here we show that neuroblastoma harbors frequent mutations of genes controlling the Rac/Rho signaling cascade important for proper migration and differentiation of neural crest cells during neuritogenesis. RhoA is activated in tumors from neuroblastoma patients, and elevated expression of Rho-associated kinase (ROCK)2 is associated with poor patient survival. Pharmacological or genetic inhibition of ROCK1 and 2, key molecules in Rho signaling, resulted in neuroblastoma cell differentiation and inhibition of neuroblastoma cell growth, migration, and invasion. Molecularly, ROCK inhibition induced glycogen synthase kinase 3β-dependent phosphorylation and degradation of MYCN protein. Small-molecule inhibition of ROCK suppressed MYCN-driven neuroblastoma growth in TH-MYCN homozygous transgenic mice and MYCN gene-amplified neuroblastoma xenograft growth in nude mice. Interference with Rho/Rac signaling might offer therapeutic perspectives for high-risk neuroblastoma.


Efficacy of the Perfluoro-N-Octane-Assisted Single-Layered Inverted Internal Limiting Membrane Flap Technique for Large Macular Holes.
The aim of this study was to evaluate the efficacy of the perfluoro-n-octane-assisted single-layered inverted internal limiting membrane (ILM) flap for large macular holes (MHs). We reviewed idiopathic MHs >400 μm. The patients were divided into ILM peeling (group P, 51 eyes) and ILM flap (group F, 41 eyes). Closure of MHs, best-corrected visual acuity (BCVA), and postoperative optical coherence tomography findings were analyzed. MH closure was achieved in 88.2% in group P and in 100% in group F (p = 0.032). SF6 and air was used most frequently in groups P and F, respectively. Both had a significant improvement in BCVA, which was better in group F until 3 months, but not at 6 months. At 6 months, the ellipsoid zone and external limiting membrane were restored with no significant difference. The single-layered inverted ILM flap was better for the closure of large MHs than ILM peeling, without using long-acting gas that prevents early rehabilitation.


Court orders Immigration and Refugee Board to take into account evidence of HIV-related discrimination.
On 31 August 2004, the Federal Court granted an HIV-positive woman's application for judicial review of a decision by the Immigration and Refugee Board (IRB). The issue before the court was whether the Board erred by ignoring documentary evidence before it with respect to the treatment of people living with HIV/AIDS in Nigeria. The court ordered that a newly constituted panel redetermine the claim in light of evidence of the discrimination faced by HIV-positive people in Nigeria.


Regulation of ectodermal differentiation in Xenopus laevis animal caps treated with TPA and ammonium chloride.
Animal caps isolated from Xenopus laevis embryos at the blastula stage were treated sequentially with NH4Cl, a known cement gland inducer, and with 12-O-tetradecanoyl phorbol-13-acetate (TPA), a known neural inducer. The two artificial inducers were also used in reverse order to see if they can mimic the natural inducers acting during the progressive determination of the ectodermal organ. Immunofluorescence and whole-mount in situ hybridization were used to study the expression of tubulin, taken to indicate an early step on the pathway of cell elongation, and neural cell adhesion molecule (N-CAM) taken to indicate an early step in the determination of the nervous system. The expression of XCG-1, a marker of early specification of the cement gland, was also studied. The results showed that the two artificial inducers can mimic the effects of the natural inducers in animal cap explants. The TPA behaves like a neural inducer, reducing the number and the extension of the cement gland when added to the medium in addition to NH4Cl, before or after NH4Cl treatment. In the process of cement gland/neural induction, it is possible to redirect the ectoderm already specified as cement gland to neural tissue, but it does not seem possible to respecify the neural tissue as cement gland. Moreover, the animal caps were also cut into dorsal and ventral parts and the two halves were treated separately. The results were similar to those obtained with treatment of the entire animal cap, suggesting that a dorsal-ventral pattern is not yet established before the gastrula stage, and that in normal embryos there are boundaries between the effects of different inducers.


Differential timing of defense-related responses induced by cerato-platanin and cerato-populin, two non-catalytic fungal elicitors.
The cerato-platanin (CP) family consists of fungal-secreted proteins involved in various stages of the host-fungus interaction and acting as phytotoxins and elicitors of defense responses. The founder member of this family is CP, a non-catalytic protein with a six-stranded double-ψβ-barrel fold. Cerato-populin (Pop1) is an ortholog showing low sequence identity with CP. CP is secreted by Ceratocystis platani, the causal agent of the canker stain of plane. Pop1 is secreted by Ceratocystis populicola, a pathogen of poplar. CP and Pop1 have been suggested to act as PAMPs (pathogen-associated molecular patterns) because they induce phytoalexin synthesis, transcription of defense-related genes, restriction of conidia growth and cell death in various plants. Here, we treated plane leaves with CP or Pop1, and monitored defense responses to define the role of these elicitors in the plant interactions. Both CP and Pop1 were able to induce mitogen-activated protein kinases (MAPKs) phosphorylation, production of reactive oxygen species and nitric oxide, and overexpression of defense related genes. The characteristic DNA fragmentation and the cytological features indicate that CP and Pop1 induce cell death by a mechanism of programmed cell death. Therefore, CP and Pop1 can be considered as two novel, non-catalytic fungal PAMPs able to enhance primary defense. Of particular interest is the observation that CP showed faster activity compared to Pop1. The different timing in defense activation could potentially be due to the structural differences between CP and Pop1 (i.e. different hydrophobic index and different helix content) therefore constituting a starting point in unraveling their structure-function relationships.


Improved pressure-frequency sensing subxiphoid pericardial access system: performance characteristics during in vivo testing.
We have designed, synthesized, and tested an improved version of our original subxiphoid access system intended to facilitate epicardial electrophysiology. The new version of the system incorporates a precision fiber-optic pressure sensor and a novel signal analysis algorithm for identifying pressure-frequency signatures which, in the clinical setting, may allow for safer access to the pericardial space. Following in vivo studies on ten adult canine models, we analyzed 215 pressure-frequency measurements made at the distal tip of the access needle, of which 98 were from nonpericardial, 112 were from pericardial, and five were from ventricular locations. The needle locations as identified by the algorithm were significantly different from each other (p < 0.01), and the algorithm had improved performance when compared to a standard fast Fourier transform (FFT) analysis of the same data. Moreover, the structure of the algorithm can potentially overcome the time lags intrinsic to FFT analysis such that the needle's location can be determined in near-real time. Hydrodynamic pressure-frequency measurements made during traversal of the pericardial membrane revealed a distinct change in signal structure between the pericardial and nonpericardial anatomy. We present and discuss the design principles, details of construction, and performance characteristics of this system.


Gamma interferon produced by antigen-specific CD4+ T cells regulates the mucosal immune responses to Citrobacter rodentium infection.
Citrobacter rodentium, a murine model pathogen for enteropathogenic Escherichia coli, colonizes the surface of intestinal epithelial cells and causes mucosal inflammation. This bacterium is an ideal model for investigating pathogen-host immune interactions in the gut. It is well known that gene transcripts for Th1 cytokines are highly induced in colonic tissue from mice infected with C. rodentium. However, it remains to be seen whether the Th1 or Th2 cytokines produced by antigen-specific CD4(+) T cells provide effective regulation of the host immune defense against C. rodentium infection. To investigate the antigen-specific immune responses, C. rodentium expressing ovalbumin (OVA-C. rodentium), a model antigen, was generated and used to define antigen-specific responses under gamma interferon (IFN-gamma)-deficient or interleukin-4 (IL-4)-deficient conditions in vivo. The activation of antigen-specific CD4(+) T cells and macrophage phagocytosis were evaluated in the presence of IFN-gamma or IL-4 in vitro. IFN-gamma-deficient mice exhibited a loss of body weight and a higher bacterial concentration in feces during OVA-C. rodentium infection than C57BL/6 (wild type) or IL-4-deficient mice. This occurred through the decreased efficiency of macrophage phagocytosis and the activation of antigen-specific CD4(+) T cells. Furthermore, a deficiency in antigen-specific CD4(+) T-cell-expressed IFN-gamma led to a higher susceptibility to mucosal and gut-derived systemic OVA-C. rodentium infection. These results show that the IFN-gamma produced by antigen-specific CD4(+) T cells plays an important role in the defense against C. rodentium.


Goal-Driven Beam Setting Optimization for Whole-Breast Radiation Therapy.
To develop an automated optimization program to generate optimal beam settings for whole-breast radiation therapy driven by clinically oriented goals. Forty patients were retrospectively included in this study. Each patient's planning images, contoured structures of planning target volumes, organs-at-risk, and breast wires were used to optimize for patient-specific-beam settings. Two beam geometries were available tangential beams only and tangential plus supraclavicular beams. Beam parameters included isocenter position, gantry, collimator, couch angles, and multileaf collimator shape. A geometry-based goal function was defined to determine such beam parameters to minimize out-of-field target volume and in-field ipsilateral lung volume. For each geometry, the weighting in the goal function was trained with 10 plans and tested on 10 additional plans. For each query patient, the optimal beam setting was searched for different gantry-isocenter pairs. Optimal fluence maps were generated by an in-house automatic fluence optimization program for target coverage and homogeneous dose distribution, and dose calculation was performed in Eclipse. Automatically generated plans were compared with manually generated plans for target coverage and lung and heart sparing. The program successfully produced a set of beam parameters for every patient. Beam optimization time ranged from 10 to 120 s. The automatic plans had overall comparable plan quality to manually generated plans. For all testing cases, the mean target V95% was 91.0% for the automatic plans and 88.5% for manually generated plans. The mean ipsilateral lung V20Gy was lower for the automatic plans (15.2% vs 17.9%). The heart mean dose, maximum dose of the body, and conformity index were all comparable. We developed an automated goal-driven beam setting optimization program for whole-breast radiation therapy. It provides clinically relevant solutions based on previous clinical practice as well as patient specific anatomy on a substantially faster time frame.


Identification of lethal mutations in yeast threonyl-tRNA synthetase revealing critical residues in its human homolog.
Aminoacyl-tRNA synthetases (aaRSs) are a group of ancient enzymes catalyzing aminoacylation and editing reactions for protein biosynthesis. Increasing evidence suggests that these critical enzymes are often associated with mammalian disorders. Therefore, complete determination of the enzymes functions is essential for informed diagnosis and treatment. Here, we show that a yeast knock-out strain for the threonyl-tRNA synthetase (ThrRS) gene is an excellent platform for such an investigation. Saccharomyces cerevisiae ThrRS has a unique modular structure containing four structural domains and a eukaryote-specific N-terminal extension. Using randomly mutated libraries of the ThrRS gene (thrS) and a genetic screen, a set of loss-of-function mutants were identified. The mutations affected the synthetic and editing activities and influenced the dimer interface. The results also highlighted the role of the N-terminal extension for enzymatic activity and protein stability. To gain insights into the pathological mechanisms induced by mutated aaRSs, we systematically introduced the loss-of-function mutations into the human cytoplasmic ThrRS gene. All mutations induced similar detrimental effects, showing that the yeast model could be used to study pathology-associated point mutations in mammalian aaRSs.


Virus isolation for diagnosing dengue virus infections in returning travelers.
Dengue fever is recognized as one of the most frequent imported acute febrile illnesses affecting European tourists returning from the tropics. In order to assess the value of virus isolation for the diagnosis of dengue fever, 70 cases of dengue fever confirmed in German travelers during the period 1993-2001 were analyzed retrospectively. In 26 patients who had developed acute febrile illness within 2 weeks following their return from a trip to a dengue-endemic area, 9 of 13 attempts to isolate the virus were successful in sera drawn 1-5 days and 2 of 13 sera drawn 6-10 days after the onset of illness. DEN-1 was the most frequent serotype isolated. If performed early, virus isolation is a reliable tool for detecting dengue virus in returning travelers.


Arterial anatomy of the lower lip.
The arterial anatomy of the lower lip was investigated in 12 sides of six fresh cadavers that had been injected systemically with a lead oxide and gelatin mixture. We found that the blood supply of the lower lip was derived from the facial artery and three dominant labial arteries: the inferior labial artery, the horizontal labiomental artery, and the vertical labiomental artery. The inferior labial artery was derived from the facial artery or superior labial artery, and ran through the submucous tissue horizontally. The horizontal labiomental artery arising from the facial artery was located between the depressor labii inferioris muscle and orbicularis oris muscle. The vertical labiomental artery arose from the submental artery. These three arteries provided small vessels that traversed vertically. These small vessels and the small branches of the facial artery, that run superficial and deep to the orbicularis oris muscle, formed a vascular network in subcutaneous and submucous tissues and minute vessels branched off to the skin, mucosa, and muscles.


The regulation of mitotic spindle function.
The process of mitosis includes a series of morphological changes in the cell in which the directional movements of chromosomes are the most prominent. The presence of a microtubular array, known as the spindle or mitotic apparatus, provides at least a scaffold upon which these movements take place. The precise mechanism for chromosome movement remains obscure, but new findings suggest that the kinetochore may play a key role in chromosome movement toward the spindle pole, and that sliding interactions between or among adjacent microtubules may provide the mechanochemical basis for spindle elongation. The physiological regulation of the anaphase motors and of spindle operation either before or after anaphase remains equally elusive. Elicitors that may serve as controlling elements in spindle function include shifts in cytosolic calcium activity and perhaps the activation or inactivation of protein kinases, which in turn produce changes in the state of phosphorylation of specific spindle components.


Lifestyle and medication interventions for the prevention or delay of type 2 diabetes mellitus in prediabetes: a systematic review of randomised controlled trials.
To assess lifestyle and pharmacological interventions aiming to delay type 2 diabetes mellitus (T2DM) in prediabetes. We searched the Cochrane Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, PsycINFO, Web of Science, BIOSIS and LILACS databases, examined reference lists and contacted authors. We included randomised controlled trials (RCTs) on both lifestyle and medication interventions in prediabetes. These studies were at least 12 month duration and aimed to delay T2DM. Four studies investigating lifestyle and medication with a total of 5,196 participants were identified. There was a high risk of bias in the studies and the interventions utilised varied considerably; thus, meta-analysis was not undertaken. The comparison between lifestyle and medication interventions was largely dependent on the intensity of the lifestyle program while we could not adequately assess their effects on cardiovascular morbidity. Adverse events with metformin and acarbose were common. There is substantial evidence that intensive lifestyle programs and medications delay T2DM in impaired glucose tolerance though it remains unclear which is more effective. Both interventions seem to be able to delay T2DM. However, both have issues with adherence and side effects and more RCTs are required.


Unusual manifestations of visceral leishmaniasis in children: a case series and its spatial dispersion in the western region of São Paulo state, Brazil.
Visceral leishmaniasis (VL) is becoming endemic in São Paulo state, in the southeastern region of Brazil. Unusual manifestations with non-specific signs and symptoms may make diagnosis difficult and delay treatment, increasing the risk of severity and death, particularly in new endemic areas. There are few studies on patients with these characteristics in Brazil. We describe a case series of unusual manifestations of VL in children and its spatial dispersion in the western region of São Paulo state. From 2009 to 2014, five clinical cases involving children treated in the Regional Hospital of Presidente Prudente (RH) were selected. Two patients had multiple relapses requiring liposomal amphotericin B; one patient had VL-cytomegalovirus-dengue co-infection and liver injury; one patient was diagnosed with X-linked agammaglobulinemia, a primary immunodeficiency; and one patient was diagnosed with VL-human immunodeficiency virus/acquired immunodeficiency syndrome (VL-HIV/AIDS) co-infection. Primary or secondary immunodeficiencies were found in four children, and associated viral infections were found in three children. Three patients were referred from other hospitals to RH. With regard to the geographic spread of VL, more cases were found in the northern area, in the epicenter of the infection where the first cases were registered, flowing south; a spatial-temporal occurrence was found. Primary and secondary immunodeficiencies and viral co-infectious should be considered among unusual manifestations of VL, especially in those with multiple relapses. Spatial-temporal occurrence was found. Thus, integrated actions and effective monitoring of the disease are needed to complement curative practices to stem the tide of the epidemic.


Rho kinase acts at separate steps in ureteric bud and metanephric mesenchyme morphogenesis during kidney development.
In this study, five different in vitro assays, which together recapitulate much of kidney development, were used to examine the role of the Rho-associated protein serine/threonine kinase (ROCK) in events central to ureteric bud (UB) and metanephric mesenchyme (MM) morphogenensis, in isolation and together. ROCK activity was found to be critical for (1) cell proliferation, growth, and development of the whole embryonic kidney in organ culture, (2) tip and stalk formation in cultures of isolated UBs, and (3) migration of MM cells (in a novel MM migration assay) during their condensation at UB tips (in a UB/MM recombination assay). Together, the data indicate selective involvement of Rho/ROCK in distinct morphogenetic processes necessary for kidney development and that the coordination of these events by Rho/ROCK provides a potential mechanism to regulate overall branching patterns, nephron formation, and thus, kidney architecture.


The experience of transition for a daughter caregiver of a stroke survivor.
The purpose of this study was to describe the experience of transition for a daughter caregiver of a stroke survivor. A phenomenologic, longitudinal case study of a woman in her late twenties provided the means by which the lived experience of transition could be studied and understood. The eleven unstructured, audiotaped interviews took place approximately every two weeks over a six and a half month period. They began six weeks after her mother's stroke and lasted until three months after her mother returned home, when life became more organized and predictable for a time. The interviews were transcribed verbatim and analyzed according to a modified version of Colaizzi's descriptive phenomenologic methodology. Since there was a temporal consideration, a time-ordered matrix was used to identify themes over time. The themes that emerged over time included: (a) changing relationships, (b) becoming a caregiver then stepping back, (c) enduring emotional turbulence, (d) taking one day at a time and (e) struggling to hang onto hope. Integration of the themes provided an exhaustive description. The experience of transition was a process that involved disruptions in close relations and daily living. The connection to a network of relationships changed to disconnection, and the fabric of interrelated lives began to unravel. The many sensations experienced were different and conflicting, revealing a rapidly changing perception of the world. An unknown future threatened to become overwhelming. Focusing on the present helped to quell the turbulent sensations experienced. An unknown future temporarily provided the opportunity to hope that daily life could once again become familiar and comfortable. The extent and object of hope changed over time. A pattern of chaos exemplified the process of transition. The passage of time revealed that life as it was known before the transition had changed. A new way of being in the world was experienced.


Attribution of changes in precipitation patterns in African rainforests.
Tropical rainforests in Africa are one of the most under-researched regions in the world, but research in the Amazonian rainforest suggests potential vulnerability to climate change. Using the large ensemble of Atmosphere-only general circulation model (AGCM) simulations within the weather@home project, statistics of precipitation in the dry season of the Congo Basin rainforest are analysed. By validating the model simulation against observations, we could identify a good model performance for the June, July, August (JJA) dry season, but this result does need to be taken with caution as observed data are of poor quality. Additional validation methods have been used to investigate the applicability of probabilistic event attribution analysis from large model ensembles to a tropical region, in this case the Congo Basin. These methods corroborate the confidence in the model, leading us to believe the attribution result to be robust. That is, that there are no significant changes in the risk of low precipitation extremes during this dry season (JJA) precipitation in the Congo Basin. Results for the December, January, February dry season are less clear. The study highlights that attribution analysis has the potential to provide valuable scientific evidence of recent or anticipated climatological changes, especially in regions with sparse observational data and unclear projections of future changes. However, the strong influence of sea surface temperature teleconnection patterns on tropical precipitation provides more challenges in the set up of attribution studies than midlatitude rainfall.


Halogen Bonding in the Complexes of CH3I and CCl4 with Oxygen-Containing Halogen-Bond Acceptors.
Methyl iodine (CH3I) and carbon tetrachloride (CCl4) are both important volatile precursors for atmospheric ozone destruction. CH3I and CCl4 can act as halogen bond donors to form molecular complexes with atmospheric organic species, such as 2,5-dihydrofuran, tetrahydrofuran, and acetone. This study characterized the halogen bonds in the CH3I and CCl4 complexes using matrix isolation infrared spectroscopy and density functional theory calculations. With the combination of vibrational frequencies in spectra and the calculated interaction energies, frequencies and atoms-in-molecules analyses, we confirmed the formation of halogen-bonded complexes. CH3I as a halogen-bond donor is comparable or slightly weaker than CCl4, and furans involving ether oxygens are better halogen acceptors than acetone. The results help to understand the possibilities of formation of atmospheric molecular complexes that may influence the atmospheric chemical activities and enhance the aerosol formation.


Single-Cell RNA Sequencing and Its Combination with Protein and DNA Analyses.
Heterogeneity in cell populations poses a significant challenge for understanding complex cell biological processes. The analysis of cells at the single-cell level, especially single-cell RNA sequencing (scRNA-seq), has made it possible to comprehensively dissect cellular heterogeneity and access unobtainable biological information from bulk analysis. Recent efforts have combined scRNA-seq profiles with genomic or proteomic data, and show added value in describing complex cellular heterogeneity than transcriptome measurements alone. With the rising demand for scRNA-seq for biomedical and clinical applications, there is a strong need for a timely and comprehensive review on the scRNA-seq technologies and their potential biomedical applications. In this review, we first discuss the latest state of development by detailing each scRNA-seq technology, including both conventional and microfluidic technologies. We then summarize their advantages and limitations along with their biomedical applications. The efforts of integrating the transcriptome profile with highly multiplexed proteomic and genomic data are thoroughly reviewed with results showing the integrated data being more informative than transcriptome data alone. Lastly, the latest progress toward commercialization, the remaining challenges, and future perspectives on the development of scRNA-seq technologies are briefly discussed.


Mössbauer study and magnetic properties of M-type barium hexaferrite doped with Co + Ti and Bi + Ti ions.
Using X-ray powder diffractions, Mössbauer spectroscopy, and magnetic measurements, the effect of complex dopants (Co2+ + Ti4+) and (Bi3+ + Ti4+) on the fine structure and magnetic properties of M-type barium hexaferrite prepared by hydroxide and carbonate precipitations has been studied. The distribution of cations over five nonequivalent positions of barium hexaferrite with magnetoplumbite structure is discussed. It has been shown that doped barium hexaferrite can be used for high-coercitivity data storage media.


Harnessing the Power of PCR Molecular Fingerprinting Methods and Next Generation Sequencing for Understanding Structure and Function in Microbial Communities.
Polymerase chain reaction (PCR) is central to methods in molecular ecology. Here, we describe PCR-dependent approaches useful for investigating microbial diversity and its function in various natural, human-associated, and built environment ecosystems. Protocols routinely used for DNA extraction, purification, cloning, and sequencing are included along with various resources for the statistical analysis following gel electrophoresis-based methods (DGGE) and sequencing. We also provide insights into eukaryotic microbiome analysis, sample preservation techniques, PCR troubleshooting, DNA quantification methods, and commonly used ordination techniques.


Myelination of the postnatal mouse cochlear nerve at the peripheral-central nervous system transitional zone.
In the nerve roots of vertebrates, the peripheral nervous system (PNS) and central nervous system (CNS) interface at the PNS-CNS transitional zone (PCTZ), which consists of cell boundaries with various myelin components. We have recently shown that the mouse cochlear nerve presents an exceptionally long segment of the CNS tissue extending into the PNS using light microscopy. However, it is unclear how oligodendrocytes and Schwann cells contribute to the formation of myelin components of the PCTZ. It is undetermined how myelination is initiated along the cochlear nerve, and when it adopts a mature pattern. In this study, immunofluorescence using antibodies specific to oligodendrocyte marker myelin oligodendrocyte glycoprotein (MOG) and Schwann cell marker myelin protein zero (MPZ) were used to detail the expression of myelin components along the postnatal mouse cochlear nerve. We found that the expression of MPZ was initially observed in the soma of bipolar spiral ganglion neurons at postnatal day 0 (P0) and progressed to the central and peripheral processes after P8-P10. Myelination of the CNS tissue was initiated in close proximity to the PCTZ from P7 to P8 and then extended centrally. Myelination of the PCTZ reached a mature style at P14, when the interface of the expression of MOG and MPZ was clearly identified along the cochlear nerve. This knowledge of PCTZ formation of the cochlear nerve will be essential to future myelination research, and it will also gain clinical interest because of its relevance to the degeneration and regeneration of the auditory pathway in hearing impairment.


Surgical wound management of the diabetic foot.
Prompt aggressive treatment of diabetic ulcerations is mandatory for healing and subsequent limb salvage. Too often the complications involving the lower extremity are overlooked or mistreated and result in amputations. The cost involved in treatment is overwhelming. In 1992, the total health care cost for patients with diabetes in the United States was 105 billion dollars. Lower extremity complications account for 15%-20% of all diabetic admissions.