Histoimmunological characterization of the cellular reaction to liver metastases induced by colon cancer cells in syngeneic rats.
Artificial liver metastases were produced by injecting in vitro cultivated colonic cancer cells into the mesenteric vein of syngeneic rats. An immunohistologic study of the inflammatory host cells infiltrating the tumors was carried out from 1 to 46 days after tumor cell injection, using a set of monoclonal antibodies labelling tumor cells, macrophages or lymphoid cells subpopulations. In small metastases, 3-7 days after tumor cell injection, tumor cell foci were surrounded by a dense corona of inflammatory cells, predominantly T lymphocytes and NK cells. This inflammatory corona regressed when metastases grew larger and completely disappeared around the large metastases found more than 28 days after cell injection. Inside the metastases, the tumor cells were mixed with a small number of cells with the characteristic labelling of macrophages (KiM2R+, W3/25+); however, the inside macrophages are OX8+ in contrast to macrophages found in normal liver and in the peritumoral corona. The progressive disappearance of the coronal inflammatory cells suggests that cancer cells are able to produce or to induce other cells to produce anti-inflammatory agents inhibiting the accumulation of macrophages and lymphoid cells around the tumors.


Analysis of pre-treatment markers predictive of treatment benefit for the therapeutic cancer vaccine MVA-5T4 (TroVax).
Cancer vaccines such as MVA-5T4 (TroVax(®)) must induce an efficacious immune response to deliver therapeutic benefit. The identification of biomarkers that impact on the clinical and/or immunological efficacy of cancer vaccines is required in order to select patients who are most likely to benefit from this treatment modality. Here, we sought to identify a predictor of treatment benefit for renal cancer patients treated with MVA-5T4. Statistical modeling was undertaken using data from a phase III trial in which patients requiring first-line treatment for metastatic renal cell carcinoma were randomized 1:1 to receive MVA-5T4 or placebo alongside sunitinib, IL-2 or IFN-α. Numerous pre-treatment factors associated with inflammatory anemia (e.g., CRP, hemoglobin, hematocrit, IL-6, ferritin, platelets) demonstrated a significant relationship with tumor burden and patient survival. From these prognostic factors, the pre-treatment mean corpuscular hemoglobin concentration (MCHC) was found to be the best predictor of treatment benefit (P < 0.01) for MVA-5T4 treated patients and also correlated positively with tumor shrinkage (P < 0.001). Furthermore, MCHC levels showed a significant positive association with 5T4 antibody response (P = 0.01). The latter result was confirmed using an independent data set comprising phase II trials of MVA-5T4 in patients with colorectal, renal and prostate cancers. Retrospective analyses demonstrated that RCC patients who had very large tumor burdens and low MCHC levels received little or no benefit from treatment with MVA-5T4; however, patients with smaller tumor burdens and normal MCHC levels received substantial benefit from treatment with MVA-5T4.


Vitamin D3 in High-Quality Cow Milk: An Italian Case Study.
The quality-labeling category of high-quality (HQ) milk defined by the Italian legislation must comply with specific requirements concerning rigorous breeder management, hygienic controls, fat and protein content, bacterial load, somatic cells, lactic acid content, and non-denatured soluble serum proteins. However, there is no specification for the vitamin D content of HQ milk. Moreover, the data on the vitamin D content of this milk category are very scarce. In the present study, the content of vitamin D3 was evaluated in HQ raw and pasteurized cow milk obtained from Italian cowsheds and supermarkets. The vitamin D3 content varied from not detected (less than 1 µg L-1) to 17.0 ± 2.0 µg L-1 milk and was not related to the milk fat content. These results represent a case study including a significant although not exhaustive part of the contemporary Italian market of HQ milk. It was shown for the first time that HQ raw milk does not necessarily contain more vitamin D3, even though non-expert consumers likely to buy milk labeled as HQ could expect it. The vitamin D3 content in HQ pasteurized whole milk should be reported on the label of the milk package as a best practice of consumer information policy.


Comparison of normative methods and the sociodental approach to assessing orthodontic treatment needs in 12-year-old schoolchildren.
To compare normative methods of orthodontic treatment need with the sociodental approach in 12-year-old students and correlate the normative measures of malocclusion with the impact of oral health on daily activities. A cross-sectional study of 201 12-year-old students was conducted in the city of Manaus, Brazil. The normative orthodontic treatment need was determined by oral clinical examination using two occlusal indices, the Index of Orthodontic Treatment Need (IOTN), comprising the Dental Health Component (DHC) and Aesthetic Component (AC ), and the Dental Aesthetic Index (DAI). The sociodental approach combined normative measures (IOTN and DAI), the impact of malocclusion on daily activities (Child-Oral Impacts on Daily Performances index, Child-OIDP) and propensity- related orthodontic treatment assessment. The normative method and the sociodental approach of orthodontic treatment needs assessment were compared using the McNemar test. The association between the impact of malocclusion on daily activities and normative orthodontic need was tested using χ2 and Kruskal-Wallis tests. The frequency of individuals with normative need according to IOTN/DHC (24.9%) and DAI (42.3%) was statistically higher when compared with the sociodental approach (<= 4.5%) (P < 0.001). The sociodental approach provided different results using IOTN/DHC (1.5%) and DAI (4.5%) (P < 0.001). The magnitude of normative need was associated with the impact of malocclusion on children's daily activities. Substantial reductions in normative need estimates for orthodontic treatment were observed using the sociodental approach. The sociodental approach for orthodontic treatment needs can optimise the use of resources in oral health services.


Umbilical transposition in functional panniculectomy of the massive weight loss patient: is it aesthetic or medically necessary?
We review the procedures used in panniculectomy and explore the necessity of umbilical transposition when adequately treating the medical and functional problems associated with panniculus in the massive weight loss patient. Thirty-five consecutive patients with symptomatic panniculus after massive weight loss undergoing panniculectomy during the time period from November 2008 to October 2010 at Denver Health Medical Center were retrospectively analyzed. Inclusion criteria consisted of insurance approval for the panniculectomy. All patients had persistent skin problems in the lower abdomen. Seven patients had additional skin problems in the skin around navel and/or mid-abdomen. Eleven patients complained of difficulty in performing activities of daily living. Nine patients had a concomitant ventral hernia repair. An infraumbilical panniculectomy was adequate in treating the medical and functional symptoms of the abdominal region in 3 patients with no need for umbilical transposition. The remaining 32 patients required a different procedure instead of only an infraumbilical panniculectomy. Among these 32 patients, 3 patients underwent panniculectomy with sacrifice of the umbilicus. Umbilical transposition following abdominal undermining was needed in the remaining 29 patients undergoing panniculectomy. Functional umbilical transposition was required to avoid unnatural displacement of the navel while treating chronic skin problems in the lower abdomen, or additional persistent skin problems around the navel or in the mid-abdomen, and to access the supraumbilical region, particularly for large ventral hernia repair during panniculectomy. Therefore, umbilical transposition in these cases was not aesthetic in nature but an integral part of achieving a functional surgical treatment.


Emancipatory Visions: Using Visual Methods to Coconstruct Knowledge with Older Adults.
This article calls for gerontologists to engage with visual methods in qualitative research as an innovative tool for community-engaged research that has potential to advance social justice in gerontology. Reflections about using visual methods from the intersectional standpoint of the authors, 3 younger women of color, are presented. In Working the Hyphen, J. Yeh shows how interpersonal dynamics are fundamental to visual methods and that attention to identity can provide new insights into aging while also reconstituting existing power dynamics that researchers must carefully consider. In Employing Elicitation Techniques With Experts, L. Reyes discusses how a colonial lens limits understandings of civic participation and erases contributions of Black, Indigenous, and People of Color (BIPOC) older adults, proposing that elicitation techniques offer opportunities for BIPOC older adults to contribute their expertise to the research process and dissemination of findings beyond an academic audience. In Pedagogy and Practicality, H. S. Versey describes promises and complexities of scaling visual methods on multiple levels-teaching future generations of researchers the philosophy and practice of photovoice; negotiating university and community relationships through a service-learning project; and navigating identity between herself, her students, and research participants. In sharing our self-narratives, we integrate reflexivity into the research process and challenge power dynamics in knowledge construction.


Novel pathogenic variants in GBE1 causing fetal akinesia deformation sequence and severe neuromuscular form of glycogen storage disease type IV.
Glycogen storage disease IV (GSD IV), caused by a defect in GBE1, is a clinically heterogeneous disorder. A classical hepatic form and a neuromuscular form have been described. The severe neuromuscular form presents as a fetal akinesia deformation sequence or a congenital subtype. We ascertained three unrelated families with fetuses/neonates who presented with fetal akinesia deformation sequence to our clinic for genetic counseling. We performed a detailed clinical evaluation, exome sequencing, and histopathology examination of two fetuses and two neonates from three unrelated families presenting with these perinatally lethal neuromuscular forms of GSD IV. Exome sequencing in the affected fetuses/neonates identified four novel pathogenic variants (c.1459G>T, c.144-1G>A, c.1680C>G, and c.1843G>C) in GBE1 (NM_000158). Histopathology examination of tissues from the affected fetuses/neonate was consistent with the diagnosis. Here, we add three more families with the severe perinatally lethal neuromuscular forms of GSD IV to the GBE1 mutation spectrum.


The contradictions between Canadian capitalist processes and youth mental health: implications for mental health promotion.
Understanding how socio-economic processes inter-relate with young people's mental health is important to inform the development of responsive mental health promotion initiatives. Thirty diverse Canadian young people were engaged within a process of social praxis, underpinned by a historical-dialectical ontological perspective, to explore the inter-relation among socio-economic processes and youth mental health and implications for mental health promotion initiatives. Findings show several inter-related contradictory processes within two overarching contradictory dynamics that Canadian youth are navigating as they seek to realize their mental health needs. The first overarching contradictory dynamic is between monetized, private, individualistic, profit-oriented economic processes and young people's need for resources, freedom and time, and inclusive social spaces to enable their mental health needs. Participants' descriptions of their approaches to seeking to realize their mental health needs in this context reflects a second inter-related overarching contradiction between communal and individual approaches to enabling young people's mental health needs. In this context, young people are oriented inward to meet their mental health needs at the individual and inter-personal level, despite the crucial role of socio-economic processes to enabling their mental health needs. Despite varied access to resources, all participants struggled to balance meeting their mental health needs. Implications of these findings entail the need to focus on promoting synergistic relations among young people and socio-economic processes whereby enabling universal access to resources for young people's survival, physical health and comfort is foundational to multi-level mental health promotion initiatives.


Enrichment and Detection of Circulating Tumor Cells and Other Rare Cell Populations by Microfluidic Filtration.
The current standard methods for isolating circulating tumor cells (CTCs) from blood involve EPCAM-based immunomagnetic approaches. A major disadvantage of these strategies is that CTCs with low EPCAM expression will be missed. Isolation by size using filter membranes circumvents the reliance on this cell surface marker, and can facilitate the capture not only of EPCAM-negative CTCs but other rare cells as well. These cells that are trapped on the filter membrane can be characterized by immunocytochemistry (ICC) , enumerated and profiled to elucidate their clinical significance. In this chapter, we discuss advances in filtration systems to capture rare cells as well as downstream ICC methods to detect and identify these cells. We highlight our recent clinical study demonstrating the feasibility of using a novel method consisting of automated microfluidic filtration and sequential ICC for detection and enumeration of CTCs, as well as circulating mesenchymal cells (CMCs), circulating endothelial cells (CECs), and putative circulating stem cells (CSCs). We hypothesize that simultaneous analysis of circulating rare cells in blood of cancer patients may lead to a better understanding of disease progression and development of resistance to therapy.


Design of Strain-Hardening Natural TRM Composites: Current Challenges and Future Research Paths.
This paper discusses the challenges in using natural fibers for the development of textile-reinforced mortar (TRM) composites with pseudo-strain-hardening and multiple cracking behavior. The particular characteristics of natural vegetal fibers are analyzed with reference to data from the literature. It is concluded that the efficient use of these fibers as composite reinforcement requires the development of treatment or impregnation protocols for overcoming durability issues, eliminating crimping effects in tensile response and imparting dimensional stability. Relevant experimental research on the synthesis and performance of natural TRMs is reviewed, showing that the fabrication of such systems is, at present, largely based on empirical rather than engineering design. In order to set a framework regarding the properties that the constituents of natural TRM must meet, a comparative analysis is performed against inorganic matrix composites comprising synthetic, mineral and metallic reinforcement. This highlights the need for selecting matrix materials compatible with natural fibers in terms of stiffness and strength. Furthermore, a rational methodology for the theoretical design of natural TRM composites is proposed. First-order analysis tools based on rule-of-mixtures and fracture mechanics concepts are considered. Based on the findings of this study, paths for future research are discussed.


Effects of antioxidant agents against cyclosporine-induced hepatotoxicity.
To investigate the potential protective antioxidant role of ursodeoxycholic acid (UDCA), melatonin, and allopurinol treatment in cyclosporine (CsA)-induced hepatotoxicity. Hepatotoxicity was established in Sprague-Dawley rats by daily administration of CsA. Treatment groups were additionally administered UDCA, melatonin, or allopurinol treatments. Rats that received no CsA and no treatments served as a control group. Liver samples from each group were examined by histopathologic analysis to determine the effects of CsA treatment on liver morphology. Biochemical assays were also used to determine the effect of CsA treatment on liver function, in the presence or absence of UDCA, melatonin, or allopurinol. CsA treatment induced hepatotoxicity, resulting in sinusoidal dilatation, congestion, infiltration, hydropic degeneration, and loss of glycogen storage in the liver. From a molecular perspective, the CsA treatment increased levels of malondialdehyde (MDA) levels, decreased levels of reduced glutathione and xanthine oxidase, and decreased activities of superoxide dismutase and catalase. The CsA treatment also resulted in decreased serum total antioxidant capacity, whereas alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin levels, and total oxidant status were increased. Treatment with UDCA, melatonin, or allopurinol reduced the CsA-induced histopathologic changes, as compared with CsA-treated samples. In addition, UDCA, melatonin, or allopurinol treatment mitigated the CsA-induced effects on glutathione and MDA levels, and on superoxide dismutase and catalase activities, as well as reduced the CsA-mediated perturbations in serum levels of total antioxidant capacity, total oxidant status, and alkaline phosphatase. UDCA, allopurinol, and melatonin may each help to protect against CsA-induced damage to liver tissues, possibly through effects on the antioxidant system.


Homograft tympanic membrane myringoplasty.
During a six-year period, homograft tympanic membranes have been used successfully for myringoplasty or tympanoplasty in 85% of 175 cases. This percentage is not as high as might be expected with fascia, and the homografts have not been as dependable in the wet, draining ear. However, the results do show that the homograft is an acceptable grafting material. The eardrums are not suggested as substitutes for fascia, but should be available for difficult cases. Their use is indicated in large or total defects to restore the natural anatomical conical shape of the eardrum, particularly in congenital atresia. The prime indication for their use is a missing malleus, and the malleus handle can be included within the transplant. The eardrum's rigid properties and the possibility of inclusion of ossicles make the homografts valuable in reconstruction of the old mastoid cavity.


A case of accordion phenomenon accompanied by severe transmural myocardial ischemia.
Percutaneous coronary intervention was performed in a severely tortuous right coronary artery (RCA). Immediately after straightening its tortuousity by using two guidewires, angiographic slow flow, ischemic electrocardiographic changes, and anginal pain developed. This is a rare case who had severe myocardial ischemia caused by the accordion phenomenon.


Daily variability of acid-base status and determinants of serum bicarbonate in hemodialysis patients.
We aimed to evaluate daily variability of bicarbonate in hemodialysis (HD) patients and identify the factors which affect that issue. Blood samples of 41 patients for bicarbonate (total carbon dioxide (CO2)) and blood gas analysis (pH, bicarbonate (HCO3-)) were obtained, pre-dialysis and post-dialysis, on the first, second, and third session of the week. Those with pre-dialysis HCO3- < 22 mmol/L in all sessions were classified as acidotic. Demographic and laboratory data of acidotic and non-acidotic groups were compared, and the factors related to HCO3- level were identified. pH, tCO2, HCO3- of the first HD session were significantly lower than those of short inter-dialytic intervals (p < 0.001, respectively). Using Blant Altman analysis, pre- and post-dialysis tCO2 did not show good agreement with HCO3-. Acidotic patients had higher levels of serum albumin and phosphorus (p < 0.01 and p = 0.02, respectively) and were more likely to use sevelamer (p = 0.04). Also, the value of HCO3- was inversely correlated with dialysis vintage (r = -0.432, p = 0.005) and serum albumin (r = -0.427, p = 0.005). Since tCO2 did not show good agreement with HCO3-, relying solely on the pre-dialysis tCO2 values to define metabolic acidosis may increase misclassification rate. More work is needed for optimal assessment of acid-base status. Also, understanding the determinants of HCO3- may guide physicians for individualized HCO3- prescription.


Promoting physical activity within breast cancer survivors using behavior change techniques: N-of-1 randomized controlled trials.
Survivors of breast cancer are an important target for health promotion interventions, and physical activity (PA) is recommended with benefits being well established. More and more behavior theory guided interventions are planned and tailored to the individuals, targeting specifics needs and personal characteristics. We aimed to test the effectiveness of two behavior change techniques [coping planning (CP) and self-monitoring (SM)] for promoting PA in survivors of breast cancer, using a single-case design. In a powerful multiple sample N-of-1 RCT, 10 women post-breast cancer (M = 52.8 years) were randomly assigned to four experimental conditions (CP and/or SM, control) for 60 days and their daily step count was observed. The overall effects were analyzed using multilevel time-series with random intercepts. Time-series regression models and supplementary pairwise analyses were conducted for individuals. Multilevel analyses showed significant effects of CP and SM. Single-case analyses showed that six participants walked significantly more on the intervention days, that combined interventions were effective for five participants, but two participants had better results with the other two conditions. Combined self-regulatory techniques were more effective in promoting PA however, individual variability should be considered in future studies with survivors of breast cancer. Retrospectively registered: https://osf.io/eakjy/?view_only=81bf3dc084a0410a8ea28265e0f3c360, 31-01-2023.(raise query).


Effects of Diesel engine exhaust on pulmonary alveolar macrophages.
The in vivo effects of inhalation of diesel engine exhaust (DEE) on pulmonary alveolar macrophages (PAM) was studied in 73 guinea pigs and 48 rats. Animals were exposed in individual cages in special chambers to 3 different dose levels of DEE expressed in terms of the concentation of soot or carbon particles (-P); 250, 1500, 6000 micrograms DEE-P/M3. Exposure durations for guinea pigs were 1 and 3 days, 1 and 2 weeks, 2, 4, 8 and 12 months while rats were exposed 1, 2, 4, 8 and 12 months. Age matched controls were similarly exposed concurrently to "clean" air. PAM obtained by bronchopulmonary lavage from exposed animals had viabilities comparable to controls. PAM diameters and relative surface areas increased 2--3 fold over controls and in relation to both the dose of DEE-P given and the exposure duration. Most of the in vivo exposed PAM had phagocytized DEE-P which did not appear to be cytotoxic and remained confined in phagosomes as discrete particles with diameters of 0.014--0.072 micrometer. Ability of PAM to adhere and spread on test surfaces was greater in the DEE-P sets than in controls. DEE-P containing PAM were still able to phagocytize latex particles when fed in vitro. However, such PAM had defective phagocytosis ability, and did not in the same time interval take up as much fluorescent latex as controls when studied by flow system technology. Absolute numbers of PAM in guinea pig lavages from exposures to 250 and 1500 microgram DEE-P/M3 for 2 months were not significantly changed over concurrent controls. Exudative leukocytes (eosinophils in guinea pigs and neutrophils in rats) appeared in the lavage in greater numbers as dose and duration of exposure increased. Another species difference was the appearance in DEE-P exposed guinea pig lavages of "reactive" monocytes.


Excessive daytime sleepiness and risk of occupational injuries in non-shift daytime workers.
Only a few studies have examined the possible association between excessive daytime sleepiness (EDS) and risk of occupational injuries, and most of them were based on self-reports. This study tested this association in daytime workers using injury data taken from organizational archives. A retrospective and prospective study. It covered injury occurrence during two years prior to a sleep disorder assessment/education procedure and injury occurrence in the following year. The workers were given the assessment results and, when applicable, a letter to the treating physician. Eight industrial plants. Lectures and discussions on sleep disorders, treatment, and implications to safety and quality of life were conducted with small groups who completed the sleep assessment questionnaire beforehand. The workers completed the sleep assessment questionnaire prior to the lecture/discussion. 532 non-shift daytime workers. N/A. A battery of questionnaires to assess EDS (by the Epworth Sleepiness Scale), suspected sleep disorders, sleep habits, and job and environmental conditions. Of the workers studied 22.6% had EDS. Most of those (96.3%) indicated that they had experienced this propensity for the past two years or more and 56% of them had experienced it for 10 years or more. Logistic regression analysis indicated that during the two-year period prior to the procedure, EDS was associated with an increased risk of sustaining a work injury (OR=2.23, 95% CI 1.30-3.81), even after controlling for possible confounders, including factory category, job and environmental conditions. In the year after the procedure, the injury rate decreased by one-third in the workers with EDS but remained unchanged in the workers without EDS. Consequently, the association between EDS and injury was no longer significant (OR=1.42, 95% CI 0.71-2.85). EDS is a prevalent phenomenon in non-shift daytime workers. Workers with EDS had over two-fold higher risk of sustaining an occupational injury. Providing workers with the assessment results and of the implications of EDS for safety may explain the decrease in occupational injuries upon follow-up. This decrease might have occurred either because of workers taking steps to reduce EDS and/or adopting safety behaviors.


Social Withdrawal (Hikikomori) Conditions in China: A Cross-Sectional Online Survey.
A form of pathological social withdrawal which is also called hikikomori has been proved its existence in China. But the prevalence and characteristics of hikikomori in China remain unknown. Past studies had investigated the hikikomori phenomenon in three cities of China. The purpose of this study is to discover the prevalence of hikikomori in a convenient online sample in China as well as the difference in demographic characteristics and other possible traits between hikikomori sufferers and the general population. A total of 1,066 youths (mean age = 22.85 years) in China completed the online questionnaire, which consisted of questions about demographics, the 25-item Hikikomori Questionnaire (HQ-25), the Internet Addiction Test (IAT), the Loneliness Scale (UCLA), and the General Health Questionnaire (GHQ). SPSS is used to evaluate the data. Of the 1,066 youths, 980 (91.9%) were identified as belonging to group A (be not social isolation nor withdrawn), 46 (4.3%) to group B (marked social isolation in one's home or withdrawn with a duration of at least 3 months), and 40 (3.8%) to group C (marked both social isolation in one's home and withdrawn with a duration of at least 3 months). The hikikomori group (combined group B and group C) accounted for 8.1%. The present data suggest that residence and loneliness are related to the occurrence of hikikomori. HQ-25 score of the hikikomori group was significantly higher than the comparison group. The UCLA score showed that those in the hikikomori group felt lonelier than those in the comparison. The regression model predicted hikikomori risk (χ2 = 38.658, P = 0.000), the Hosmer-Lemeshow test value is 7.114 and P = 0.524 > 0.05. The grouping criterion in our present study is reasonable and such a grouping criterion can screen out potential populations of hikikomori. When people develop into hikikomori sufferers in the present, their social withdrawal behaviors and feeling of loneliness are both much more severe than in the past. The possible relationships between hikikomori and loneliness reflect the need to give the youths more social support, to help them connect with society.


Volumetric MRI Changes in Spinocerebellar Ataxia (SCA3 and SCA10) Patients.
Spinocerebellar ataxias type 3 (SCA3) and type 10 (SCA10) are the most prevalent in southern Brazil. To analyze the relationships between volumetric MRI changes and clinical and genetic findings in SCA3 and SCA10 patients. All patients in the study had a confirmed genetic diagnosis. Demographic data, ataxia severity (SARA score), and the size of the expanded alleles were evaluated. Nineteen SCA3 and 18 SCA10 patients were selected and compared with a similar number of healthy controls. Patient and control groups underwent the same MRI protocol. The standard FreeSurfer pipeline was used for the morphometric data. Our results show more affected brain structures (volume reductions) in SCA3 patients than in SCA10 patients (15 vs. 5 structures). Volume reductions in brain structures were also greater in the former. The main areas with significant volumetric reductions in the former were the cerebellum, basal ganglia, brain stem, and diencephalon, whereas in the latter, significant volume reductions were observed in the cerebellum and pallidum. While SARA scores and disease duration were more correlated with volume reduction in SCA10, in SCA3, the expansion length (CAGn) correlated positively with cerebellar WM, thalamus, brain stem, and total GM volumes. There was no correlation between expansion length (ATTCTn) and neuroimaging findings in SCA10. Neuroimaging results differed significantly between SCA3 and SCA10 patients and were compatible with the differences in clinical presentation, disease progression, and molecular findings.


Proctoscopy following transrectal prostate biopsy can control rectal bleeding after prostate biopsy.
Rectal bleeding is a common complication of transrectal ultrasound-guided prostate biopsy (TRPB). Massive rectal bleeding after TRPB can be life threatening. We initiated proctoscopy after TRPB to clarify the incidence of rectal bleeding and evaluated the usefulness of proctoscopy for controlling bleeding after TRPB. Two hundred and fifty six patients who underwent TRPB were included in the study. TRPB was performed under local anesthesia. Post-biopsy, we performed a proctoscopy to evaluate the degree of rectal bleeding at four levels (G0, no bleeding; G1, traces; G2, venous bleeding requiring hemostasis; and G3, massive venous bleeding or arterial bleeding). Once the bleeding site on the rectal wall was identified, a gauze tampon was placed at the bleeding site and compressed for a few minutes. A second proctoscopy was performed to confirm complete hemostasis, after which the TRPB was terminated. Proctoscopy revealed that the degree of bleeding was G0 in 27 cases, G1 in 104 cases, G2 in 116 cases, and G3 in nine cases. Rectal bleeding that required hemostasis (G2 and G3) was observed in 125 of 256 cases (48.3%). Among the 125 cases, bleeding was stopped by compression in 121 cases; in the remaining four cases, bleeding continued despite compression and was stopped by suturing of the bleeding site. Suturing was performed by urologists, and none of the 256 patients had problematic posterior hemorrhage. Proctoscopy enables precise and effective pressure hemostasis. Moreover, suturing hemostasis under direct vision can be performed in cases in which pressure hemostasis is difficult. Continued proctoscopy allays urologists' fear of post-TRPB rectal bleeding.


Prosthetic stimulation of the auditory system with intraneural electrodes.
Prosthetic electrical stimulation of the auditory system is presently accomplished either via scala tympani electrode arrays or via cochlear nucleus surface electrode arrays. Many of the early cochlear implant studies, however, used electrode arrays placed within the auditory nerve itself--either within the modiolus or within the trunk of the nerve. For many reasons, such intraneural electrode arrays were abandoned in favor of intrascalar arrays. There remain, however, several theoretical and practical reasons why intraneural arrays might be advantageous, and recent developments in electrode technology solve many of the problems posed by early attempts at intraneural stimulation. In this article, we review the history and current status of intraneural auditory stimulation, and present some preliminary results of this mode of stimulation in an animal model.


CD74: a new candidate target for the immunotherapy of B-cell neoplasms.
CD74 is an integral membrane protein that functions as a MHC class II chaperone. Moreover, it has recently been shown to have a role as an accessory-signaling molecule and has been implicated in malignant B-cell proliferation and survival. These biological functions combined with expression of CD74 on malignant B cells and limited expression on normal tissues implicate CD74 as a potential therapeutic target. The anti-CD74 monoclonal antibody LL1 has been humanized (hLL1 milatuzumab or IMMU-115) and can provide the basis for novel therapeutic approaches to B-cell malignancies, particularly because this antibody shows rapid internalization into CD74+ malignant cells. This article reviews the preclinical evaluations of LL1, its humanized form, and isotope, drug, and toxin conjugates. These studies show that unconjugated hLL1 and conjugates of hLL1 constructs with radioisotopes, doxorubicin, and frog RNase have high antitumor activity in non-Hodgkin's lymphoma and multiple myeloma in vitro and in tumor xenograft models. Single-dose studies of hLL1 in monkeys showed no adverse effects but did decrease circulating B and T lymphocytes and natural killer cells. When evaluated in combination with rituximab, either equivalent or improved efficacy, compared with either antibody alone, was observed. CD74 is a new candidate target for the immunotherapy of neoplasms expressing this antigen, which can be exploited using either a naked antibody or conjugated to isotopes, drugs, or toxins.


Primary nocturnal enuresis in children. Background and treatment.
The aim of the present studies was to investigate background factors and treatment in children with monosymptomatic primary nocturnal enuresis. The study material comprised enuretics, former enuretics and controls from the municipal community of Falkenberg on the west coast of Sweden. Whenever possible all investigations were made with the children staying in their own home environment. Different background factors have been suspected as being causative: sleep disturbances, behavioural or psychological disturbances, small bladder capacity, increased night diuresis and an insufficient production of the antidiuretic hormone during sleep. These factors have been investigated in these studies. The treatment of enuresis has been dominated by the alarm and antidiuretic treatment with DDAVP. Primary nocturnal monosymptomatic enuresis is a common problem in childhood. In this study the prevalence among 392 seven year old children was 7.3%. A prior history of enuresis was found in 65% of families of the enuretics compared to 25% in controls. The enuretic children showed no statistically significant differences in behavioural or psychological problems compared to non-enuretic children. Enuretic children were described as heavy sleepers by their parents and a wake-up test performed at home showed that they were statistically significantly harder to arouse than the controls. Children with nocturnal enuresis, former enuretics and controls did not differ in social or behavioural traits in an interview study. No signs of symptom substitution was found when enuresis was resolved. Enuretic children had a normal bladder capacity and no statistically significant difference was found compared to controls and former enuretics. The enuretic children showed a normal calcium-creatinine quota in the urine. Former enuretic children showed a significantly enhanced calcium/creatinine quota compared to enuretics and controls. Enuretic children had a statistically significant lower morning plasma level of the anti diuretic hormone vasopressin than non-enuretic children. Enuretic children were treated for 12 weeks with DDAVP or the alarm. DDAVP treated patients had a more rapid effect compared with alarm treated patients. Alarm treated children had a lower relapse frequency. Enuretic children were treated in a randomised, double blind, double dummy, cross over, placebo-controlled study with DDAVP 20 micrograms intranasally by a single dose pipette or 200 micrograms orally as a tablet. Both methods were equally effective in controlling enuresis, but significantly superior to placebo. Enuretic children are normal, well adjusted children with a normal bladder capacity, a high level of arousal threshold, and a low morning level of plasma vasopressin. The alarm and DDAVP are equally effective in treating enuresis.(ABSTRACT TRUNCATED AT 400 WORDS)


Aluminum Enhances Growth and Sugar Concentration, Alters Macronutrient Status and Regulates the Expression of NAC Transcription Factors in Rice.
Aluminum (Al) is a beneficial element for some plant species, especially when used at low concentrations. Though some transcription factors are induced by exposure to this element, no data indicate that Al regulates the expression of NAC genes in rice. In this study we tested the effect of applying 200 μM Al on growth, chlorophyll, amino acids, sugars, macronutrient concentration and regulation of NAC transcription factors gene expression in 24-day-old plants of four rice (Oryza sativa ssp. indica) cultivars: Cotaxtla, Tres Ríos, Huimanguillo and Temporalero, grown hydroponically under greenhouse conditions. Twenty days after treatment, we observed that Al enhanced growth in the four cultivars studied. On average, plants grown in the presence of Al produced 140% more root dry biomass and were 30% taller than control plants. Cotaxtla and Temporalero showed double the root length, while Huimanguillo and Cotaxtla had three times more root fresh biomass and 2.5 times more root dry biomass. Huimanguillo plants showed 1.5 times more shoot height, while Cotaxtla had almost double the root dry biomass. With the exception of Tres Ríos, the rest of the cultivars had almost double the chlorophyll concentration when treated with Al, whereas amino acid and proline concentrations were not affected by Al. Sugar concentration was also increased in plants treated with Al, almost 11-fold in comparison to the control. Furthermore, we observed a synergic response of Al application on P and K concentration in roots, and on Mg concentration in shoots. Twenty-four hours after Al treatment, NAC transcription factors gene expression was measured in roots by quantitative RT-PCR. Of the 57 NAC transcription factors genes primer-pairs tested, we could distinguish that 44% (25 genes) showed different expression patterns among rice cultivars, with most of the genes induced in Cotaxtla and Temporalero plants. Of the 25 transcription factors up-regulated, those showing differential expression mostly belonged to the NAM subfamily (56%). We conclude that Al improves growth, increases sugar concentration, P and K concentrations in roots, and Mg concentration in shoots, and report, for the first time, that Al differentially regulates the expression of NAC transcription factors in rice.


β5 integrin up-regulation in brain-derived neurotrophic factor promotes cell motility in human chondrosarcoma.
Chondrosarcoma is a primary malignant bone cancer, with a potent capacity to invade locally and cause distant metastasis; it has a poor prognosis and shows a predilection for metastasis to the lungs. Brain derived neurotrophic factor (BDNF) is a small-molecule protein from the neurotrophin family of growth factors that is associated with the disease status and outcomes of cancers. However, the effect of BDNF on migration activity in human chondrosarcoma cells is mostly unknown. Here, we found that human chondrosarcoma tissues showed significant expression of BDNF, which was higher than that in normal cartilage and primary chondrocytes. We also found that BDNF increased the migration and expression of β5 integrin in human chondrosarcoma cells. In addition, knockdown of BDNF expression markedly inhibited migratory activity. BDNF-mediated migration and β5 integrin up-regulation were attenuated by antibody, inhibitor, or siRNA against the TrkB receptor. Pretreatment of chondrosarcoma cells with PI3K, Akt, and NF-κB inhibitors or mutants also abolished BDNF-promoted migration and integrin expression. The PI3K, Akt, and NF-κB signaling pathway was activated after BDNF treatment. Taken together, our results indicate that BDNF enhances the migration of chondrosarcoma by increasing β5 integrin expression through a signal transduction pathway that involves the TrkB receptor, PI3K, Akt, and NF-κB. BDNF thus represents a promising new target for treating chondrosarcoma metastasis.


Long-term influence of perinatal asphyxia on the social behavior in aging rats.
Various groups have been addressing the question of whether perinatal asphyxia (PA) affects the behavior of young animals, but no information is available on long-term effects of PA on the behavior in aged rats, although it has been postulated that PA may lead to neurological and psychiatric deficits in adult life. We, therefore, decided to study the effects of PA on social and anxiety-related behaviors in 2-year-old rats, using a noninvasive animal model resembling the clinical situation. For the behavioral studies, the open-field test, the elevated plus-maze test, and a social interaction test in pairs were performed. Magnetic resonance imaging of the brain was selected to rule out neuropathological changes due to the aging process per se, as well as asphyxia-induced pathologies in the brain areas known to play an important role in the modulation of behavior. The social interaction test revealed a statistically significant increase in the number of social grooming episodes and the time spent running alone, whereas the numbers of social sniffing and fighting episodes and the time spent running together were decreased in the asphyxiated group. The elevated plus- maze test revealed a higher presence of entries into the closed arm. Furthermore, sniffing and self-grooming episodes were significantly increased in the asphyxiated group. We found a significantly decreased social aggressiveness and an increased social contact behavior as well as increased anxiety levels in the asphyxiated animals. The present findings may provide important information on the long-term behavioral sequelae of PA in the aged individual.


Platelet testing in flow diversion: a review of the evidence.
OBJECTIVE Although the use of dual antiplatelet therapy with flow diversion is recommended and commonplace, the testing of platelet inhibition is more controversial. METHODS The authors reviewed the medical literature to establish and describe the physiology of platelet adhesion, the pharmacology of antiplatelet medications, and the mechanisms of the available platelet function tests. Additionally, they present a review of the pertinent neurointerventional and interventional cardiology literature. RESULTS Competing reports in the neurointerventional literature argue for and against the use of routine platelet function testing, with adjustments to the dosage or medications based on the results. The interventional cardiology literature has also wrestled with this dilemma after percutaneous coronary interventions, with conflicting reports of the benefits of platelet function testing. CONCLUSIONS Despite its prevalence, the benefits of platelet function testing prior to flow diversion are unproven. This practice will likely remain controversial until the level of evidence improves through more rigorous testing and reporting.


Charge transport in molecular electronic junctions: compression of the molecular tunnel barrier in the strong coupling regime.
Molecular junctions are essentially modified electrodes familiar to electrochemists where the electrolyte is replaced by a conducting "contact." It is generally hypothesized that changing molecular structure will alter system energy levels leading to a change in the transport barrier. Here, we show the conductance of seven different aromatic molecules covalently bonded to carbon implies a modest range (< 0.5 eV) in the observed transport barrier despite widely different free molecule HOMO energies (> 2 eV range). These results are explained by considering the effect of bonding the molecule to the substrate. Upon bonding, electronic inductive effects modulate the energy levels of the system resulting in compression of the tunneling barrier. Modification of the molecule with donating or withdrawing groups modulate the molecular orbital energies and the contact energy level resulting in a leveling effect that compresses the tunneling barrier into a range much smaller than expected. Whereas the value of the tunneling barrier can be varied by using a different class of molecules (alkanes), using only aromatic structures results in a similar equilibrium value for the tunnel barrier for different structures resulting from partial charge transfer between the molecular layer and the substrate. Thus, the system does not obey the Schottky-Mott limit, and the interaction between the molecular layer and the substrate acts to influence the energy level alignment. These results indicate that the entire system must be considered to determine the impact of a variety of electronic factors that act to determine the tunnel barrier.


Quantitation of carcinogen-induced DNA damage and repair in human cells with the UVR ABC excision nuclease from Escherichia coli.
Recent studies by others have shown that the endonuclease complex coded for by the uvrA, uvrB and uvrC genes of Escherichia coli (UVR ABC excision nuclease) can incise DNA containing a variety of 'bulk-type' lesions, such as those resulting from u.v. light, (+/-)-7 alpha,8 beta-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE), and N-acetoxy-2-acetylaminofluorene. Using partially purified UVR ABC excision nuclease, we have quantitated the number of endonuclease sensitive sites (ESS) in purified DNA isolated from human fibroblasts treated with u.v. light or BPDE. The number of ESS/10(8) daltons of DNA were calculated from the number average mol. wt. of the DNA as determined by sedimentation in alkaline sucrose gradients. The number of endonuclease sites increased linearly with increasing doses of either u.v. light or BPDE. The UVR ABC excision nuclease was able to incise a majority of the BPDE-DNA adducts. Xeroderma pigmentosum fibroblasts, complementation group A (XP12BE) had 20-25% more ESS at each dose than the BPDE-treated normal (HSBP) cells. Cells treated with 4 microM BPDE and allowed 12 h of incubation to perform excision repair showed removal of 60% of the initial number of ESS from HSBP DNA and 40% of the ESS from XP-A DNA. Beyond 12 h XP12BE cells lost no additional ESS while HSBP cells continued to lose ESS, although at a slower rate, until at 48 h only 22% of the initial ESS remained. In cells treated with 10 J/m2 of u.v. light, the UVR ABC excision nuclease detected 60% of the sites recognized by the pyridimine dimer specific Micrococcus luteus glycosylase/apyrimidinic endonuclease. These results demonstrate the potential use of the UVR ABC excision nuclease in a quantitative assay for determining the number of carcinogen-induced lesions in human DNA.


Clinical application of the probenecid test for measurement of monoamine turnover in the CNS.
The probenecid-induced accumulation of the acidic metabolites of dopamine and serotonin is widely used to estimate the CNS turnover of these amines in human subjects. The theoretical basis of the probenecid test is discussed, including the assumptions on which the test is based, and the limitations of the procedure. Suggestions are offered on appropriate methods for analyzing test data. Available evidence suggests that maximal inhibition of the efflux of the acidic metabolites of dopamine and serotonin from the CSF is not achieved with probenecid doses up to 100 mg/kg. Therefore, before a comparison can be made between the accumulation of CSF metabolites from different groups of subjects, a correction for CSF probenecid concentrations is necessary. Moreover, in addition to the measurement of dopamine and serotonin turnover, the probenecid test can be extended to include comparisons of CNS turnover of other monoamines including octopamine, p-tyramine, and tryptamine.


[Construction of the recombinant adenovirus vector carrying antisense multidrug resistance (MDR1) gene].
The fragment of MDR1 gene obtained from the plasmid pHaMDR1-1 carrying the whole human MDR1 cDNA, was cloned reversely into the shuttle plasmid pAdTrack-CMV. With the resultant plasmid and the backbone plasmid pAdEasy-1, the homologous recombination took place in the Escherichia coli BJ5183 and the recombinant adenoviral plasmid was generated. The adenoviruses were packaged in the 293 cells. The recombinant adenovirus MDR1 vector would introduce the antisense MDR1 gene into the human multidrug resistance hepatocellular cell line effectively, which would provide an experimental basis for studies on the multidrug resistance in human hepatocellular carcinoma.


Workplace Empowerment and Job Satisfaction in Portuguese Nurses: An Explicative Model.
Greater effectiveness of health care does occur with a more effective management of interpersonal processes. A working management environment, which ensures sufficient access to information, support, resources, and opportunities (structural empowerment), probably can promote a personal perception of capacity and effectiveness (global empowerment) in caregivers to achieve organizational objectives and job satisfaction. This study evaluated the relationship between empowerment and job satisfaction, supported by Kanter's theory of structural empowerment. This study used a convenience sample of 151 nurses from public Portuguese hospitals. The adjustment of the model and the effect of mediation were carried out with a structural equation model (path analysis) through the statistical software STATA. The results show the mediator effect of global empowerment on the relationship between structural empowerment and job satisfaction and the direct and indirect effects of "access to opportunities" in job satisfaction. Managers of these health units should consider that the more the work environment is characterized by having the resources, opportunities, and support indispensable to the good execution of the work by the nurses, the greater the global empowerment and job satisfaction. The results obtained can be an important contribution that can be adopted as a strategy in any health institution without any harm.


Lipoinjection as a treatment of pacemaker pocket neuralgia.
Chronic severe pacemaker pocket neuralgia secondary to inadequate subcutaneous tissue between the pacemaker and overlying skin typically is treated by surgical pocket revision or relocation of the system. A case of this complication successfully treated by lipoinjection is reported. Additional experience is needed to confirm the usefulness of the technique as a means of providing symptomatic relief without the risks associated with more invasive procedures.


Statewide Implementation of Universal Third-Trimester Repeat HIV Testing in Illinois.
This article aims to assess statewide uptake of HIV repeat testing in the first 2 years after the implementation of an amendment to the Illinois Perinatal HIV Prevention Act (IPHPA) mandating universal repeat HIV testing in the third trimester. This is a retrospective, population-based study of all birthing individuals in Illinois (2018-2019). Data were collected using the state-mandated closed system of perinatal HIV test reporting. We evaluated the incidence of mother-infant pairs with negative early tests and repeat third-trimester tests (RTTTs) performed in adherence with the law, as well as the timing of the performance of the RTTTs (outpatient vs. inpatient). Chi-square tests of trend by quarter were performed to ascertain sustainability. Of 138,805 individuals delivered in 2018, 80.6% presented with early test and RTTTs. In 2018, outpatient RTTTs improved from 71.8% (quarter 1) to 85.1% (quarter 4; p < 0.001). In 2018, the proportion of mother-infant dyads who received testing that was adherent to the IPHPA Amendment was 92.1, 95.5, 96.7, and 96.4% in quarters 1 through 4, respectively (p < 0.001). In 2019, outpatient RTTTs performance remained high (87.4%) and stable (p = 0.06). In 2019, 99.9% of mother-infant dyads had testing adherent to the mandate in quarters 1 through 4 (p = 0.39). Of individuals who presented without RTTTs, 93.5% (2018) and 98.8% (2019) underwent inpatient testing before delivery. Implementation of RTTTs in Illinois was rapid, successful, and sustained in its first 2 years. Public health methodologies from Illinois may benefit other states implementing RTTT programs. · In 2018, Illinois enacted statewide RTTT for HIV among all parturients.. · In 2019, over 99% of mother-infant dyads had documentation of both early and repeat HIV testing before hospital discharge.. · Implementation of repeat third-trimester HIV testing in Illinois was rapid, successful, and sustained in its first 2 years.. · Public health methodologies from Illinois may benefit other states implementing similar programs..


Divergent properties of prolamins in wheat and maize.
Cereal grains are an important nutritional source of amino acids for humans and livestock worldwide. Wheat, barley, and oats belong to a different subfamily of the grasses than rice and in addition to maize, millets, sugarcane, and sorghum. All their seeds, however, are largely devoid of free amino acids because they are stored during dormancy in specialized storage proteins. Prolamins, the major class of storage proteins in cereals with preponderance of proline and glutamine, are synthesized at the endoplasmic reticulum during seed development and deposited into subcellular structures of the immature endosperm, the protein bodies. Prolamins have diverged during the evolution of the grass family in their structure and their properties. Here, we used the expression of wheat glutenin-Dx5 in maize to examine its interaction with maize prolamins during endosperm development. Ectopic expression of Dx5 alters protein body morphology in a way that resembles non-vitreous kernel phenotypes, although Dx5 alone does not cause an opaque phenotype. However, if we lower the amount of γ-zeins in Dx5 maize through RNAi, a non-vitreous phenotype emerges and the deformation on the surface of protein bodies is enhanced, indicating that Dx5 requires γ-zeins for its proper subcellular organization in maize.


Crystal-engineering studies of coordination polymers and a molecular-looped complex containing dipyridyl-amide ligands.
We report herein crystal-engineering studies of coordination polymers and a molecular-looped complex containing two dipyridyl-amide ligands, 1,3-bis-pyridin-4-ylmethyl urea (L1) and N,N'-bis-4-methylpyridyl oxalamide (L2). The reaction of Cd(OAc)2 with L1 gives rise to [Cd(OAc)2(L1)]n (1), a 1-D chain through coordination to two L1 and two acetate ligands, and then the axial coordination to one urea's carbonyl group through the third L1 ligand leads 1 to form "a dimer of 1-D chains". With a slight change in the structural backbone from L1 to L2, the reaction of L2 with Cd(OAc)2 gives [Cd(OAc)2(L2)(H2O)]n (2), a 1-D chain structure. The reaction of Cd(NO3)2, instead of Cd(OAc)2, with L2 gives [Cd(NO3)2(L2)3/2]n (3), where the coordinated-anion effect on the assembly process has been observed for 2 and 3. The former forms a 1-D chain structure, and the latter, a 2-D sheet structure, depending on the coordinated anions used. [HgCl2(L1)]n (4) and [CuCl2(L2)]n (5), which are 1-D chain structures, show tetrahedral [Hg(II)] and square-planar [Cu(II)] centers, respectively. Surprisingly, 4 shows a typical amide-amide hydrogen bonding and 5 shows none. Instead, a hydrogen-bonding interaction between Cl and the amide group is observed in 5. Finally, the different structural conformation of L2 (a syn or anti form) leads to the formation of different structural motifs, coordination polymers (2, 3, and 5 with an anti form), and a macrocycle ([Pd(PPy)(L2)]2(ClO4)2 (6) with a syn form, PPy = 2-phenylpyridine). Each side of the boat form of 6 (pseudo-cyclohexane) ranges from 6.12 to 6.39 A, and the molecular loop is further hydrogen-bonded to stack into a 1-D hydrogen-bonded framework with a ladder pattern through amide-amide hydrogen bonding. Interestingly, one ClO4- anion is encapsulated inside the cavity through multiple CH...O interactions.


'Neighbour smoke'--exposure to secondhand smoke in multiunit dwellings in Denmark in 2010: a cross-sectional study.
'Neighbour smoke' is transfer of secondhand smoke between apartments including shared areas, such as hallways, community rooms and stairwells in multiunit dwellings and is an emerging issue for public health and health equity. To describe the prevalence of exposure to neighbour smoke in Denmark. A population-based sample of 5049 respondents (2183 in multiunit dwellings) living in Denmark aged ≥15 years completed a questionnaire in 2010 on tobacco-related behaviour and exposure to secondhand smoke. The authors examined the relations between exposure to neighbour smoke, own smoking, smoking inside the home, type of residence and demographic factors with descriptive statistics and logistic regression analysis. In this sample, 22% of those living in multiunit dwellings reported exposure to neighbour smoke. Of respondents living in apartments, 41% preferred to live in a building in which smoking is banned. Smoke-free buildings were preferred by 58% of persons exposed to neighbour smoke compared with 37% of persons not exposed. Of the smokers (daily and occasional), 14% preferred to live in a smoke-free building; 31% never smoked indoors in their own home. The only way to avoid absorbing tobacco smoke from neighbours is to live in a smoke-free multiunit dwelling. There is great demand for such dwellings, especially by young people, people with children and people exposed to neighbour smoke, as well as by people who smoke.


Pharmacokinetics of (+)-, (-)- and (+/-)-verapamil after intravenous administration.
The pharmacokinetics of (+)-, (-)-, and (+/-)-verapamil were studied in five healthy volunteers following i.v. administration of the drugs. Pronounced differences of the various pharmacokinetic parameters were observed between the (-)- and (+)-isomers. The values for CL, V, Vz, and Vss of the (-)-isomer were substantially higher as compared to the (+)-isomer, whereas terminal t 1/ 2Z was nearly identical for both isomers. No dose dependency of the pharmacokinetics could be observed in two subjects who received 5, 7.5 and 10 mg of (-)- and 5, 25 and 50 mg of (+)-verapamil. Protein binding for the two isomers was also different. The fu of (-)- (0.11) was almost twice as much as that of (+)-verapamil (0.064). Pharmacokinetic parameters of (+/-)-verapamil, which was administered to three subjects who had received (+)- and (-)-verapamil, were very similar to the averaged values of the isomers given separately. Due to the higher CL of (-)-verapamil the extraction ratio of the (-)-isomer is substantially higher. Thus, it can be anticipated that following oral administration of racemic verapamil bioavailability of (-)-verapamil will be substantially less. Since the (-)-isomer is more potent than the (+)-isomer, the present findings could explain the reported differences in the concentration-effect relationship after i.v. and oral administration of racemic verapamil.


Nutritional strategies of high level natural bodybuilders during competition preparation.
Competitive bodybuilders employ a combination of resistance training, cardiovascular exercise, calorie reduction, supplementation regimes and peaking strategies in order to lose fat mass and maintain fat free mass. Although recommendations exist for contest preparation, applied research is limited and data on the contest preparation regimes of bodybuilders are restricted to case studies or small cohorts. Moreover, the influence of different nutritional strategies on competitive outcome is unknown. Fifty-one competitors (35 male and 16 female) volunteered to take part in this project. The British Natural Bodybuilding Federation (BNBF) runs an annual national competition for high level bodybuilders; competitors must qualify by winning at a qualifying events or may be invited at the judge's discretion. Competitors are subject to stringent drug testing and have to undergo a polygraph test. Study of this cohort provides an opportunity to examine the dietary practices of high level natural bodybuilders. We report the results of a cross-sectional study of bodybuilders competing at the BNBF finals. Volunteers completed a 34-item questionnaire assessing diet at three time points. At each time point participants recorded food intake over a 24-h period in grams and/or portions. Competitors were categorised according to contest placing. A "placed" competitor finished in the top 5, and a "Non-placed" (DNP) competitor finished outside the top 5. Nutrient analysis was performed using Nutritics software. Repeated measures ANOVA and effect sizes (Cohen's d) were used to test if nutrient intake changed over time and if placing was associated with intake. Mean preparation time for a competitor was 22 ± 9 weeks. Nutrient intake of bodybuilders reflected a high-protein, high-carbohydrate, low-fat diet. Total carbohydrate, protein and fat intakes decreased over time in both male and female cohorts (P < 0.05). Placed male competitors had a greater carbohydrate intake at the start of contest preparation (5.1 vs 3.7 g/kg BW) than DNP competitors (d = 1.02, 95% CI [0.22, 1.80]). Greater carbohydrate intake in the placed competitors could theoretically have contributed towards greater maintenance of muscle mass during competition preparation compared to DNP competitors. These findings require corroboration, but will likely be of interest to bodybuilders and coaches.


Hematopoietic Stem Cell Transplantation: A Neonatal Perspective.
Allogeneic hematopoietic stem cell transplantation (HSCT) is indicated in various nonmalignant disorders that arise from genetic, hematopoietic, and immune system defects. Many of the disorders described here have life-threatening consequences in the absence of HSCT, a curative intervention. However, timing and approach to HSCT vary by disorder and optimum results are achieved by performing transplantation before irreversible disease-related morbidity or infectious complications. This article details the principles of HSCT in the very young, lists indications, and explores the factors that contribute to successful outcomes based on transplantation and disease-related nuances. It provides an overview into the HSCT realm from a neonatologist's perspective, describes the current status of transplantation for relevant disorders of infancy, and provides a glimpse into future efforts at improving on current success.


Effects of Crest Whitestrips bleaching on subsurface microhardness and ultrastructure of tooth enamel and coronal dentin.
To describe the complementary subsurface analysis of structural and ultrastructural effects of bleaching with Crest Whitestrips on enamel and coronal dentin Human tooth enamel specimens were cycled through a daily regimen including salivary immersions and treatments with commercial tooth whitening gels containing hydrogen peroxide or carbamide peroxide. Treatments with hydrogen peroxide in Crest Whitestrips gel base were carried out for up to 70 hours bleaching (some five fold to the clinical exposure required to produce satisfactory whitening in bleaching strip systems as established by double blind placebo controlled clinical studies) [correction]. Following in vitro laboratory cycling, the teeth were cross sectioned and remounted for observation of microhardness and ultrastructural characteristics in subsurface regions. Ultrastructure was assessed by application of confocal laser scanning microscopy (reflection mode). Peroxide whitening compositions had no effects on subsurface microhardness of enamel or dentin, even under conditions of five fold overbleaching. Crest Whitestrips gel containing up to 6.5% hydrogen peroxide applied for periods up to 70 hours (five kit) overbleaching was found to produce no changes (at a lateral resolution of 200-300 nm) in observed subsurface enamel and dentin ultrastructure or architecture.


Can We Routinely Employ the Use of Low-Pressure Gynaecological Laparoscopy? A Systematic Review.
Clinicians have learnt valuable lessons throughout the COV-SARS-2 pandemic, many of which have produced solutions that we aim to continue to implement within the foreseeable future. Optimising patients' surgical pathways to reduce the length of stay and complications is an area of particular importance, both for maximal utilisation of available resources and for reduction of the exposure of inpatient and elective patients to an increased risk of infection within healthcare facilities. The aim of this review was to investigate the possible implications of using low-pressure laparoscopic gynaecological surgery versus standard- or high-pressure pneumoperitoneum surgeries. The primary outcome was postoperative pain, with secondary outcomes including duration of surgery, length of inpatient stay and rate of complications. MEDLINE, Embase and Cochrane CENTRAL were searched from inception to December 2020. We searched for published randomised control trials comparing low-pressure laparoscopic surgery (≤8 mmHg) to at least one additional standardised pneumoperitoneum pressure (≥12 mmHg and/or ≥15 mmHg). A total of 203 studies were reviewed, five of which were included in this analysis. Studies comparing low-pressure laparoscopic surgery against gasless abdominal cavities were excluded. The meta-analysis of the results was pooled and calculated within RevMan 5.0 software (Cochrane, London, England). Studies using a visual analogue scale (1-10) to compare low versus standard pneumoperitoneum pressures did not display a significant diminution of postoperative pain at ≤ 6 or 24 hours: -0.30 [95% CI -0.63, 0.03] and -0.66 [95% CI -1.35, 0.02], respectively. Studies additionally demonstrated worse visualisation of the surgical field within the low-pressure group (risk ratio 10.31; 95% CI, 1.29-82.38 I2 = 0%). Studies measuring postoperative pain using a numerical rating scale displayed significant pain reduction at all hours measured (p ≤ 0.01). The rate of intraoperative complications was 1% for all groups measured. Cumulative analysis of the duration of surgery did not differ significantly between groups (p = 0.99). The pandemic has revealed new issues that must be addressed by clinicians to promote the safety of patients and the efficiency of inpatient stay. This review has paved the way for new possibilities and innovative approaches to address the issue of optimising patient surgical pathways; however, at present, we cannot give a firm justification for the use of low-pressure gynaecological laparoscopy. Reasons for this include the minimal reduction in pain scores between low, standard and high pneumoperitoneum pressures, leading to a mixture of statistically significant results, as well as a reduction in the visualisation of the surgical field and the small population sizes in the reviewed papers. Additional research is required to further explore the potential clinical benefits of gynaecological laparoscopy to ensure its effective ambulatory use within mainstream surgical operations.


Hybridization Chain Reactions Targeting the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).
In this work, hybridization chain reactions (HCRs) toward Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) nucleocapsid phosphoproteins gene loci and human RNase P are proposed to provide an isothermal amplification screening tool. The proposed chain reactions target the complementary DNA (cDNA) of SARS-CoV-2, with loci corresponding to gold-standard polymerase chain reaction (PCR) loci. Four hybridization chain reaction reactions are demonstrated herein, targeting N1/N2/N3 loci and human RNase P. The design of the hybridization chain reaction, herein, is assisted with an algorithm. The algorithm helps to search target sequences with low local secondary structure and high hybridization efficiency. The loop domain of the fuel hairpin molecule H1 and H2, which are the tunable segments in such reactions, are used as an optimization parameter to improve the hybridization efficiency of the chain reaction. The algorithm-derived HCR reactions were validated with gel electrophoresis. All proposed reactions exhibit a hybridization complex with a molecular mass >1.5k base pairs, which is clear evidence of chain reaction. The hybridization efficiency trend revealed by gel electrophoresis corresponds nicely to the simulated data from the algorithm. The HCR reactions and the corresponding algorithm serve as a basis to further SARS-CoV-2 sensing applications and facilitate better screening strategies for the prevention of on-going pandemics.


Internal dynamics in bound states of unequal solitons.
The bound states (BSs) of solitons are found to have intriguing internal dynamics in ultrafast lasers. Here, we explore the binding mechanism and internal motions of asymmetric bound state (ABS) solitons constituted by unequal solitons at short-range with their tails directly overlapped. Experiments and simulations show that the periodic energy flux between two solitons, mediated by their overlapped tails, gives rise to a balanced separation and energy distribution across the ABS. The motion mechanisms of strong and weak solitons are discussed in detail. This work provides insights into the binding mechanism and internal dynamics of BSs.


Evaluation of the Toxicity and Toxicokinetics of Cereulide from an Emetic Bacillus cereus Strain of Milk Origin.
Bacillus cereus is an opportunistic foodborne agent causing food poisoning and many infectious diseases. The heat-stable emetic toxin cereulide is one of the most prevalent toxins produced by pathogenic B. cereus, resulting in symptoms such as emesis and liver failure. In the present work, the toxicity and toxicokinetics of cereulide from an emetic B. cereus isolate (CAU45) of raw milk were evaluated. The production of cereulide was tested by a cytotoxicity test and enzyme immunoassay, and confirmed by the presence of the ces (cereulide synthetase) gene and the ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method. All results showed that the amount and toxicity of cereulide produced by CAU45 was 7 to 15.3 folds higher than the reference emetic B. cereus DSMZ 4312. Cereulide in plasma was collected at different time points after a single intravenous injection to evaluate its toxicokinetics in rabbits. The maximum concentration of cereulide was achieved in 2.6 ± 3.4 h after administration, with the elimination half-life of 10.8 ± 9.1 h, which expands our understanding of the toxic effects of cereulide. Together, it suggests that urgent sanitary practices are needed to eliminate emetic toxins and emetic B. cereus in raw milk.


Goal-setting protocol in adherence to exercise by Italian adults.
A goal-setting protocol, based on research in goal setting and performance and personal construct theory, was tested for its effect on adherence to a new exercise program. The Goal-setting group (n = 50) had significantly less dropout (30%) than the control group (n = 50) (74%). The Goal-setting group also had significantly better attendance (p<.0001). Suggestions for increasing confidence in findings through further research and practical implications of using the protocol to improve exercise maintenance across settings were discussed.


Potential Role of Ginger (Zingiber officinale Roscoe) in the Prevention of Neurodegenerative Diseases.
Ginger is composed of multiple bioactive compounds, including 6-gingerol, 6-shogaol, 10-gingerol, gingerdiones, gingerdiols, paradols, 6-dehydrogingerols, 5-acetoxy-6-gingerol, 3,5-diacetoxy-6-gingerdiol, and 12-gingerol, that contribute to its recognized biological activities. Among them, the major active compounds are 6-shogaol and 6-gingerol. Scientific evidence supports the beneficial properties of ginger, including antioxidant and anti-inflammatory capacities and in contrast, a specific and less studied bioactivity is the possible neuroprotective effect. The increase in life expectancy has raised the incidence of neurodegenerative diseases (NDs), which present common neuropathological features as increased oxidative stress, neuroinflammation and protein misfolding. The structure-activity relationships of ginger phytochemicals show that ginger can be a candidate to treat NDs by targeting different ligand sites. Its bioactive compounds may improve neurological symptoms and pathological conditions by modulating cell death or cell survival signaling molecules. The cognitive enhancing effects of ginger might be partly explained via alteration of both the monoamine and the cholinergic systems in various brain areas. Moreover, ginger decreases the production of inflammatory related factors. The aim of the present review is to summarize the effects of ginger in the prevention of major neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and multiple sclerosis.


The frequency of oligopurine.oligopyrimidine and other two-base tracts in yeast chromosome III.
The TRACTS program was employed to map the occurrence of base tracts composed of only two bases in Saccharomyces cerevisiae chromosome III. The observed frequencies were compared with those expected in random DNA. A vast excess of long base tracts of the three possible two-base combinations, namely, purine.pyrimidine (R.Y), keto.imino (K.M) and weak;strong (W;S, mainly A,T rich), was documented. The observed excess places yeast in the same category as other eukaryote and organelle genomes analysed. The excess of the two-base tracts was considerably larger in the 1/3 of the chromosome not coding for a protein, in particular proximal to coding initiation and termination sites, but was observed for coding regions as well. A functional role for the excessive tracts, possibly as unwinding centers of particular genes, is proposed. Multiple occurrence of long two-base tracts is offered as another diagnostic to determine whether an open reading frame (ORF), or an ORF subregion, is an actually translated gene region.


3-D phantom and in vivo cardiac speckle tracking using a matrix array and raw echo data.
Cardiac motion has been tracked using various methods, which vary in their invasiveness and dimensionality. One such noninvasive modality for cardiac motion tracking is ultrasound. Three-dimensional ultrasound motion tracking has been demonstrated using detected data at low volume rates. However, the effects of volume rate, kernel size, and data type (raw and detected) have not been sufficiently explored. First comparisons are made within the stated variables for 3-D speckle tracking. Volumetric data were obtained in a raw, baseband format using a matrix array attached to a high parallel receive beam count scanner. The scanner was used to acquire phantom and human in vivo cardiac volumetric data at 1000-Hz volume rates. Motion was tracked using phase-sensitive normalized cross-correlation. Subsample estimation in the lateral and elevational dimensions used the grid-slopes algorithm. The effects of frame rate, kernel size, and data type on 3-D tracking are shown. In general, the results show improvement of motion estimates at volume rates up to 200 Hz, above which they become stable. However, peak and pixel hopping continue to decrease at volume rates higher than 200 Hz. The tracking method and data show, qualitatively, good temporal and spatial stability (for independent kernels) at high volume rates.


Dissemination of linezolid-dependent, linezolid-resistant Staphylococcus epidermidis clinical isolates belonging to CC5 in German hospitals.
Linezolid-resistant Staphylococcus epidermidis (LRSE) and linezolid-dependent ST22 strains have been shown to predominate in tertiary care facilities all over Greece. We report herein the dissemination of ST22 but also ST2, ST5 and ST168 linezolid-dependent LRSE clones in four unrelated German hospitals. Fourteen LRSE clinical isolates recovered during 2012-14 from five distantly located German hospitals were tested by for MIC determination broth microdilution and Etest, PCR/sequencing for cfr and for mutations in 23S rRNA, rplC, rplD and rplV genes, MLST, PFGE and growth curves without and with linezolid at 16 and 32 mg/L. Most (11, 78.6%) isolates had linezolid MICs >256 mg/L. Five isolates carried the cfr gene. Eight isolates belonged to ST22, two isolates each to ST168 and ST2 and one isolate each to ST5 and ST23. Ten isolates [seven belonging to ST22 and one to each of ST2, ST5 and ST168; all these STs belong to clonal complex (CC) 5] exhibited linezolid-dependent growth, growing significantly faster in linezolid-containing broth. Four isolates were non-dependent (one belonging to each of ST22, ST2, ST23 and ST168). Four isolates came from three different hospitals, whereas four and six isolates were recovered during outbreaks of LRSE in two distinct hospitals. The multi-clonal dissemination of CC5 linezolid-dependent LRSE throughout German hospitals along with the clonal expansion of ST22 linezolid-dependent LRSE in Greek hospitals is of particular concern. It is plausible that this characteristic is inherent and provides a selective advantage to CC5 LRSE under linezolid pressure, contributing to their dissemination throughout hospitals in these countries.


Nuclear translocation of beta-catenin protein but absence of beta-catenin and APC mutation in gastrointestinal carcinoid tumor.
Carcinoid tumors are a group of heterogeneous tumors with neuroendocrine differentiation and are mainly located in the gastrointestinal tract. A high frequency of cytoplasmic accumulation and/or nuclear translocation of beta-catenin with frequent mutations of exon 3 of beta-catenin gene in gastrointestinal carcinoid tumor has been previously described, but the role of Wnt/beta-catenin/APC pathway in the genesis of carcinoid tumor remains largely unknown. To further characterize the role of Wnt/beta-catenin/APC pathway, we investigated 91 gastrointestinal carcinoid tumors and, for comparison, 26 extragastrointestinal carcinoid tumors by immunohistochemical detection of beta-catenin protein and direct sequencing of exon 3 of the beta-catenin gene and exon 15 of the APC gene. Cytoplasmic accumulation and/or nuclear translocation of beta-catenin were found in 27 gastrointestinal carcinoid tumors (29.7%) but not in any extragastrointestinal carcinoid tumors. Interestingly, neither beta-catenin nor APC gene mutation was detected in all of the cases with nuclear expression of beta-catenin. Our results indicate that the role beta-catenin plays in the genesis of gastrointestinal and extragastrointestinal carcinoid tumors is different. Nuclear expression of beta-catenin does not occur in extragastrointestinal carcinoid tumors, and mutation of exon 3 of beta-catenin gene and exon 15 of APC gene does not contribute to the activation of Wnt/beta-catenin/APC pathway in gastrointestinal carcinoid tumors.


Value of syndromic surveillance within the Armed Forces for early warning during a dengue fever outbreak in French Guiana in 2006.
A dengue fever outbreak occured in French Guiana in 2006. The objectives were to study the value of a syndromic surveillance system set up within the armed forces, compared to the traditional clinical surveillance system during this outbreak, to highlight issues involved in comparing military and civilian surveillance systems and to discuss the interest of syndromic surveillance for public health response. Military syndromic surveillance allows the surveillance of suspected dengue fever cases among the 3,000 armed forces personnel. Within the same population, clinical surveillance uses several definition criteria for dengue fever cases, depending on the epidemiological situation. Civilian laboratory surveillance allows the surveillance of biologically confirmed cases, within the 200,000 inhabitants. It was shown that syndromic surveillance detected the dengue fever outbreak several weeks before clinical surveillance, allowing quick and effective enhancement of vector control within the armed forces. Syndromic surveillance was also found to have detected the outbreak before civilian laboratory surveillance. Military syndromic surveillance allowed an early warning for this outbreak to be issued, enabling a quicker public health response by the armed forces. Civilian surveillance system has since introduced syndromic surveillance as part of its surveillance strategy. This should enable quicker public health responses in the future.


Discovering anomalies in big data: a review focused on the application of metaheuristics and machine learning techniques.
With the increase in available data from computer systems and their security threats, interest in anomaly detection has increased as well in recent years. The need to diagnose faults and cyberattacks has also focused scientific research on the automated classification of outliers in big data, as manual labeling is difficult in practice due to their huge volumes. The results obtained from data analysis can be used to generate alarms that anticipate anomalies and thus prevent system failures and attacks. Therefore, anomaly detection has the purpose of reducing maintenance costs as well as making decisions based on reports. During the last decade, the approaches proposed in the literature to classify unknown anomalies in log analysis, process analysis, and time series have been mainly based on machine learning and deep learning techniques. In this study, we provide an overview of current state-of-the-art methodologies, highlighting their advantages and disadvantages and the new challenges. In particular, we will see that there is no absolute best method, i.e., for any given dataset a different method may achieve the best result. Finally, we describe how the use of metaheuristics within machine learning algorithms makes it possible to have more robust and efficient tools.


Could Salivary Cyclosporine Dosage Replace the Whole Blood Cyclosporine Measurements in Renal Transplant Patients?
Cyclosporin (CsA) has been extensively used as the immunosuppressant of choice in renal transplantation. Currently available approaches to assess CsA levels, both in serum and blood, fail to accurately reflect the concentration of the pharmacologically active drug fraction. Free CsA levels in biological fluids (blood or saliva) have been advocated to play an important role. Traditional salivary CsA monitoring tests are based on available archaic salivary techniques that are nonspecific and require large amounts of saliva. The aim of this study was to assess salivary CsA correlation using a novel and more accurate technique and to correlate with CsA levels in blood. Patients provided blood samples of 2 ml and 2 ml of unstimulated saliva on the same day 2 h after the morning CsA dose (C2). Whole blood levels of CsA were determined using the monoclonal fluorescent polarization immunoassay (FPIA) kit. The FPIA kit was adapted to salivary testing by using a novel extraction method developed and patented under the name of Middle East Research Institute (MERI). Wilcoxon signed rank test compared the differences in blood and salivary CsA. Pearson's correlation coefficient assessed the linear association between blood and salivary CsA concentrations. All analyses were performed using IBM-SPSS version 23 (IBM Corp, Armonk, NY, USA). No significant correlation was observed between blood and salivary CsA levels. Salivary CsA concentrations at C2 cannot adequately replace C2 blood levels as an indicator of CsA bioavailability despite improved performance of monoclonal FPIA and application of the MERI technique. More studies may be warranted to design more reliable and less invasive procedures for therapeutic drug monitoring.


GCN2 regulates pancreatic β cell mass by sensing intracellular amino acid levels.
EIF2AK4, which encodes the amino acid deficiency-sensing protein GCN2, has been implicated as a susceptibility gene for type 2 diabetes in the Japanese population. However, the mechanism by which GCN2 affects glucose homeostasis is unclear. Here, we show that insulin secretion is reduced in individuals harboring the risk allele of EIF2AK4 and that maintenance of GCN2-deficient mice on a high-fat diet results in a loss of pancreatic β cell mass. Our data suggest that GCN2 senses amino acid deficiency in β cells and limits signaling by mechanistic target of rapamycin complex 1 to prevent β cell failure during the consumption of a high-fat diet.


Diagnosis and surgical treatment of intrabiliary ruptured hydatid disease of the liver.
The major complication of hydatid disease of the liver is intrabiliary rupture of the cyst. The purpose of this study was to evaluate the outcome of patients with intrabiliary ruptured hydatid disease of the liver. Using a standardised data collection instrument, case records of patients who were operated on for hydatid disease of the liver diagnosed between January 1990 and December 2001 at Dicle University Hospital (DUH) were searched and 192 patients who had been operated for hydatid disease of the liver were detected. Of these, 20 patients (16 females, 4 males) were retrospectively reviewed for intrabiliary ruptured hydatid disease of the liver. Intrabiliary ruptured hydatid disease of the liver was determined in 10.4% (N = 20) of the patients (N = 192) operated for hydatid disease of the liver. The average age of patients was 38.9 +/- 14.05 years (range 20 - 72 years). The duration of the symptoms was 3.4 +/- 2.13 years (range 1 - 8 years). The most frequent symptoms were right upper quadrant/epigastric pain, dyspepsia, jaundice and pruritus. Diagnosis of hydatid cyst was principally made using ultrasonography. Twelve cysts (60%) were located in the right lobe, 5 (25%) in the left lobe, and 3 (15%) in the right and left lobes. The size of the cysts was 12.6 +/- 5.79 cm (range 6 - 20 cm). The average diameter of the common bile duct (CBD) was 20.45 +/- 8.54 mm (range 10 - 40 mm). Dilated CBD in 16 patients (80%) and daughter cysts and debris in the CBD in 10 patients (50%) were found during operation. Partial cystectomy and capitonnage were performed in all patients. In addition, T-tube drainage in 17 patients, omentoplasty plus T-tube drainage in 2 patients and choledochoduodenostomy in 1 patient were carried out during operation. An internal opening of the biliary fistula was found and sutured in 12 patients (60%). Wound infections developed in 6 patients (30%), suppuration of the residual cavity in 4 patients, and wound dehiscence in 2 patients. Two patients (10%) died from sepsis-multiple organ failure and hepatic failure. The average period of hospitalisation was 28.75 +/- 19.1 days (range 10 - 103 days). If bile-stained cystic fluid and a dilated CBD is found in patients with hydatid disease of the liver, choledochal exploration should be performed during operation. T-tube drainage may be preferred in the management of intrabiliary ruptured hydatid disease because of low morbidity, the ability to decompress intrabiliary pressure, easier monitoring of the biliary drainage and smaller alteration of the anatomy.


[Medico-psychology in Huang di nei jing (Yellow Emperor's Inner Canon)].
Huang di nei jing (Yellow Emperor's Inner Canon) discusses spirit, mood, soul, idea, will, anxiety, worry, wisdom, morale and their relations with human life, physiology, and body-mind health. It also expounds the developmental rule of human body and mind, methods for keeping fit. These simple thinking of medico-psychology reflects that Chinese doctors had advocated science since ancient times. The methodology of systematically and comprehensively discussing the relationship among nature, human body, visceral functions, and emotional activities reflects, again, the rather strong physiological dialectical thinking of ancient people.


Studies on sulfite reduction by Desulfovibrio vulgaris.
Dissimilatory reduction of sulfites by Desulfovibrio vulgaris was investigated. Medium with alpha-glycerophosphate as a source of organic carbon and phosphorus was applied. It was found that sulfite at the concentration up to 1M Na2SO3 is not toxic for D. vulgaris and acts efficiently as an electron acceptor. Basing on the presented results, a general mechanism of microbiological transformation of sulfites is proposed.


Present Status of Microsurgical Replantation.
The replantation of amputated parts has stimulated the imagination of writers since antiquity. It was not until the successful replantation of an arm by Malt and a hand by Chen Chung Wei in 1953 that these fables became reality. The simultaneous development of the field of microsurgery permitting the repair of one millimetre vessels made possible the replantation of structures fed by these small vessels such as fingers, ears, noses, lips, scalps and penises.


Preoperative Prognostic Nutrition Index as a Prognostic Indicator of Survival in Elderly Patients Undergoing Gastric Cancer Surgery.
Gastric cancer is a common tumor type associated with nutritional and immune status. The aim of the current study was to investigate the prognostic value of a preoperative prognostic nutritional index (PNI), composed of nutritional factors and immune factors in elderly patients undergoing gastric cancer surgery. A total of 454 patients undergoing gastric cancer surgery were divided into two groups based on preoperative PNI scores: ≤45.1 (n = 307) and >45.1 (n = 147). Survival analysis was performed using the Kaplan-Meier method and Log rank tests. Univariate and multivariate analyses were conducted to identify independent prognostic factors using a Cox proportional hazards model. According to the X-tile program, the optimal cutoff value for predicting overall survival (OS) with the PNI was 45.1. The receiver operating characteristic analysis revealed that PNI exhibited 70.6% sensitivity and 56.5% specificity for predicting death during long-term follow-up. The cumulative incidence of postoperative 4-year mortality indicated that the risk of death increased significantly for PNI ≤45.1. In multivariate analysis, preoperative PNI was a significant independent predictor of mortality. In the age-stratified subgroup analysis, preoperative PNI was more sensitive for the old elderly subgroup than for the young elderly subgroup. Preoperative PNI is a sensitive and specific prognostic predictor among elderly patients undergoing gastric cancer surgery.


Computed tomography-guided implantation of 125I seeds brachytherapy for recurrent multiple pulmonary oligometastases: initial experience and results.
To retrospectively evaluate the efficacy and safety of computed tomography (CT)-guided percutaneous interstitial brachytherapy using 125I radioactive seeds for multiple pulmonary metastatic tumors. Between September 2013 and December 2015, 22 patients with multiple pulmonary metastases, who after conventional chemotherapy and trans-arterial chemoembolization (TACE) therapy were considered unable to withstand stereotactic body radiation therapy (SBRT), received CT-guided 125I brachytherapy. Clinical data were studied retrospectively. A planning target volume of 90% (D90) was 120-160 Gy for 125I seeds with an activity of 25.9 MBq. A CT-based evaluation performed 1, 2, and 6 months' post-implantation enabled review of local control of tumors. Twenty-two patients with 65 pulmonary metastases successfully completed treatment. The mean value for D90 for implantation for 125I seeds was 132 Gy. Complete response (CR) + partial response (PR) was documented in 81.54%, 78.46%, and 78.46% of patients at 1, 2, and 6 months after implantation, respectively. Fourteen out of 22 patients had CR, 3 had PR, 2 had stable disease (SD), and 3 had progressive disease (PD). Most of the metastases (CR + PR + SD; 87.69% after 6 months) were controlled by implantation. CT-guided 125I brachytherapy is a safe and effective treatment for multiple pulmonary metastatic tumors, and can achieve good short-term local control, so long as the radiation dose is sufficient.


Asymmetry of mandibular dentition is associated with dietary specialization in snail-eating snakes.
In vertebrates, the left-and-right pairs of homologous organs are generally present in equal numbers. A remarkable exception is snail-eating snakes in the family Pareidae: almost all the pareid snakes have much more teeth on the right mandible than on the left for functional specialization in feeding on the dextral majority of land snails. Because the only exceptional species with symmetric dentition has been regarded as a slug-eater, the extent of dietary specialization on slugs could shape the degree of the lateral asymmetry of mandibular dentition (dentition asymmetry) even among snail eaters. To test this, I compared the morphology and behavior of two sympatric species of Taiwanese snail-eating snakes, Pareas atayal and P. formosensis. Specimens collected in the same locality showed that the dentition asymmetry of P. formosensis was significantly smaller than that of P. atayal. Congruent to its weak asymmetry, P. formosensis showed a strong preference of slugs to snails in the feeding experiment. The dietary specialization of P. formosensis on slugs would contribute to niche partitioning from the sympatric congener P. atayal. This study suggests that the diverse variation in the dentition asymmetry of pareid snakes is the result of their dietary specialization and divergence.


The effect of increasing dairy calcium intake of adolescent girls on changes in body fat and weight.
Background: Overweight is epidemic in adolescents and is a major concern because it tracks into adulthood. Evidence supports the efficacy of high-calcium, high-dairy diets in achieving healthy weight in adults. However, no randomized controlled trials of the effect of dairy food on weight and body fat in adolescents have been reported to our knowledge.Objective: The aim was to determine whether increasing calcium intake to recommended amounts with dairy foods in adolescent girls with habitually low calcium intakes would decrease body fat gain compared with girls who continued their low calcium intake. Participants had above-the-median body mass index (BMI; in kg/m2).Design: We enrolled 274 healthy postmenarcheal 13- to 14-y-old overweight girls who had calcium intakes of ≤600 mg/d in a 12-mo randomized controlled trial. Girls were randomly assigned in a 1:1 ratio to 1 of 2 groups within each of 3 BMI percentiles: 50th to <70th, 70th to <85th, and 85th to <98th. The assignments were 1) dairy, which included low-fat milk or yogurt servings providing ≥1200 mg Ca/d or 2) control, which included the usual diet of ≤600 mg Ca/d.Results: We failed to detect a statistically significant difference between groups in percentage of body fat gain over 12 mo (mean ± SEM: dairy 0.40% ± 0.53% > control; P < 0.45). The effect of the intervention did not differ by BMI percentile stratum. There was no difference in weight change between the 2 groups.Conclusion: Our findings that the dairy group gained body fat similar to the control group provide no support for dairy food as a stratagem to decrease body fat or weight gain in overweight adolescent girls. This trial was registered at clinicaltrials.gov as NCT01066806.


Adhesive Leaf Created by a Corona Discharge.
Here, we report a new concept of both the adhesive manner and material, named "adhesive leaf (AL)," based on the leaf of the plant Heteropanax fragrans. The treatment of the corona discharge on the leaf surface can cause the nano-/microdestruction of the leaf epidermis, resulting in an outward release of sap. The glucose-containing sap provided the AL with a unique ability to stick to various substrates such as steel, polypropylene, and glass. Moreover, we reveal that the AL adhesion strength depends on the AL size, as well as the corona-discharge intensity. Conventional adhesives, such as glue and bond, lose their adhesive property and leave dirty residues upon the removal of the attached material. Unlike the conventional methods, the AL is advantageous as it can be repeatedly attached and detached thoroughly until the sap liquid is exhausted; its adhesive ability is maintained for at least three weeks at room temperature. Our findings shed light on a new concept of a biodegradable adhesive material that is created by a simple surface treatment.


Marked effects of alloying on the thermal conductivity of nanoporous materials.
We show that porous alloys can display thermal conductivity reductions at considerably larger pore sizes than nonalloyed porous materials of the same nominal porosity. The thermal conductivity of Si0.5Ge0.5 alloy with 0.1 porosity becomes half the nonporous value at 1000 nm pore sizes, whereas pores smaller than 100 nm are required to achieve the same relative reduction in pure Si or Ge. Using Monte Carlo simulations, we also show that previous models had overestimated the thermal conductivity in the small pore limit. Our results imply that nanoporous alloys should be advantageous with respect to nanoporous nonalloys, for applications requiring a low thermal conductivity, such as novel thermoelectrics.