Variation in initial and continued use of primary, mental health, and specialty video care among Veterans.
To identify which Veteran populations are routinely accessing video-based care. National, secondary administrative data from electronic health records at the Veterans Health Administration (VHA), 2019-2021. This retrospective cohort analysis identified patient characteristics associated with the odds of using any video care; and then, among those with a previous video visit, the annual rate of video care utilization. Video care use was reported overall and stratified into care type (e.g., primary, mental health, and specialty video care) between March 10, 2020 and February 28, 2021. Veterans active in VA health care (>1 outpatient visit between March 11, 2019 and March 10, 2020) were included in this study. Among 5,389,129 Veterans in this evaluation, approximately 27.4% of Veterans had at least one video visit. We found differences in video care utilization by type of video care: 14.7% of Veterans had at least one primary care video visit, 10.6% a mental health video visit, and 5.9% a specialty care video visit. Veterans with a history of housing instability had a higher overall rate of video care driven by their higher usage of video for mental health care compared with Veterans in stable housing. American Indian/Alaska Native Veterans had reduced odds of video visits, yet similar rates of video care when compared to White Veterans. Low-income Veterans had lower odds of using primary video care yet slightly elevated rates of primary video care among those with at least one video visit when compared to Veterans enrolled at VA without special considerations. Variation in video care utilization patterns by type of care identified Veteran populations that might require greater resources and support to initiate and sustain video care use. Our data support service specific outreach to homeless and American Indian/Alaska Native Veterans.


A novel multi-detection technique for three-dimensional reciprocal-space mapping in grazing-incidence X-ray diffraction.
A new scattering technique in grazing-incidence X-ray diffraction geometry is described which enables three-dimensional mapping of reciprocal space by a single rocking scan of the sample. This is achieved by using a two-dimensional detector. The new set-up is discussed in terms of angular resolution and dynamic range of scattered intensity. As an example the diffuse scattering from a strained multilayer of self-assembled (In,Ga)As quantum dots grown on GaAs substrate is presented.


Ability of preoperative serum prostate-specific antigen value to predict pathologic stage and DNA ploidy. Influence of clinical stage and tumor grade.
Although the preoperative serum prostate-specific antigen (PSA) concentration has been demonstrated to be directly proportional to pathologic stage, it has been found to be unreliable for predicting final pathologic stage on an individual basis. Statistical analysis was thus performed to determine whether combining various preoperative parameters could enhance the predictive power of PSA. Multivariate logistic regression analysis revealed that, indeed, local clinical stage (determined by digital rectal examination) and tumor grade (determined from the biopsy specimen) significantly enhanced the predictive power of PSA (P < 0.0001 and < 0.0001, respectively). These preoperative parameters were thus all combined into a model from which probability plots were generated. These probability plots allow the practicing urologist to estimate preoperatively for an individual patient the probability of a given pathologic stage and DNA ploidy status. For example, the predicted probability of organ-confined disease for a patient with a PSA value of 10 ng/mL, when used alone, is 53 percent. However, the predicted probability of organ-confined disease for a patient with a PSA value of 10 ng/mL, clinical Stage B2, and high-tumor grade is only 30 percent. Thus, the findings of this investigation allow the physician maximal use of the preoperative variables to discuss more accurately with the patient what might be expected at the time of operation and to plan more precisely the surgical procedure that will possibly ensure complete removal of the prostate cancer with the least compromise to normal physiologic function (continence and potency).


Surgical results in women with detrusor underactivity and stress urinary incontinence undergoing suburethral sling procedure-Predictive factors for successful outcome.
To elucidate the treatment results and predictors for successful outcome in women with detrusor underactivity (DU) and stress urinary incontinence (SUI) undergoing suburethral sling procedure. Medical records of women with coexistent SUI and DU treated with a suburethral sling were retrospectively reviewed and we analyzed the association between treatment outcome and baseline demographics including etiology of DU and urodynamic variables. Patients who were dry and could urinate spontaneously were considered successful. Treatment failure was considered in those who were dry but needing clean intermittent catheterization (CIC) and patients who were still wet. Urogenital Distress Inventory (UDI-6) and Incontinence Impact Questionnaire (IIQ-7) scores were used to assess the impact of surgery on the quality of life. Among 71 patients, a successful outcome was noted in 39 (55%), failed outcome with CIC in 15 (21%), and totally treatment failure in 17 (24%). Treatment outcome did not differ among the etiology subgroups. Overall, UDI-6 and IIQ-7 scores significantly improved after surgery. Multivariable logistic regression analysis revealed that the IIQ-7 and maximum flow rate (Qmax) were two independent predictors for improvement after surgery. An IIQ-7 score ≤6, and Qmax ≥6 mL/s can predict improvement by receiver operating characteristic analysis. Qmax ≤6 mL/s can predict needing CIC after surgery. For women with SUI and coexistent DU who underwent suburethral sling procedure, low IIQ-7 (≤6) scores and higher Qmax (≥6 mL/s) are predictors for improvement of surgical outcome. A Qmax of <6 mL/s was the only predictor for CIC after surgery.


Math1 expression redefines the rhombic lip derivatives and reveals novel lineages within the brainstem and cerebellum.
The rhombic lip (RL) is an embryonic proliferative neuroepithelium that generates several groups of hindbrain neurons. However, the precise boundaries and derivatives of the RL have never been genetically identified. We use beta-galactosidase expressed from the Math1 locus in Math1-heterozygous and Math1-null mice to track RL-derived cells and to evaluate their developmental requirements for Math1. We uncover a Math1-dependent rostral rhombic-lip migratory stream (RLS) that generates some neurons of the parabrachial, lateral lemniscal, and deep cerebellar nuclei, in addition to cerebellar granule neurons. A more caudal Math1-dependent cochlear extramural stream (CES) generates the ventral cochlear nucleus and cochlear granule neurons. Similarly, mossy-fiber precerebellar nuclei require Math1, whereas the inferior olive and locus coeruleus do not. We propose that Math1 expression delimits the extent of the rhombic lip and is required for the generation of the hindbrain superficial migratory streams, all of which contribute neurons to the proprioceptive/vestibular/auditory sensory network.


Application of passive sampling on assessment of concentration distribution and health risk of volatile organic compounds at a high-tech science park.
The objectives of this study are to investigate the volatile organic compound (VOC) distribution using passive samplers and to assess the resulting health risks in a high-tech science industrial park. With the advantages of passive sampling techniques, long-term and wide-area samples are collected. The results show TVOC concentrations in summer, fall, winter, and spring are 7.14 ± 5.66 ppb, 18.17 ± 5.81 ppb, 10.30 ± 3.54 ppb, and 14.56 ± 4.53 ppb, respectively; those on weekdays and weekends are 14.36 ± 6.80 ppb and 9.87 ± 4.86 ppb, respectively; and those in industrial and residential zones are 12.97 ± 0.39 ppb and 11.13 ± 0.68 ppb, respectively. Based on concentration variations, and benzene, toluene, ethylbenzene, and xylene ratios, we can resolve the source origins. Health risks are assessed based on the resulting concentrations. In the case of non-cancer chronic effects, long-term exposure to these concentrations does not support there is a risk of adverse health effects. However, potential cancer risks of exposure to these concentrations may occur, especially to carbon tetrachloride and benzene. By applying this study's procedures, information on VOC concentration distribution, source identification, and health assessment can be obtained and they are applicable to similar studies.


Clinical characteristics of human immunodeficiency virus patients being referred for liver transplant evaluation: a descriptive cohort study.
Liver transplantation (LT) is a treatment option for select human immunodeficiency virus (HIV)-infected patients with advanced liver disease. The aim of this study was to describe LT evaluation outcomes in HIV-infected patients. All HIV-infected patients referred for their first LT evaluation at the Mount Sinai Medical Center were included in this retrospective, descriptive cohort study. Multivariable logistic regression was used to identify factors independently associated with listing. Between February 2000 and April 2012, 366 patients were evaluated for LT, with 66 (18.0%) listed for LT and 300 (82.0%) not listed. Fifty-one patients (13.9%) died before completing evaluation and 85 (23.2%) were too early for listing. Reasons patients were declined for listing were psychosocial (15.8%), HIV-related (10.4%), loss to follow-up (9.6%), surgical/medical (6.0%), liver-related (4.4%), patient choice (3.4%), and financial (1.6%). Listed patients were more likely to have hepatocellular carcinoma (HCC) (43.1% vs. 17.1%; P < 0.0001) and less likely to have hepatitis B (6.2% vs. 15.7%; P = 0.04) or a psychiatric history (19.7% vs. 35.2%; P = 0.02) than those not listed. In multivariable analysis, HCC (odds ratio [OR] 5.79; 95% confidence interval [95% CI]: 2.97-11.28), model for end-stage liver disease (MELD) score at referral (OR 1.06; 95% CI 1.01-1.11), and hepatitis B (OR 0.26; 95% CI 0.08-0.79) were associated with listing. MELD score and HCC were positive predictors of listing in HIV-infected patients referred for LT evaluation and, therefore, timely referrals are vital in these patients. As MELD is a predictor for death while undergoing evaluation, rapid evaluation should be performed in HIV-infected patients with a higher MELD score.


Reactions of glutathione with the catechol, the ortho-quinone and the semi-quinone free radical of etoposide. Consequences for DNA inactivation.
Etoposide [4'-demethylepipodophyllotoxin-9-(4,6-O-ethylidene-beta- D-glucopyranoside)] can be metabolized to DNA-inactivating catechol, ortho-quinone and semi-quinone free radical derivatives which may contribute to its cytotoxicity. In this paper, we examined in vitro whether glutathione (GSH), which is known to react easily with quinoid compounds, could interact with the active etoposide intermediates and in this way influence the cytotoxicity of the parent compound. To this end, reactions of GSH with the etoposide intermediates were studied, using HPLC and ESR measurements, together with the effects of GSH on the biological inactivation of single-stranded (ss) and double-stranded (RF) phi X174 DNA by these compounds. From the results it could be determined that: (a) GSH does not react with the catechol and, as a consequence, has no effect on the reaction of this intermediate of etoposide with ss and RF phi X174 DNA; (b) GSH reacts with the ortho-quinone most likely by formation of a conjugate and by two-electron reduction to the catechol, resulting in a partial protection of ss and RF phi X174 DNA against inactivation by this species; and (c) GSH protects ss phi X174 DNA against inactivation by the semi-quinone free radical of etoposide probably by conjugation with this species.


A new psoralen-containing gel for topical PUVA therapy: development, and treatment results in patients with palmoplantar and plaque-type psoriasis, and hyperkeratotic eczema.
Topical photochemotherapy with psoralen and its derivatives 4,5',8-trimethylpsoralen (TMP) and 8-methoxypsoralen (8-MOP), with UVA irradiation, was evaluated with regard to minimum phototoxic dose, concentration, timing of UVA irradiation and systemic and local side-effects, in healthy volunteers. Psoralen (0.005%) in aqueous gel was found to be superior to TMP and 8-MOP in aqueous gel. No hyperpigmentation was seen after topical PUVA treatment with psoralen in aqueous gel. Patients with plaque-type psoriasis (n = 7), palmoplantar psoriasis (n = 7) and hyperkeratotic eczema (n = 2) were treated. Topical PUVA therapy was effective in most psoriasis patients, without the occurrence of local or systemic side-effects. Moreover, hyperkeratotic eczema patients who did not respond to conventional therapy showed partial remission. These results indicate that topical PUVA therapy with psoralen in aqueous gel is a useful therapeutic modality for treatment of psoriasis patients, and patients with recalcitrant dermatoses such as palmoplantar psoriasis and hyperkeratotic eczema.


Isolation and structural elucidation of unique γ-oryzanol species in rice bran oil.
Even though γ-oryzanol (OZ) such as 24-methylenecycloartanyl ferulate (24MCAFA) is abundant in purified rice bran oil, we realized that the oil contained the prospect of two additional novels of OZ species. To identify this, we isolated and analyzed their chemical structures by using HPLC-UV-MS, NMR, and IR. We revealed for the first time that the oil had also contained cyclobranyl ferulate (CBFA) and cyclosadyl ferulate (CSFA) which are likely to be exist due to the isomerism of 24MCAFA under acid condition. OZ profile including CBFA and CSFA was roughly similar between commercial rice bran oils and processed foods containing the oils, suggesting that people might have often consumed CBFA and CSFA from rice bran oils and/or processed foods. Since different OZ species are known to have different functionality, this study opens the chance to explore more the contribution of CBFA and CSFA for human health and wellness.


Direct tumor recognition by a human CD4(+) T-cell subset potently mediates tumor growth inhibition and orchestrates anti-tumor immune responses.
Tumor antigen-specific CD4(+) T cells generally orchestrate and regulate immune cells to provide immune surveillance against malignancy. However, activation of antigen-specific CD4(+) T cells is restricted at local tumor sites where antigen-presenting cells (APCs) are frequently dysfunctional, which can cause rapid exhaustion of anti-tumor immune responses. Herein, we characterize anti-tumor effects of a unique human CD4(+) helper T-cell subset that directly recognizes the cytoplasmic tumor antigen, NY-ESO-1, presented by MHC class II on cancer cells. Upon direct recognition of cancer cells, tumor-recognizing CD4(+) T cells (TR-CD4) potently induced IFN-γ-dependent growth arrest in cancer cells. In addition, direct recognition of cancer cells triggers TR-CD4 to provide help to NY-ESO-1-specific CD8(+) T cells by enhancing cytotoxic activity, and improving viability and proliferation in the absence of APCs. Notably, the TR-CD4 either alone or in collaboration with CD8(+) T cells significantly inhibited tumor growth in vivo in a xenograft model. Finally, retroviral gene-engineering with T cell receptor (TCR) derived from TR-CD4 produced large numbers of functional TR-CD4. These observations provide mechanistic insights into the role of TR-CD4 in tumor immunity, and suggest that approaches to utilize TR-CD4 will augment anti-tumor immune responses for durable therapeutic efficacy in cancer patients.


Phylogenetic analysis and molecular characterization of the co-infection of the new variant of the porcine epidemic diarrhea virus and the novel porcine kobuvirus isolated from piglets with diarrhea.
Porcine epidemic diarrhea virus (PEDV) is a virus that can cause diarrhea in pigs, resulting in significant economic losses to the pig industry. The mutation of the virus and its co-infection with other enteroviruses leads to poor control of PEDV infection. In this study, we found that the diarrhea outbreak in a pig farm in Shandong Province was mainly caused by PEDV infection. Through high-throughput sequencing, we also detected one other diarrhea-related virus (porcine kobuvirus). In the phylogenetic analysis and molecular characterization of the detected PEDV S gene and PKV, it was found that the S gene of the PEDV strain detected in this study (named SD22-2) had more mutations than the CV777 strain. The highest homology between PKV (named SD/2022/China) detected in this study and other strains was only 89.66%. Based on polyprotein, we divided SD/2022/China strains into a new grouping (designated group 4) and detected recombination signals. In summary, SD22-2 detected in this study is a new PEDV variant strain, and SD/2022/China strain might be a novel PKV strain. We also found the co-infection of the new PEDV variant and the novel PKV isolated from piglets with diarrhea. Our data suggested the importance of continuous surveillance of PEDV and PKV.


Improvement in mismatch negativity generation during d-serine treatment in schizophrenia: Correlation with symptoms.
Deficits in N-methyl-d-aspartate-type (NMDAR) function contribute to symptoms and cognitive dysfunction in schizophrenia. The efficacy of NMDAR agonists in the treatment of persistent symptoms of schizophrenia has been variable, potentially reflecting limitations in functional target engagement. We recently demonstrated significant improvement in auditory mismatch negativity (MMN) with once-weekly treatment with d-serine, a naturally occurring NMDAR glycine-site agonist. This study investigates effects of continuous (daily) NMDAR agonists in schizophrenia/schizoaffective disorder. Primary analysis was on MMN after double-blind crossover (60mg/kg/d, n=16, 6weeks) treatment with d-serine/placebo. Secondary measures included clinical symptoms, neurocognition, and the effects of open-label (30-120mg/kg/d, n=21) d-serine and bitopertin/placebo (10mg, n=29), a glycine transport inhibitor. Double-blind d-serine treatment led to significant improvement in MMN frequency (p=0.001, d=2.3) generation and clinical symptoms (p=0.023, d=0.80). MMN frequency correlated significantly with change in symptoms (r=-0.63, p=0.002) following co-variation for treatment type. d-Serine treatment led to a significant, large effect size increase vs. placebo in evoked α-power in response to standards (p=0.036, d=0.81), appearing to normalize evoked α power relative to previous findings with controls. While similar results were seen with open-label d-serine, no significant effects of bitopertin were observed for symptoms or MMN. These findings represent the first randomized double-blind placebo-controlled study with 60mg/kg d-serine in schizophrenia, and are consistent with meta-analyses showing significant effects of d-serine in schizophrenia. Results overall support suggest that MMN may have negative, as well as positive, predictive value in predicting efficacy of novel compounds. Clinicaltrials.gov: NCT00322023/NCT00817336 (d-serine); NCT01116830 (bitopertin).


Systematic review and meta-analysis: Artificial intelligence for the diagnosis of gastric precancerous lesions and Helicobacter pylori infection.
The endoscopic diagnosis of Helicobacter-pylori(H.pylori) infection and gastric precancerous lesions(GPL), namely atrophic-gastritis and intestinal-metaplasia, still remains challenging. Artificial intelligence(AI) may represent a powerful resource for the endoscopic recognition of these conditions. To explore the diagnostic performance(DP) of AI in the diagnosis of GPL and H.pylori infection. A systematic-review was performed by two independent authors up to September 2021. Inclusion criteria were studies focusing on the DP of AI-system in the diagnosis of GPL and H.pylori infection. The pooled accuracy of studies included was reported. Overall, 128 studies were found (PubMed-Embase-Cochrane Library) and four and nine studies were finally included regarding GPL and H.pylori infection, respectively. The pooled-accuracy(random effects model) was 90.3%(95%CI 84.3-94.9) and 79.6%(95%CI 66.7-90.0) with a significant heterogeneity[I2=90.4%(95%CI 78.5-95.7);I2=97.9%(97.2-98.6)] for GPL and H.pylori infection, respectively. The Begg's-test showed a significant publication-bias(p = 0.0371) only among studies regarding H.pylori infection. The pooled-accuracy(random-effects-model) was similar considering only studies using CNN-model for the diagnosis of H.pylori infection: 74.1%[(95%CI 51.6-91.3);I2=98.9%(95%CI 98.5-99.3)], Begg's-test(p = 0.1416) did not show publication-bias. AI-system seems to be a good resource for an easier diagnosis of GPL and H.pylori infection, showing a pooled-diagnostic-accuracy of 90% and 80%, respectively. However, considering the high heterogeneity, these promising data need an external validation by randomized control trials and prospective real-time studies.


[Schauta-Amreich expanded total vaginal excision in cervix cancer in relation to historical development].
After a historical outlook on the development of radical vaginal hysterectomy, our own results and complications in 51 cases of stages I and II during the years 1968-1983 are reported. The 5-year survival rate was 98.04% with no primary mortality.


A prospective controlled evaluation of combined pelvic radiotherapy and methanol extraction residue of BCG (MER) for locally unresectable or recurrent rectal carcinoma.
Forty-four patients with unresectable primary, residual, or recurrent colorectal carcinoma confined to the pelvis were randomized to treatment with split course megavoltage radiotherapy alone (5,000 rad given over 7 weeks) or in combination with the intradermal administration of the methanol extraction residue of BCG (MER) over an eight-month period. No improvement was observed in frequency of symptomatic palliation, interval to progression, or survival among patients receiving MER. Furthermore, there was no evidence of enhanced immunological status in patients receiving MER as compared to those receiving radiation alone. Although temporary pain relief was seen in 94% of patients with pretreatment pelvic or perineal pain, 37 patients (84%) have experienced subsequent progressive malignant disease. Regional recurrences within the radiotherapy port were observed in 28 of 31 patients who were evaluable for analysis of pattern of sites of initial progression. Eleven of the 28 patients with local failure also had distant metastasis at the time of tumor progression. There was no discernible clinical value associated with MER treatment in combination with radiotherapy as employed in this study. The high frequency of pelvic recurrence following radiotherapy at the dose and schedule we employed highlights the need for more effective treatment strategies for this group of patients.


Roles of hydrophobic and hydrophilic fractions of dissolved organic matter in sorption of ketoprofen to biochars.
Hydrophobic acid (HoA) and hydrophilic neutral (HiN) are two major fractions of dissolved organic matter (DOM). Their role in the sorption of ketoprofen (KTP) to wheat straw-derived biochars pyrolyzed at 300 °C (WS300) and 700 °C (WS700) was investigated to further probe the mechanisms responsible. WS700 has much higher pore volume and specific surface area (SSA) than WS300. Loading of HoA and HiN resulted in surface coverage of biochars. HoA with larger molecular size led to more pore blockage of biochars than HiN. Higher HoA binding affinity also caused a stronger competition with KTP on biochars. These factors reduced the accessibility of sorption sites for KTP, and significantly inhibited KTP sorption to biochar of lower SSA (i.e., WS300) by HoA. Water solubility (Sw) of KTP was slightly enhanced (3%) in the presence of HoA. In contrast, the presence of HiN reduced (22%) Sw of KTP. The decreased Sw of KTP by HiN exerted a more dominant influence than its competitive and loading effects, thus led to apparent enhanced sorption of KTP, especially to biochar of higher SSA (i.e., WS700). The results demonstrated the diverse effects of HoA and HiN on KTP sorption, which is helpful in understanding pharmaceutical-DOM-biochar interactions and environmental behaviors of pharmaceuticals.


Hyaluronan-based antiadhesive membrane has no major effect on intraperitoneal growth of colonic tumour cells.
A relationship between post-surgical adhesion formation and peritoneal tumour implantation has been proposed. Hyaluronan (HA)-based agents reduce adhesion formation, but the effect on peritoneal tumour is not established. This study investigated the influence of a HA-containing agent on intraperitoneal tumour in an experimental model. 66 Balb/c mice underwent laparotomy and damage was inflicted to the parietal peritoneum. The animals were randomized into five groups. Groups 1 and 2 received HA-carboxymethylcellulose bioresorbable membrane and no treatment, respectively. Mice in groups 3-5 were injected intraperitoneally with 10(5) colon 26-B cells after the laparotomy. Treatment consisted of HA membrane, no HA agent and placement of HA membrane on the non-traumatized peritoneal wall, respectively. Animals were killed after 14 days; adhesions were scored in groups 1 and 2, and the tumour mass in groups 3-5. 45 Wag/Rij rats underwent the same procedures and treatment as mice in groups 3-5. In rats, 10(6) CC-531 cells were injected. Rats were killed after 3 weeks and the tumour mass was scored. HA membrane resulted in a significant reduction of adhesions, but had no major effect on the intraperitoneal tumour mass in mice and rats. HA-carboxymethylcellulose bioresorbable membrane has no major effect on intraperitoneal tumour implantation and growth in an experimental model.


Structural and functional characterization of the first intracellular loop of human thromboxane A2 receptor.
The conformation of a constrained peptide mimicking the putative first intracellular domain (iLP1) of thromboxane A(2) receptor (TP) was determined by (1)H 2D NMR spectroscopy. Through completed assignments of TOCSY, DQF-COSY, and NOESY spectra, a NMR structure of the peptide showed a beta-turn in residues 56-59 and a short helical structure in the residues 63-66. It suggests that residues 63-66 may be part of the second transmembrane domain (TM), and that Arg60, in an exposed position on the outer surface of the loop, may be involved in signaling through charge contact with Gq protein. The sequence alignment of Lys residue in the same position of other prostanoid receptors mediates different G protein couplings, suggesting that the chemical properties of Arg and Lys may also affect the receptor signaling activity. These hypotheses were supported by mutagenesis studies, in which the mutant of Arg60Leu completely lost activity in increasing intracellular calcium level through Gq coupling, and the mutant of Arg60Lys retained only about 35% signaling activity. The difference between the side chain functions of Lys and Arg in effecting the signaling was discussed.


High IL-7 levels in the bone marrow microenvironment mediate imatinib resistance and predict disease progression in chronic myeloid leukemia.
Chronic myeloid leukemia (CML) is a three-stage myeloproliferative disease caused by translocation between chromosomes 9 and 22. Although tyrosine kinase inhibitors (TKI) are highly effective in the treatment of CML, numerous clinical trials have shown that many patients become refractory or drug resistance, especially those in the blastic crisis of CML. The molecular mechanisms underlying CML, however, remain poorly understood. In the present study, we used a coculture model to address possible mechanisms underlying the involvement of bone marrow microenvironment in the drug resistance of CML. Our data show that interleukin-7(IL-7) levels in the bone marrow of CML patients in blastic crisis are significantly higher than those of both healthy persons and CML patients in chronic and accelerated phases. The increased IL-7 was secreted by mesenchymal stem cells (MSC) in the bone marrow, which may protect leukemic cells from apoptosis induced by imatinib through JAK1/STAT5 signaling pathway. Our findings suggest that therapeutic strategies IL-7 signaling pathway may represent a promising approach for improving CML therapy, especially for patients in blastic crisis.


Teat canal closure in non-lactating heifers and its association with udder health in the consecutive lactation.
Prevention of heifer mastitis is a key element in preventing mastitis. Since pathogenesis of heifer mastitis is not fully understood yet, combating it is arduous. The goal of this study was to examine whether the premature loss of the keratin plug of the teat canal represents an important risk factor for the development of heifer mastitis. 84 dairy heifers (German Holstein) from six high-yielding dairy herds in Northern Germany were examined between March 2005 and June 2006. Each quarter was examined clinically at least three times before calving. If the teat canal of a quarter was open, secretion samples were collected for bacteriological analysis. After calving, four quarter samples were collected during the first lactation. A rapid increase of the proportion of open teat canals was detected in the preparturition period. No teat canals were open till 80 days before parturition, while 60% of the teat canals were open at 60 days before parturition. A time-scheduled infection pattern was observed: during the days 90-61, 60-31, and 30-0 before calving, skin inhabitants (coagulase-negative staphylococci, coryneform bacteria), cow-related, and environment-related microorganisms prevailed, respectively. A total of 77% of intramammary infections encountered at parturition had established previously. No significant association between the duration of open teat canals before calving and the udder health post partum was found. However, the incidence of clinical mastitis during first lactation was influenced largely by the duration of infection ante partum and the mastitis pathogen involved. This study shows that a high proportion of teat canals already opens several months before calving and that opening of the teat canal before calving is an important factor in the aetiology of heifer mastitis.


Prostate-Specific Antigen Screening in Transgender Patients.
Approximately 0.4-1.3% of the worldwide population is transgender. Although the exact prevalence is unknown, there is an increase in open identification as transgender. Among transgender women (TW), the prostate is retained even after gender-affirmation surgery, thus necessitating ongoing screening for prostate cancer (CaP). However, little is known about CaP screening in this population. To assess our current understanding of CaP incidence and prostate-specific antigen (PSA) screening in TW. We performed a nonsystematic narrative review of all PubMed publications through June 2022 according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. Given the limited primary research on this subject, case reports were also included. Studies were reviewed to understand PSA screening practices and reports of CaP in this population, as applicable. There is no consensus regarding PSA screening in TW from any of the major societies, and TW are largely absent from guidelines. Case report data suggest that TW with CaP may have more aggressive disease, and these cancers may have been pre-existing prior to present before gender-affirming hormone therapy (GAHT) or be castrate-resistant. We are in the infancy of our understanding of PSA screening in TW. Important avenues for future research include understanding the risks/benefits of PSA screening in TW, how best to mitigate potential negative psychological effects of PSA screening in TW, establishing baseline PSA values for those on GAHT (and determining what values should be considered "elevated"), establishing when to initiate PSA screening for those on GAHT, and establishing the accuracy of biomarkers for those undergoing GAHT. We examined patterns of prostate cancer screening for transgender women. Little is known about prostate cancer incidence or screening in this population. Additional research is needed to establish guidelines for screening in this population.


DNA -based hydrogels for high-performance optical biosensing application.
Analyte-sensitive DNA-based hydrogels find multiple applications in the field of biosensors due to their adaptable nature. Here, the design of DNA-based hydrogel and its application as sensing platform for the detection of a specific target sequence are presented. DNA-functionalized hydrogel structures were formed via a free radical co-polymerization process. A simple one-step probe immobilization procedure is reported: DNA probe molecules are added to the photoactive polymer mixture, dispensed onto a solid support, or a mold, and covalently attached while the hydrogel is formed through UV light exposure. Such hydrogels can be synthesized with desired recognition ability through the selection of a certain nucleotide sequence. Here we show the application of DNA-based hydrogel to detect the target with high performance in fluorescence microarray format and, additionally, to fabricate holographic surface relief gratings for label-free sensing assays.


Prevalence and associated influential factors of mental health problems among Chinese college students during different stages of COVID-19 pandemic: A systematic review.
This systematic review aims to take China as an example to determine the prevalence of mental health problems and associated influential factors of college students in different stages of the COVID-19 pandemic and provide a reference for effective intervention in the future. A systematic search was conducted on PubMed, Web of Science, Scopus, Science Direct, and Google scholar. A total of 30 articles were included. 1,477,923 Chinese college students were surveyed. In the early stage, the prevalence rates of depression, anxiety, stress, and PTSD ranged from 9.0% to 65.2%, 6.88%-41.1%, 8.53%-67.05%, and 2.7%-30.8%, respectively. Major risk factors were being a female, a medical student, isolation or quarantine, having family members or friends infected with COVID-19, and challenges of online learning. During the normalization stage, depression, anxiety, and insomnia prevalence rates ranged from 8.7% to 50.2%, 4.2%-34.6%, and 6.1%-35.0%, respectively. The main risk factors were self-quarantined after school reopening, regular taking temperature, and wearing face masks. The prevalence rates of mental health problems and associated influential factors unveiled in both stages showed that the students' mental health status was greatly affected. Therefore, a combination of efforts from the government, universities, and families or communities is highly needed to alleviate the mental health sufferings of students.


Functional toxicity and tolerance patterns of bioavailable Pd(II), Pt(II), and Rh(III) on suspended Saccharomyces cerevisiae cells assayed in tandem by a respirometric biosensor.
Toxicological implications of exposure to bioavailable platinum group metals, here Pd, Pt, and Rh, are still to be clarified. This study obtained by a biosensor-based method preliminary information on potential effects on cellular metabolism as well as on possible tolerance mechanisms. Aerobic respiration was taken as the toxicological end point to perform tandem tests, namely functional toxicity test and tolerance test. Cells were suspended in the absence of essential constituents for growth. The dose-response curves obtained by exposure (2 h) to the metals (nanogram per gram range) suggested the same mechanisms of action, with Rh showing the greatest curve steepness and the lowest EC50 value. Conservative (95% lower confidence interval) EC10 values were 187, 85 and 51 ng g(-1) for Pt, Pd, and Rh respectively. Tolerance patterns were tested during the same runs. The full tolerance obtained after 12 h of exposure to each metal suggested mitochondrial inhibition of aerobic respiration as a target effect. The hazard rating of the metals in the tolerance test changed in the Rh EC50 range, where Rh showed the lowest toxicity. The observed tolerance might suggest a protective mechanism such as metallothionein induction at concentrations around the EC50 values. The performance of the bioassay was satisfactory, in terms of the limit of detection, repeatability, reproducibility, roboustness, sensibility, and stability; the method's critical uncertainty sources were identified for improvements.


Release of endogenous histamine in the hypothalamus of anaesthetized cats and conscious, freely moving rabbits.
The hypothalamus of anaesthetized cats and conscious, freely moving rabbits was superfused with CSF through double-walled, push-pull cannulae and the release of endogenous histamine was determined in the superfusates by a radioenzymatic assay. In the posterior hypothalamic area of the anaesthetized cat, the rate of release of endogenous histamine varied rhythmically; phases of high rate of release appeared at 60 min cycles. The release of histamine was increased by electrical stimulation of the superfused area, as well as by hypothalamic superfusion with potassium-rich CSF. In the conscious rabbit, the anterior hypothalamic area and the posterior hypothalamic nucleus were superfused simultaneously. In both regions, the resting release of histamine varied rhythmically at approximately 70 min cycles. Phases of high or low-rate of release in the anterior hypothalamic area coincided with the corresponding phases in the posterior hypothalamic nucleus. The rhythmic release of endogenous histamine in the hypothalamus, as well as the ability of depolarizing stimuli to enhance the release of the amine support the idea that histamine acts as a neurotransmitter in the central nervous system.


Drug insight: emerging new drugs in the treatment of myelodysplastic syndromes.
Myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic stem cell disorders. Although the currently used classification schemes and prognostic algorithms, which are based predominantly on morphologic assessment of blood and marrow smears, have been shown to be valid for defining disease subgroups, they do not take into consideration the significant biological diversity of MDS. As the numerous pathophysiologic pathways that are involved in MDS are being unraveled, new molecular targets are being identified. Novel and targeted therapeutic agents, including inhibitors of farnesyltransferases and receptor tyrosine kinases, more potent thalidomide analogs and epigenetic therapies, have produced encouraging results and might offer durable benefits to patients with MDS. This review intends to provide a concise report on some of the most up-to-date therapies being investigated in MDS.


Thymic changes as a contributing factor in the increased susceptibility of old Albino Oxford rats to EAE development.
The study was aimed to examine putative contribution of thymic involution to ageing-associated increase in susceptibility of Albino Oxford (AO) rats to the development of clinical EAE, and vice versa influence of the disease on the progression of thymic involution. To this end we examined (i) the parameters of thymocyte negative selection efficacy, the thymic generation of CD4+CD25+Foxp3+ T regulatory cells (Tregs) and thymic capacity to instruct/predetermine IL-17-producing T-cell differentiation, and thymopietic efficacy-associated accumulation of "inflammescent" cytotoxic CD28- T cells in the periphery, and (ii) the key underlying mechanisms in young and old non-immunised AO rats and their counterparts immunised for EAE (on the 16th day post-immunisation when the disease in old rats reached the plateau) using flow cytometry analysis and/or RT-qPCR. It was found that thymic involution impairs: (i) the efficacy of negative selection (by affecting thymocyte expression of CD90, negative regulator of selection threshold and the expression of thymic stromal cell integrity factors) and (ii) Treg generation (by diminishing expression of cytokines supporting their differentiation/maturation). Additionally, the results suggest that thymic involution facilitates CD8+ T-cell differentiation into IL-17-producing cells (previously linked to the development of clinical EAE in old AO rats). Furthermore, they confirmed that ageing-related decrease in thymic T-cell output (as indicated by diminished frequency of recent thymic emigrants in peripheral blood) resulted in the accumulation of CD28- T cells in peripheral blood and, upon immunisation, in the target organ. On the other hand, the development of EAE (most likely by increasing circulatory levels of proinflammatory cytokines) contributed to the decline in thymic output of T cells, including Tregs, and thereby to the progression/maintenance of clinical EAE. Thus, in AO rats thymic involution via multi-layered mechanisms may favour the development of clinically manifested autoimmunity, which, in turn, precipitates the thymus atrophy.


Spectral analysis of hippocampal unit train in relation to hippocampal EEG.
Sampling and analysis programs are implemented on a microcomputer for the computation of autopower, coherence and phase spectra of unit train and EEG. Application to the hippocampus reveals that both theta and fast activity in the EEG are correlated with different phase relationships with unit activity. The estimate of coherence and phase spectra of unit-EEG relationship has not been reported before and is unique for the present method.


Effects of dopamine on pial arteriolar diameter and CSF prostanoid levels in piglets.
We examined effects of topically applied dopamine on pial arteriolar diameter and CSF prostanoid levels in newborn pigs. Vascular responses were determined using the closed cranial window technique and intravital microscopy, and prostanoids were determined by radioimmunoassay. Topical application of dopamine did not change arteriolar diameter at 10(-7)-10(-5) M, but constricted arterioles at 10(-4) (16%) and 10(-3) M (30%). Intravenous administration of indomethacin (5 mg/kg) did not alter this constriction. In addition, CSF prostanoid levels did not increase in response to application of dopamine except for a modest increase of prostaglandin E2 at 10(-3) M. We conclude that dopamine is a constrictor at high doses of piglet pial arterioles and that this response is not modified by endogenous prostanoids.


Effect of exercise on human arterial and regional venous plasma concentrations of prostaglandin E.
Healthy male volunteers underwent catheterization of a brachial artery and subclavian, hepatic, renal, and femoral veins. Blood was sampled simultaneously from all catheters, at rest as well as during supine leg exercise at 130 W. Plasma PGE were extracted and purified, using silicic acid chromatography, and subsequently quantified, using RIA. At rest no release or uptake of PGE was observed in the arm, the splanchnic region, or the leg, but in the kidney an uptake was noted. During exercise a significant release of PGE developed in the arm and in the leg. The data support the hypothesis that vascular PGs play a role in the local adaptation of the circulatory system to exercise.


Generation and application of endogenously floxed alleles for cell-specific knockout in zebrafish.
The zebrafish is amenable to a variety of genetic approaches. However, lack of conditional deletion alleles limits stage- or cell-specific gene knockout. Here, we applied an existing protocol to establish a floxed allele for gata2a but failed to do so due to off-target integration and incomplete knockin. To address these problems, we applied simultaneous co-targeting with Cas12a to insert loxP sites in cis, together with transgenic counterscreening and comprehensive molecular analysis, to identify off-target insertions and confirm targeted knockins. We subsequently used our approach to establish endogenously floxed alleles of foxc1a, rasa1a, and ruvbl1, each in a single generation. We demonstrate the utility of these alleles by verifying Cre-dependent deletion, which yielded expected phenotypes in each case. Finally, we used the floxed gata2a allele to demonstrate an endothelial autonomous requirement in lymphatic valve development. Together, our results provide a framework for routine generation and application of endogenously floxed alleles in zebrafish.


The infracolic approach to pancreatoduodenectomy for large pancreatic head tumours invading the colon.
Tumours arising from the head of the pancreas can invade both the proximal transverse colon and its mesocolon. At laparoscopy, this may be considered a contraindication to proceeding to pancreatoduodenectomy. However, in some patients, pancreatoduodenectomy can still be performed with an R0 resection using an en-bloc resection technique by an infracolic approach. This technique relies on the infracolic control of the superior mesenteric vein (SMV) and is based on the presence of a normal fat cuff around the superior mesenteric artery (SMA) on pre-operative imaging. The dissection is maintained along the adventitial plane of the SMA. Pancreatoduodenectomy is performed in conjunction with en-bloc resection of the transverse colon. In the event of tumour invading the SMV, this is also resected en-bloc with the pancreatic head and transverse colon. We reviewed all such cases performed at our institution between April 2004 and April 2009. This technique was attempted in eleven patients. In two patients, the procedure had to be abandoned because of unexpected SMA encasement by tumour. In the remaining nine patients this procedure was carried out successfully. In this paper, the infracolic approach to pancreatoduodenectomy, and the associated limitations, are described in detail. The infracolic technique may be used to deal with large pancreatic head tumours and all pancreatic surgeons should be familiar with this technique. In the absence of metastatic disease, large pancreatic head tumours involving the colon can be resected en-bloc with the pancreatic head, as long as the SMA is not encased by the tumour.


Adverse birth outcomes in Guangdong province, China, 2014-2017: a spatiotemporal analysis of 2.9 million births.
Adverse birth outcomes pose a great threat to the public health and bring a heavy burden of disease in China. A comprehensive examination of the temporal and spatial trends of preterm birth (PTB), low birth weight (LBW) and small for gestational age (SGA) epidemics can provide some elementary information for subsequent aetiological and epidemiological studies. This study aimed to characterise the spatiotemporal features of PTB, LBW and SGA based on a large cohort of live births in China. Spatiotemporal descriptive analysis was performed in Guangdong province, China, from 2014 to 2017. Data involving 2 917 098 live births in Guangdong province, China from 2014 to 2017 was collected from Guangdong Birth Certificate System. Information was collected, including the date of birth, gestational age in week, birth weight, sex of the infant, age of the mother and registered residence of the mother. The estimated rate of PTB, LBW and SGA was 4.16%, 4.14% and 12.86%, respectively. For temporal trends, the rates of PTB, LBW and SGA showed seasonal fluctuations, especially for LBW and SGA. In addition, there were regional differences in the rates of PTB, LBW and SGA between the Pearl River Delta and Non-Pearl River Delta regions. From 2014 to 2017, the high rates of PTB and LBW expanded from the Pearl River Delta region to the Non-Pearl River Delta regions. However, compared with the Pearl River Delta region, the rate of SGA was higher in the Non-Pearl River Delta regions on the whole. The findings of this study contribute to the understanding of the aetiology and epidemiology of PTB, LBW and SGA in south China.


Annual Medical Costs of Swedish Patients with Type 2 Diabetes Before and After Insulin Initiation.
Although insulin is one of the most effective interventions for the treatment of type 2 diabetes, its disadvantages incur substantial medical cost. This study was designed to evaluate the medical costs of Swedish type 2 diabetic patients initiating insulin on top of metformin and/or sulfonylurea (SU), and to evaluate if costs before and after insulin initiation differ for patients where insulin is initiated above or below the recommended glycosylated hemoglobin (HbA1c) level (7.5%). This was a register-based retrospective cohort study in which patients were identified from the Sörmland county council diabetes register. Patients being prescribed at least one prescription of metformin and/or SU from 2003 to 2010, and later prescribed insulin, were included. One hundred patients fulfilled the inclusion criteria and had at least 1 year of follow-up. The mean age was 61 years and 59% of patients were male. Mean time since diagnosis was 4.1 years, and since initiation of insulin was 2.2 years. The mean HbA1c level at index date was 8.0%. Total mean costs for the whole cohort were SEK 17,230 [standard deviation (SD) 17,228] the year before insulin initiation, and SEK 31,656 (SD 24,331) the year after insulin initiation (p < 0.0001). When stratifying by HbA1c level, patients with HbA1c <7.5% had total healthcare costs of SEK 17,678 (SD 12,946) the year before the index date and SEK 35,747 (SD 30,411) the year after (p < 0.0001). Patients with HbA1c levels ≥7.5% had total healthcare costs of SEK 16,918 (SD 19,769) the year before the index date and SEK 28,813 (SD 18,779) the year after (p < 0.0001). Despite the small sample size, this study demonstrates that mean annual medical costs almost double the year after patients are initiated on insulin. The costs increased the year after insulin initiation, regardless of the HbA1c level at initiation of insulin, and the largest increase in costs were due to increased filled prescriptions.


Preparation and properties of composite cellulose fibres with the addition of graphene oxide.
The paper presents the results of a study on the preparation of cellulose-based composite fibres (CEL) with graphene oxide addition (GO). Composite fibres (GO/CEL) were prepared via the wet spinning method from CEL solutions in 1-ethyl-3-methylimidazolium acetate (EMIMAc) that contained a nano-addition of GO dispersion in N,N-dimethylformamide (DMF). The GO contents of the composite fibres were 0, 0.21, 0.50, 0.98, and 1.97 % w w. The fibres were coagulated in two solvents: distilled water and methanol. The results demonstrated that the amount of GO additive and the type of coagulant significantly impact the physicochemical, mechanical and structural properties of the CEL and GO/CEL fibres. The use of distilled water in a coagulation bath causes a degree of crystallinity of 31.0-40.8 % (WAXS) and a shift in the thermal decomposition temperature (by approximately 19 °C) towards higher temperatures (TGA). The results demonstrate improvements in the mechanical properties of the GO/CEL fibres, which were at the level of 9.43-14.18 cN/tex. In addition, the GO/CEL fibres exhibit satisfactory GO dispersion throughout their volume.


Epidermoid cyst of testis: a report of 3 cases.
We report 3 cases of simple epidermoid cyst of the testis. These tumors often are mistaken clinically for malignancy. Conservative surgical treatment with preservation of the testis is desirable when preoperative ultrasound reveals a well demarcated cystic nodule confirmed by histological frozen sections.


The relationship between depression and sexual function in menopause period.
Menopause is a physiological process that is lived universally by every middle age woman. This study has been made with the aim of determining the relation between depression situation and sexual function of women in menopause period. This study was made with 300 women in menopause who applied to Akdeniz University Research and Application Hospital on January 2007. Study used socio-demographic data descriptive survey form, Beck Depression Inventory and sexual function scale as data collection tool. Data were collected by researchers in face-to-face interviews. In the study it was found that age and marriage duration of women could reduce sexual function. Depression was determined in 29.3% of women and sexual dysfunction in 65% of women. Significant negative relation was found between sub-dimension of sexual function scale of women vaginal slickness, orgasm, pain, total sexual dysfunction and depression point. In the study it was determined that while depression points increased with menopause, sexual function reduced and with the increase of depression point, sexual dysfunction increased too. Qualitative studies must be made that will examine emotional situations and sexual life of women.


Pharmacokinetics and pharmacodynamics of outpatient intravenous antimicrobial therapy.
Outpatient intravenous antimicrobial therapy has been widely accepted over the past decade. Knowledge of both the pharmacokinetics of antimicrobials and the pharmacodynamics predictive of antimicrobial efficacy enables one to design reasonable outpatient intravenous regimens for most agents. This article summarizes current knowledge of the pharmacokinetics and pharmacodynamics of agents commonly used in outpatient intravenous treatment regimens.


Identification and development of a novel 5-gene diagnostic model based on immune infiltration analysis of osteoarthritis.
Osteoarthritis (OA), which is due to the progressive loss and degeneration of articular cartilage, is the leading cause of disability worldwide. Therefore, it is of great significance to explore OA biomarkers for the prevention, diagnosis, and treatment of OA. The GSE129147, GSE57218, GSE51588, GSE117999, and GSE98918 datasets with normal and OA samples were downloaded from the Gene Expression Omnibus (GEO) database. The GSE117999 and GSE98918 datasets were integrated, and immune infiltration was evaluated. The differentially expressed genes (DEGs) were analyzed using the limma package in R, and weighted gene co-expression network analysis (WGCNA) was used to explore the co-expression genes and co-expression modules. The co-expression module genes were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. A protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and hub genes were identified by the degree, MNC, closeness, and MCC algorithms. The hub genes were used to construct a diagnostic model based on support vector machines. The Immune Score in the OA samples was significantly higher than in the normal samples, and a total of 2313 DEGs were identified. Through WGCNA, we found that the yellow module was significantly positively correlated with the OA samples and Immune Score and negatively correlated with the normal samples. The 142 DEGs of the yellow module were related to biological processes such as regulation of inflammatory response, positive regulation of inflammatory response, blood vessel morphogenesis, endothelial cell migration, and humoral immune response. The intersections of the genes obtained by the 4 algorithms resulted in 5 final hub genes, and the diagnostic model constructed with these 5 genes showed good performance in the training and validation cohorts. The 5-gene diagnostic model can be used to diagnose OA and guide clinical decision-making.


Integrated ocean management for a sustainable ocean economy.
The rapidly evolving ocean economy, driven by human needs for food, energy, transportation and recreation, has led to unprecedented pressures on the ocean that are further amplified by climate change, loss of biodiversity and pollution. The need for better governance of human activities in the ocean space has been widely recognized for years, and is now also incorporated in the United Nations Sustainable Development Goals. Even so, many challenges relating to the implementation of existing governance frameworks exist. Here, we argue that integrated ocean management (IOM) should be the key overarching approach-building upon and connecting existing sectoral governance efforts-for achieving a sustainable ocean economy. IOM is a holistic, ecosystem-based and knowledge-based approach that aims to ensure the sustainability and resilience of marine ecosystems while integrating and balancing different ocean uses to optimize the overall ocean economy. We discuss examples of IOM in practice from areas where preconditions differ substantially, and identify six universal opportunities for action that can help achieve a sustainable ocean economy.


Rapid visible-near infrared (Vis-NIR) spectroscopic detection and quantification of unripe banana flour adulteration with wheat flour.
Unripe banana flour is a premium nutritious product with a potential to curb degenerative diseases through resistant starch and gluten free traits, however, with scant techniques to monitor adulteration practices. The objective of the present study was to determine the efficacy of visible-near infrared spectroscopy (Vis-NIR) spectroscopy (Vis-NIRS) in the detection and quantification of unripe banana flour adulteration with wheat flour. To do this, simulated adulteration of a composite banana flour was performed with different levels of wheat flour, in intervals of 20 g kg-1, ranging from 0 to 800 g kg-1. Each level was acquired in duplicate giving a total of 82 samples. Vis-NIR spectral data was acquired using a portable F-750 spectrometer in the range 447-1005 nm. Spectral data was analysed chemometrically using principle components analysis and partial least squares regression (PLSR), with 41 samples used as a calibration set and 41 for validation. The first two principal components accounted for 95% of spectral data variation, revealing five distinct clusters related to 0 g kg-1, 20-200 g kg-1, 220-400 g kg-1, 420-600 g kg-1 and 620-800 g kg-1 adulterated samples. The best PLSR model to predict wheat flour adulteration degrees in unripe banana flour was obtained using 2nd derivative Savitzky-Golay (19-point smoothing, 2nd order polynomial), showing the highest Rc 2 (0.991); Rp 2 (0.993); RPD (12.021) and the lowest RMSEC (2.226 g kg-1) and RMSEP (1.993 g kg-1) values. The obtained Vis-NIRS PLSR models therefore demonstrated the technology novelty in monitoring unripe banana flour quality by the processing industries and in retail markets during product verification.


Tumour blood flow following local ultrasound heating computed from thermal clearance curves.
Thermal clearance curves following termination of ultrasound-induced hyperthermia in human mammary carcinomas implanted into the flanks of nude rats were studied. They were found to be monoexponential in form, both with and without blood flow. From the difference between the inverse time constants with and without flow, the tumour blood flow rate could be calculated. Blood flow was found to increase with very short exposure times at the therapeutic hyperthermia temperature and subsequently decrease as the exposure time increased. A higher therapeutic hyperthermia temperature augmented this effect.


Sucrose phosphorylase from Lactobacillus reuteri: Characterization and application of enzyme for production of 2-O-α-d-glucopyranosyl glycerol.
The enzymatic synthesis of 2-O-α-d-glucopyranosyl-glycerol (2-αGG) by transglycosylation activity of sucrose phosphorylase (SPase) is a promising method for 2-αGG manufacturing. However, there are only a few SPases available for 2-αGG production. Here, we report on the characterization and application of SPase from Lactobacillus reuteri (LrSPase). The results of transglycosylation properties assay showed that LrSPase was a potential glycerol glycosylating tool with high activity at pH 8.0 and 45 °C. And the transglycosylation activity of LrSPase was seriously inhibited by Fe3+, Zn2+ and Cu2+. Moreover, the result of substrate specificity assay showed LrSPase was able to catalyze the transglycosylation of 13 phenolic compounds. To produce commercially relevant concentrations of 2-αGG, we have developed a practical, efficient and scalable process for 2-αGG production using sucrose batch-feeding strategy by whole-cell catalyst. The maximum titer of 2-αGG was 237.68 g L-1 with a productivity of 23.39 mM h-1 and the molar conversion rate of glycerol reached 62.38%. To the best of our knowledge, this is the highest 2-αGG production level by using only SPase to synthesize 2-αGG until now. This study provides an effective way for industrial production of 2-αGG.


How to build an "active" patient? The work of AIDS associations in France.
"What is an "active" patient?" is a question that arises in most medicine and illness-related social science research. This article examines the normative work carried out by AIDS associations in France to define an "active" patient in healthcare and research. While the fight against AIDS is often presented as being homogenous, we look at the diversity of opinion between different associations (Aides, Act Up-Paris, Actions Traitements and Positifs). We find four different cases: the patient as manager of his illness, the empowerment of patients, the science-wise patient and the experimenter. Systematic comparison of these cases shows that these perceptions of the "active" patient, in terms of the same pathology, are based upon different ways of seeing: the nature of the relationships between the different types of knowledge of the illness (scientific knowledge, clinical knowledge, experience of the illness) and the distribution of roles and powers among the various actors in the healthcare system (the government, pharmaceutical companies, the medical profession, the patients). This article highlights the historical dynamics which allow us to have a better understanding of these differences, especially the major distinction between two generations of associations, which adopted different positions with regard to their public identity.


Crosstalk of cholinergic pathway on thyroid disrupting effects of the insecticide chlorpyrifos in zebrafish (Danio rerio).
Chlorpyrifos is a widely used organophosphate insecticide and ubiquitously detected in the environment. However, little attention has been paid to its endocrine disrupting effect to non-target organisms. In the present study, zebrafish was exposed to 13 and 65 μg/L of chlorpyrifos for 7 and 10 days to determine the induced neurotoxicity and the alteration of thyroid metabolism. The 120 h LC50 and LC10 of chlorpyrifos was estimated as 1.35 mg/L and 0.62 mg/L based on the acute embryo toxicity assay, respectively. The acetylcholinesterase (AChE) inhibitory was detected by 13 μg/L chlorpyrifos and could be reversed by the co-exposure of 100 and 1000 μg/L anticholinergic agent atropine. For thyroid hormone level, 13 and 65 μg/L of chlorpyrifos induced increased free T3 levels in 10 dpf (days post-fertilization). The expression of thyroid related genes in 7 and 10 dpf exposed zebrafish were measured by the quantitative Real-Time PCR (qRT-PCR) assay. The mRNA expression of tshba, thrb, crhb, ttr, tpo, ugt1ab and slc5a5 had significant change. However, the alterations of thyroid hormone and mRNA expression could be partly rescued by the addition of atropine. The molecular docking of chlorpyrifos and T3 to the thyroid receptor β in zebrafish using homology modelling and CDOCKER procedures shown weaker binding ability of chlorpyrifos compared to T3. Therefore, we concluded that the disturbance of thyroid signaling in zebrafish might arise from the developmental neurotoxicity induced by chlorpyrifos.


Safety, humoral and cell-mediated immune responses to herpes zoster vaccine in subjects with diabetes mellitus.
To evaluate varicella zoster virus-specific cell-mediated immunity and humoral immunogenicity against the herpes zoster vaccine, which is licensed as the Live Varicella Vaccine (Oka Strain) in Japan, in elderly people with or without diabetes mellitus. A pilot study was conducted between May 2010 and November 2010 at Kitano Hospital, a general hospital in the city of Osaka in Japan. A varicella skin test, interferon-gamma enzyme-linked immunospot assay and immunoadherence hemagglutination tests were performed 0, 3, and 6 months after vaccination. Vaccine safety was also assessed using questionnaires for 42 days and development of zoster during the one-year observational period. We enrolled 10 healthy volunteers and 10 patients with diabetes mellitus aged 60-70 years. The live herpes zoster vaccine boosted virus-specific, cell-mediated and humoral immunity between elderly people, with or without diabetes. Moreover, no systemic adverse reaction was found. None of the study participants developed herpes zoster. The live herpes zoster vaccine was used safely. It effectively enhanced specific immunity to varicella zoster virus in older people with or without diabetes mellitus.


Tumor Tissue Analogs for the Assessment of Radioresistance in Cancer Stem Cells.
Over the years, radiotherapy-related research has been based on local tumor control as an experimental endpoint, yielding a wealth of data demonstrating the importance of cancer stem cells in tumor reoccurrence after radiotherapy. Literature is replete with experimental and clinical evidence that the cancer stem cell population in a tumor affects its radiocurability. An important consideration for radiotherapy is the microenvironmental stimuli in the CSC niche that results from factors such as hypoxia, extracellular matrix (ECM) elements and their intercellular interaction with non-stem cells and other cell types that prevail in the tumor milieu. In this chapter, we have described the methodology to develop in vitro 3D tumor models that incorporate these microenvironmental characteristics and design experiments that generate endpoints for understanding radioresistance in cancer stem cells.


Temperament and character in transsexuals.
The aim of this study was to evaluate personality in transsexuals. The Temperament and Character Inventory (TCI) profiles of 166 male-to-female (MF) and 88 female-to-male (FM) transsexuals were compared with those of a control group of males and females. MF and FM transsexuals scored significantly lower than males and females in RD4 (more independent) and C3 (more self-centeredness). MF transsexuals scored higher than males and females in HA4 (more fatigable), ST and ST3 (more spiritual acceptance), and lower in C5 (more opportunistic); moreover, they showed higher scores than males in RD1 (more sentimental) and lower than females in C (less cooperativeness). FM transsexuals scored lower than females in HA2 (more daring and confident), RD (less sentimental), and C5 (more opportunistic). Compared with FM, MF transsexuals scored higher on HA2 (more fearful), RD, RD1 (more sentimental), ST, ST2 and ST3 (more spiritual). All these differences were less than half a standard deviation except for C3. Data show that transsexuals and controls display a similar personality profile, even though there are some differential personality traits. Moreover, the personality profile of transsexuals was closer to the profile of subjects who shared their gender identity than those who shared their anatomical sex.


Effect of energy source on the efficiency of translational termination during cell-free protein synthesis.
We studied how the fidelity of translation termination is affected by the method of ATP regeneration during cell-free protein synthesis. During the in vivo expression of hEPO, whose termination is directed by the UGA codon, we found that substantial proportions of the translational products showed a larger molecular weight than expected. Similar results were obtained in a cell-free synthesis reaction using phosphoenol pyruvate (PEP) or 3-phosphoglycerate (3PG) for ATP regeneration. However, when the energy source was switched to creatine phosphate (CP), the readthrough of the UGA codon was completely repressed and only the target protein of the correct size was expressed in a high yield. To the best of our knowledge, this is the first report describing the relationship between the regeneration of nucleotide triphosphates and protein readthrough, and we also believe that the discovery would pave the way to the selective and efficient expression of target proteins in cell-free protein synthesis systems.


Mosquito Surveillance for West Nile Virus.
Identifying the mosquitoes responsible for transmitting human disease-causing pathogens is of critical importance for effective control of mosquito-borne outbreaks. West Nile virus is often transferred by adult female mosquitoes in the genus Culex, which deposit eggs in a variety of aquatic habitats throughout the world. Herein we describe several methodological approaches to monitor these species in nature, as well as offering details for data collection and analysis.


Carryover of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) from soil to plant and distribution to the different plant compartments studied in cultures of carrots (Daucus carota ssp. Sativus), potatoes (Solanum tuberosum), and cucumbers (Cucumis Sativus).
A vegetation study was carried out to investigate the carryover of Perfluorooctanoic Acid (PFOA) and Perfluorooctane Sulfonate (PFOS) from soil mixed with contaminated sewage sludge to potato, carrot, and cucumber plants. Analysis was done by liquid-extraction using acetonitrile with dispersive SPE cleanup and subsequent HPLC-MS/MS. In order to assess the transfer potential from soil, transfer factors (TF) were calculated for the different plant compartments: TF = [PFC](plant (wet substance))/[PFC](soil (dry weight)). The highest TF were found for the vegetative plant compartments with average values for PFOS below those for PFOA: cucumber, 0.17 (PFOS), 0.88 (PFOA); potato, 0.36 (PFOS), 0.40 (PFOA); carrot, 0.38 (PFOS), 0.53 (PFOA). Transfer of PFOA and PFOS into potato peelings (average values of TF: PFOA 0.03, PFOS 0.04) exceeded the carryover to the peeled tubers (PFOA 0.01, PFOS < 0.01). In carrots, this difference did not occur (average values of TF: PFOA 0.04, PFOS 0.04). Transfer of PFOS into the unpeeled cucumbers was low and comparable to that of peeled potatoes (TF < 0.01). For PFOA, it was higher (TF: 0.03).


Gynecologic Oncology fellowship recruitment in the virtual era: An evaluation of program websites and survey of applicant preferences.
Virtual Gynecologic Oncology fellowship recruitment has altered how candidates and programs exchange information. This study analyzes programs' web-based content and the priorities of fellowship candidates. Web-based materials of Gynecologic Oncology fellowship programs participating in the 2022 match were reviewed. An anonymous survey was emailed to applicants. Questions assessed importance of web-based materials on a Likert scale. Respondents were asked to rank factors from most to least important in their decisions to interview and rank programs. Of the 66 programs participating in the 2022 Gynecologic Oncology fellowship match, 62 (93.9%) had accessible websites. Over one-fourth (25.8%) of program websites did not list application requirements. Most (74.2%) websites contained requests for letters of recommendation, but fewer (48.4%) specified the preferred quantity or authorship. Residency in-service exam score requirement information was present on 61.3% of websites. Of 100 applicants invited to participate, 44 returned surveys (44% response rate). The median number of programs applied to was 60 (IQR 51-65). Web-based materials most important to candidates were application requirements and deadlines, letter of recommendation details, and in-service exam requirements. Interaction with faculty and program information received during interview days were among the most important factors in decisions to rank programs. Gynecologic Oncology fellowship applicants surveyed in this study applied to nearly all participating fellowships. The content of web-based materials varies across program websites, particularly for application requirements, which applicants indicated as the most important electronically available material. Programs should have clear application requirements and provide clinical details on their websites.


Co2+-exchange mechanism of birnessite and its application for the removal of Pb2+ and As(III).
Co-containing birnessites were obtained by ion exchange at different initial concentrations of Co(2+). Ion exchange of Co(2+) had little effect on birnessite crystal structure and micromorphology, but resulted in an increase in specific surface areas from 19.26 to 33.35 m(2)g(-1), and a decrease in both crystallinity and manganese average oxidation state. It was due to that Mn(IV) in the layer structure was reduced to Mn(III) during the oxidation process of Co(2+) to Co(III). The hydroxyl groups on the surface of Co-containing birnessites gradually decreased with an increase of Co/Mn molar ratio owing to the occupance of Co(III) into vacancies and the location of large amounts of Co(2+/3+) and Mn(2+/3+) above/below the vacant sites. This greatly accounted for the monotonous reduction in Pb(2+) adsorption capacity, from 2538 mmol kg(-1) for the unmodified birnessite to 1500 mmol kg(-1) for the Co(2+) ion-exchanged birnessite with a Co/Mn molar ratio of 0.16. The amount of As(III) oxidized by birnessite was enhanced after ion exchange, but the apparent initial reaction rate was greatly decreased. The present work demonstrates that Co(2+) ion exchange has great influence on the adsorption and oxidation behavior of inorganic toxic metal ions by birnessite in water environments.


Linear DNA replication: inverted terminal repeats of five closely related Escherichia coli bacteriophages.
The closely related lipid-containing bacteriophages PRD1, PR4, PR5, PR722 and L17 isolated from different parts of the world have double-stranded DNA genomes which replicate in a linear form. The nucleotide (nt) sequences of the genome termini of these viruses reveal 110-111-bp-long inverted terminal repeats (ITRs). Both ends of the viral DNA are identical. The first 18 bp and the last 35 bp of the ITRs are totally conserved in all viruses. Between these conserved nt sequences there is a variable sequence, which enables us to divide the phages into two groups. Comparison of the virus ITRs led also to the identification of a 10-bp-long A + T stretch, where the only changes observed were transversions between A and T. The termini of the PRD1 virus family genomes exhibit sequence similarities to those of phi 29 and Cp-1 families.


Application of liquid biopsy in bone and soft tissue sarcomas: Present and future.
Bone and soft tissue sarcomas account for approximately 1% of adult solid malignancies and 20% of pediatric solid malignancies. Sarcomas are divided into more than 50 subtypes. Each subtype is highly heterogeneous and characterized by significant morphological and phenotypic variability. Currently, sarcoma characterization is based on tissue biopsies. However, primary and invasive tissue biopsies may not accurately reflect the current disease condition following treatment as is may cause marked changes to the tumor cells. Liquid biopsy offers an alternative minimally invasive approach to provide dynamic tumor information, allowing for the application of precision medicine in the treatment of sarcomas. Recently, there have been numerous blood-based tumor components identified by liquid biopsy in sarcomas, including circulating tumor cells, circulating cell-free nucleic acids, tumor-derived exosomes and metabolites in circulation. Here, we summarize the current evolving technologies and then elaborate on emerging novel concepts that may further propel the field of liquid biopsy in sarcomas. We address the applications in the context of our current knowledge about liquid biopsy in sarcomas and highlight the potential of translating these recent advances into the clinic for more effective management strategies for sarcoma patients.


Assessment of human thermal perception in the hot-humid climate of Dar es Salaam, Tanzania.
Dar es Salaam, Tanzania, is a typical African city along the Indian Ocean coast, and therefore an important urban area to examine human thermal perception in the hot-humid tropical climate. Earlier research on human bioclimate at Dar es Salaam indicated that heat stress prevails during the hot season from October to March, peaking between December and February, particularly the early afternoons. In order to assess the human thermal perception and adaptation, two popular places, one at an urban park and another at a beach environment, were selected and questionnaire surveys were conducted in August-September 2013 and January 2014, concurrently with local micro-meteorological measurements at survey locations. The thermal conditions were quantified in terms of the thermal index of the physiologically equivalent temperature (PET) using the micro-scale climate model RayMan. The thermal comfort range of human thermal comfort and the local thermal adaptive capacity were determined in respect to the thermal index by binning thermal sensation votes. The thermal comfort range was found to be well above that in temperate climates at about 23-31 °C of PET. The study could significantly contribute to urban planning in Dar es Salaam and other coastal cities in the tropics.


Increased circulating big endothelin-1, endothelin-1 and atrial natriuretic peptide in infants and children with heart failure secondary to congenital heart disease.
In order to characterize the changes of five neurohormones in pediatric patients with varying degrees of congestive heart failure (CHF) secondary to congenital heart disease (CHD), we measured plasma neurohormone levels by using radioimmunoassay or high-performance liquid chromatography in 81 subjects including 13 normal children and 68 pediatric patients with CHD. Patients with CHF (n=27) had elevated levels of big endothelin-1 (big ET-1) (29.5+/-1.6 vs. 18.1+/-2.1 pg/ml, p<0.001), endothelin-1 (ET-1) (17.9+/-1.7 vs. 7.8+/-1.7 pg/ml, p<0.001) and norepinephrine (505.6+/-65.6 vs. 219.6+/-23.3 pg/ml, p<0.01) as compared with healthy control subjects (n=13). Plasma norepinephrine levels (505.6+/-65.6 vs. 230.0+/-8.0 pg/ml, p<0.001) and atrial natriuretic peptide (35.5+/-4.2 vs. 7.6+/-0.6 pg/ml, p<0.001) in the 27 patients with CHF were significantly higher than in the 41 patients without CHF. There was also a highly significant stepwise increase in big ET-1, atrial natriuretic peptide and norepinephrine according to the severity of heart failure. Our results suggest that increased circulating neurohormonal activity in CHD relates to the presence and clinical severity of heart failure in children. Plasma levels of big ET-1 and ET-1 were not only significant markers of CHF but also correlated well with the severity of CHF in CHD with left-to-right shunt.


Gastric pressure response to low dose dopamine infusion in normal man.
The gastric pressure response to distension was measured during intravenous infusion of dopamine at a rate of 2 mug min(-1)kg(-1) over 2h 50min in 5 normal volunteers to determine whether dopamine at this dose potentiated gastric adaptive relaxation, leading to a fall in gastric pressure and thus a potential delay in gastric emptying. This would be of obvious importance in patients being given dopamine at this dose to support renal function and at the same time being fed by nasogastric tube. The pressure response decreased during the first hour in all five subjects (p < 0.01). In 2 it recovered during the third hour to pre-infusion values, but in 2 it remained diminished; in 1 subject the results were equivocal. Circulating dopamine, noradrenaline and adrenaline concentrations all increased during dopamine (p < 0.05), but compared with control there was no difference in plasma free fatty acids, glycerol, cortisol or glucose concentrations. Dopamine at 2 mug min(-1) kg(-1) produced a transient fall in gastric pressure in all subjects, and a persistent fall in some. The changes in gastric pressures were seen at infusion rates that produced no metabolic or inotropic effects.


Drug release testing of long-acting intrauterine systems.
Performance evaluation of polydimethylsiloxane (PDMS) based long-acting (e.g. 3-5 years) levonorgestrel (LNG) intrauterine systems (IUSs), such as Mirena®, is challenging due to their complex formulation, locally-acting feature, and extremely long duration of drug release. To achieve such long-term release, a large amount of drug (up to 52 mg in Mirena®) must be incorporated as a drug reservoir in the IUS. Consequently, dose dumping or unanticipated changes in the LNG-IUS in vivo release characteristics may give rise to adverse product safety and efficacy. Therefore, it is crucial to understand, and have appropriate control over, the physicochemical properties and in vitro release characteristics of these products. This requires an understanding of the LNG-IUSs drug release mechanism and the development of a sensitive yet robust in vitro release testing method. There have been no previous reports on in vitro drug release and the release mechanism from LNG-IUSs. This is probably a consequence of the extremely slow drug release rate of LNG-IUSs under real-time in-use conditions (e.g., 3-5 years) and therefore it is impractical to obtain complete release profiles (e.g. there is only 60% release in 5 years for Mirena®). Therefore, the development of appropriate accelerated in vitro release methods is imperative. Following preparation of LNG-IUSs, similar to Mirena®, real-time release was tested in (0.9% w/v NaCl) media in a water shaker bath at 37 °C for over 2 years. Addition of surfactant (sodium dodecyl sulfate (SDS)), elevation of temperature, addition of organic solvents (ethanol (EtOH), isopropanol (IPA), tert-butanol (TBA) and tetrahydrofuran (THF)) and a combination thereof were utilized as release media to accelerate drug release for LNG-IUSs. Complete drug release was achieved in 32 and 672 days in THF and TBA hydro-organic media, respectively. The release profile in THF was considered too fast as it may result in change of release mechanism, whereas the release profile in TBA was deemed suitable following model fitting. Model fitting was performed to understand the release characteristics as well as the release mechanisms. The release rate in the hydro-alcoholic media was linearly proportional to the swelling ratio of the PDMS in the corresponding organic solvents. Zero-order, first-order and two-phase models were utilized to fit the release profiles obtained under the different release conditions. The data analysis was comparable using the parameters from different models given the high R2 values. However, the two-phase model was better in terms of the release mechanism of the LNG-IUSs considering the full drug release profile. The present study will facilitate the process of granting of biowaivers through an in vitro approach, thus reducing the necessity for clinical studies. In addition, it will help reduce the regulatory burden without sacrificing product quality of LNG-IUS products.


Mucosal and systemic immune responses by intranasal immunization using archaeal lipid-adjuvanted vaccines.
The utility of archaeal polar lipids as an adjuvant/delivery system for elicitation of antigen-specific mucosal immune responses in intranasally administered vaccines was investigated. Although unilamellar archaeosomes (liposomes made from archaeal polar lipids) with encapsulated ovalbumin (OVA/archaeosomes) induced anti-OVA IgG antibody responses in sera, they failed to induce anti-OVA IgA antibody responses at mucosal sites. However, the addition of CaCl2 to convert OVA/archaeosomes into an archaeal lipid mucosal vaccine adjuvant and delivery (AMVAD) vaccine (OVA/AMVAD) consisting of larger, particulate, aggregated structures resulted in an efficacious intranasal (i.n.) vaccine. Intranasal immunization of mice with OVA/AMVAD vaccines prepared from various archaeal polar lipid compositions elicited anti-OVA IgA antibody responses in sera, feces, bile, vaginal and nasal wash samples. The i.n. immunization also induced anti-OVA IgG, IgG1 and IgG2a antibody responses in sera, as well as cytotoxic T lymphocyte responses. The mucosal and systemic immune responses induced by OVA/AMVAD immunization were generally sustained over several months, and were subject to memory boost responses. Thus, polar archaeal lipids appear to be promising for developing a non-replicating mucosal adjuvant and vaccine delivery system.


Mind the Gap: HIV Prevention Among Young Black Men Who Have Sex with Men.
Young Black men who have sex with men (YBMSM) suffer profound health inequities in new HIV diagnoses and clinical outcomes. While the evolution of HIV prevention options has become increasingly biomedical, inequities in access and uptake of these modalities persist. Studies suggest that while YBMSM display interest and acceptability of varied HIV prevention options, uptake lags due to the lingering effects of intersectional oppression from racism and sexual prejudice, HIV stigma, institutional and provider bias, and unresolved health policy barriers. Promising avenues to address these barriers have yet to be fully explored. We have the tools to effectively prevent HIV transmission and acquisition among YBMSM, but we have not yet effectively implemented these tools for this priority population. To end the epidemic, we must tailor and adapt HIV prevention strategies to meet the unique intersecting needs, identities, and social contexts of YBMSM.


High-Precision Protein-Tracking With Interferometric Scattering Microscopy.
The mobility of proteins and lipids within the cell, sculpted oftentimes by the organization of the membrane, reveals a great wealth of information on the function and interaction of these molecules as well as the membrane itself. Single particle tracking has proven to be a vital tool to study the mobility of individual molecules and unravel details of their behavior. Interferometric scattering (iSCAT) microscopy is an emerging technique well-suited for visualizing the diffusion of gold nanoparticle-labeled membrane proteins to a spatial and temporal resolution beyond the means of traditional fluorescent labels. We discuss the applicability of interferometric single particle tracking (iSPT) microscopy to investigate the minutia in the motion of a protein through measurements visualizing the mobility of the epidermal growth factor receptor in various biological scenarios on the live cell.


Metabolic function of the CTRP family of hormones.
Maintaining proper energy balance in mammals entails intimate crosstalk between various tissues and organs. These inter-organ communications are mediated, to a great extent, by secreted hormones that circulate in blood. Regulation of the complex metabolic networks by secreted hormones (e.g., insulin, glucagon, leptin, adiponectin, FGF21) constitutes an important mechanism governing the integrated control of whole-body metabolism. Disruption of hormone-mediated metabolic circuits frequently results in dysregulated energy metabolism and pathology. As part of an effort to identify novel metabolic hormones, we recently characterized a highly conserved family of 15 secreted proteins, the C1q/TNF-related proteins (CTRP1-15). While related to adiponectin in sequence and structural organization, each CTRP has its own unique tissue expression profile and non-redundant function in regulating sugar and/or fat metabolism. Here, we summarize the current understanding of the physiological functions of CTRPs, emphasizing their metabolic roles. Future studies using gain-of-function and loss-of-function mouse models will provide greater mechanistic insights into the critical role CTRPs play in regulating systemic energy homeostasis.


New Options in Constipation Management.
Constipation is common in the general population and for those on opioids and/or who are suffering from advanced cancer. Self-management consists of dietary changes, exercise, and laxatives. However, responses to self-management efforts are often inadequate to relieve the subjective and objective experience of constipation. Multiple new anti-constipating medications have recently been tested in randomized trials and the following are available commercially: probiotics, prucalopride, lubiprostone, linaclotide, elobixibat, antidepressants, methylnaltrexone, alvimopan, and naloxegol. This review will discuss the evidence-based benefits of these medications and outline an approach to managing constipation.


Mucosal invasion by fusobacteria is a common feature of acute appendicitis in Germany, Russia, and China.
To investigate the geographic occurrence of mucosa-invading Fusobacteria in acute appendicitis. Carnoy- and formalin-fixated appendices from Germany, Russia, and China were comparatively investigated. Bacteria were detected using fluorescent in situ hybridization. Cecal biopsies from patients with inflammatory bowel disease and other conditions were used as disease controls. Fusobacteria represented mainly by Fusobacterium nucleatum were the major invasive component in bacterial infiltrates in acute appendicitis but were completely absent in controls. The occurrence of invasive Fusobacteria in Germany, Russia, and China was the same. The detection rate in Carnoy-fixated material was 70-71% and in formalin-fixated material was 30-36%. Acute appendicitis is a polymicrobial infectious disease in which F. nucleatum and other Fusobacteria play a key role.


The morphogenesis of elastic fibers.
Elastic fibers have been shown to contain two proteins, insoluble elastin and the elastic fiber microfibril, a glycoprotein. The microfibril has been suggested to play a morphogenetic role in determining the presumptive shape and direction of the forming elastic fiber. The principal alteration seen in individuals with the disease Pseudoxanthoma Elasticum is in insoluble elastin which loses its amorphous appearance and affinity for anionic stains, and takes on a finely granular appearance and shows increased affinity for cationic stains. Normal elastic fiber microfibrils are sometimes associated with this material; although, in general, these structures are not present in the elastic fibers that are markedly altered in this disease.


Incidentally Detected Focal Liver Lesions - A Common Clinical Management Dilemma Revisited.
Detection of asymptomatic focal liver lesions (FLL) is increasing because of a widespread use of modern radiologic imaging. Most of these lesions are benign, though malignancy often has to be ruled out, which is posing a diagnostic challenge. To critically evaluate our treatment strategy in the context of recently published American College of Gastroenterology (ACG) guidelines. The medical records of patients who underwent surgery for asymptomatic, incidentally detected FLL from 2005-2012 were reviewed. Primary end-points were the congruence of suspected diagnosis and final pathology, as well as the identification of predictors of malignancy. A systematic review was undertaken to help define a standardized management. Eighty patients, 37 male and 43 female with a mean age of 57 years (range=16-83) were included, harboring 39 (49%) malignant and 41 (51%) benign, asymptomatic hepatic lesions. Hepatocellular carcinoma (HCC) (n=24) represented most of malignant FLL, followed by cholangiocellular carcinoma (CCC) (n=10), whereas focal nodular hyperplasia (FNH) (n=19) and liver hemangioma (n=7) were the predominant benign entities. Fifty-one patients (64%) had a correct preoperative diagnosis, while patients with FNH were most commonly misdiagnosed (53%). We identified age (p<0.001) and male sex (p=0.013) as risk factors for malignancy in an asymptomatic FLL. Despite recent technical advances of the modern radiology setting a correct preoperative diagnosis in an asymptomatic FLL remains challenging. Male gender and old age seem to correlate with malignancy. In the absence of biomarkers and evidence-based guidelines, a multidisciplinary approach in an experienced tertiary referral center is recommended for an optimized individual management.


Encapsulation of biomolecules for bioanalytical purposes: preparation of diclofenac antibody-doped nanometer-sized silica particles by reverse micelle and sol-gel processing.
In recent years, the sol-gel technique has attracted increasing interest as a unique approach to immobilize biomolecules for bioanalytical applications as well as biochemical and biophysical studies. For this purpose, crushed biomolecule-doped sol-gel glass monoliths have been widely used. In the present work, for the first time, the encapsulation of anti-diclofenac antibodies in silica nanoparticles was carried out by a combination of reverse micelle and sol-gel technique. Cyclohexane was used for the preparation of the microemulsion as organic solvent, while surfactant Igepal CO-520 was found to be the optimal stabilizer. The antibody source was a purified IgG fraction originating from a polyclonal rabbit antiserum. Tetramethyl orthosilicate (TMOS) was used as precursor. Rather uniform, monodispersed and spherical silica particles of about 70nm diameter size were fabricated, as was demonstrated by transmission electron microscopy (TEM) and scanning electron microscopy/energy dispersive X-ray fluorescence analysis (SEM/EDX). The biological activity of the encapsulated antibodies was evaluated by incubation of the nanoparticles with a diclofenac standard solution and analysis of the filtrate and followed washing solutions by a highly sensitive enzyme-linked immunosorbent assay (ELISA), using non-doped particles as blanks. While only about 6% of the added diclofenac was nonspecifically retained by the blank, the corresponding amount of about 66% was much higher with the antibody-doped particles. An obvious advantage of this approach is the general applicability of the developed technique for a mild immobilization of different antibody species.


Coordination polymer-forming liquid Cu(2-isopropylimidazolate).
The structure of the melt state of one-dimensional (1D) coordination polymer crystal Cu(isopropylimidazolate) (melting temperature T m = 143 °C) was characterized by DSC, variable temperature PXRD, solid-state NMR (SSNMR), viscoelastic measurements, XAS, and DFT-AIMD calculations. These analyses suggested "coordination polymer-forming liquid" formation with preserved coordination bonds above T m. Variable chain configurations and moderate cohesive interaction in adjacent chains are the keys to the rarely observed polymer-forming liquid. The melt structure is reminiscent of the common 1D organic polymer melts such as entanglement or random coil structures.


Transplantation of neurospheres after granule cell lesions in rats: cognitive improvements despite no long-term immunodetection of grafted cells.
EGF-responsive C17 murine-derived neural stem cells (neurospheres) were grafted into the dentate gyrus of adult male rats after dentate granule cells lesions produced by colchicine injections. Behavioural performance was evaluated over two post-grafting periods, using tests sensitive to hippocampal dysfunctions. The first period began 1 month after grafting and testing conducted in the water maze and the radial maze distinguished working- and reference-memory performance. The second period began 9 months after grafting and learning performance was also evaluated in a Hebb-Williams maze, in addition to both other tests. The lesions induced lasting deficits in all tests. During the first period, the grafts had no effect in either test. Conversely, during the second period, grafted rats showed a weak improvement in the water maze and a significant increase of reference memory performance in the radial maze. In the Hebb-Williams maze, performance of grafted rats was close to normal. Strengthening the idea that dentate gyrus granule cells play an important role in the acquisition of new (perhaps more configural than only spatial) information, our results, moreover, suggest that neurosphere grafts may foster recovery after damage to point-to-point connection systems in the adult brain.


Dermatologic uses of methotrexate in children: indications and guidelines.
Although methotrexate is frequently employed as an antimetabolic chemotherapeutic agent for childhood cancer, it is rarely used for dermatologic disorders in children. In the pediatric patient whose skin disease is recalcitrant to more conservative treatment, a trial of methotrexate is often appropriate. There are few reports of the drug's use for skin disorders in childhood upon which to base rational therapeutic management, however. In setting guidelines for use in children, we must consider pharmacokinetic studies and methotrexate toxicity observed in managing pediatric cancer.


Acid hydrolases in the suckling rat small intestine. II. On the importance of alkaline phosphatase inhibition in the histochemical localization of acid phosphatase activity.
Phosphatase activities against beta-glycerophosphate, I-naphthyl phosphate and naphthol AS-TR phosphate were investigated, at acid and aldaline pH levels, using unfixed and fixed cryostat sections of suckling rat jejunum. The use of 10 mm EDTA and 10 mm NaF as inhibitors indicated that alkaline phosphate is predominantly located in the microvillous region of the adsorptive cells, while acid phosphatase is located in small particles distributed between the brush borders and the nuclei of these cells. Alkaline phosphatase activity was found to interfere with the localization of acid phosphatase unless EDTA was included in the incubation medium. A modified Gomori medium, containing 10 mm EDTA and additional lead nitrate, is described. Latency experiemtns using this medium, with unfixed sections, indicated the lysosomal nature of particulate acid phosphatase. The discussion stresses the importance of including an aldaline phosphatase inhibitor in incubation media designed to localize extralysosomal acid phosphatase activity.