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Alpha fetoprotein (AFP) is associated with hepatocellular carcinoma (HCC) by stimulating the proliferation, metastasis and drug resistance. The application of AFP fragments to inhibit the malignant behaviours induced by AFP is a new strategy for the treatment of HCC. In an effort to design, screen and discover drugs, we attempted to express different human AFP fragments (AFP

We aimed to assess the prevalence rate (PR) of depression, anxiety, posttraumatic stress disorder (PTSD), insomnia, distress, and fear of cancer progression/recurrence among patients with cancer during the COVID-19 pandemic.Studies that reported the PR of six psychological disorders among cancer patients during the COVID-19 pandemic were searched in PubMed, Embase, PsycINFO, and Web of Science databases, from January 2020 up to 31 January 2022. Meta-analysis results were merged using PR and 95% confidence intervals, and heterogeneity among studies was evaluated using IForty studies with 27,590 participants were included. Pooled results showed that the PR of clinically significant depression, anxiety, PTSD, distress, insomnia, and fear of cancer progression/recurrence among cancer patients were 32.5%, 31.3%, 28.2%, 53.9%, 23.2%, and 67.4%, respectively. Subgroup analysis revealed that patients with head and neck cancer had the highest PR of clinically significant depression (74.6%) and anxiety (92.3%) symptoms. Stratified analysis revealed that patients with higher education levels had higher levels of clinically significant depression (37.2%). A higher level of clinically significant PTSD was observed in employed patients (47.4%) or female with cancer (27.9%).This meta-analysis evaluated the psychological disorders of cancer patients during the COVID-19 outbreak. Therefore, it is necessary to develop psychological interventions to improve the mental health of cancer patients during the pandemic.

Background Melasma is a chronic recalcitrant pigmentary disorder whose treatment frustrates physician and patient alike. Tranexamic acid, a plasmin inhibitor, has demonstrated hypopigmenting properties. Aim To compare safety and efficacy of combination of oral tranexamic acid (TXA) and topical fluocinolone-based combination cream (FbTC) with that of topical FbTC alone in melasma. Method One hundred and eighty patients patients of facial melasma of either sex attending dermatology OPD were screened. Consenting 130 participants were randomized into two blinded groups with 65 patients in each group. Group A patients received oral tranexamic acid 250 mg and oral ranitidine 150 mg twice daily and applied a triple combination cream containing fluocinolone acetonide 0.01%, tretinoin 0.05% and hydroquinone 2% once daily, and Group B was asked to take placebo tablets (calcium lactate and multivitamin) and apply the cream only for 12 weeks. Response was evaluated using modified melasma area severity index (mMASI) and graded mMASI improvement at 4th, 8th and 12th weeks, and at 24th week for recurrence. Data were analysed using SPSS software. Results Results were analysed in 120 patients who completed the study with 61 and 59 patients in group A and B, respectively. Demographic profile was equally distributed in both the groups. In group A, 13.1% patients showed marked improvement (>75%) in mMASI as compared to group B (1.7%) at 4th week. By 12th week, 65.6% patients had marked improvement in group A in contrast to only 27.1% in group B. At 24th week, group A (65.6%) had sustained improvement as compared to group B (11.9%) despite stopping treatment; all of which were statistically significant. Recurrence observed was 18.03% in group A vs. 64.4% in group B at 24th week. Conclusion Oral tranexamic acid is definitely a boon to the armamentarium of melasma management and should be used as an adjuvant to fluocinolone-based triple combination cream for a faster, sustained improvement and to prevent recurrence.

Biopharmaceutical product and process development do not yet take advantage of predictive computational modeling to nearly the degree seen in industries based on smaller molecules. To assess and advance progress in this area, spirited coopetition (mutually beneficial collaboration between competitors) was successfully used to motivate industrial scientists to develop, share, and compare data and methods which would normally have remained confidential. The first "Highland Games" competition was held in conjunction with the October 2018 Recovery of Biological Products Conference in Ashville, NC, with the goal of benchmarking and assessment of the ability to predict development-related properties of six antibodies from their amino acid sequences alone. Predictions included purification-influencing properties such as isoelectric point and protein A elution pH, and biophysical properties such as stability and viscosity at very high concentrations. Essential contributions were made by a large variety of individuals, including companies which consented to provide antibody amino acid sequences and test materials, volunteers who undertook the preparation and experimental characterization of these materials, and prediction teams who attempted to predict antibody properties from sequence alone. Best practices were identified and shared, and areas in which the community excels at making predictions were identified, as well as areas presenting opportunities for considerable improvement. Predictions of isoelectric point and protein A elution pH were especially good with all-prediction average errors of 0.2 and 1.6 pH unit, respectively, while predictions of some other properties were notably less good. This manuscript presents the events, methods, and results of the competition, and can serve as a tutorial and as a reference for in-house benchmarking by others. Organizations vary in their policies concerning disclosure of methods, but most managements were very cooperative with the Highland Games exercise, and considerable insight into common and best practices is available from the contributed methods. The accumulated data set will serve as a benchmarking tool for further development of in silico prediction tools.

Background Though melasma is a common skin condition in India, epidemiological studies are few and geographically confined. The present study was designed to gain insights into factors involved in causation and aggravation of melasma, demographic distribution, clinical presentations, and treatment patterns. Methods A cross-sectional multicentric study was conducted in 10 centers distributed across the four regions of India. Data including demographics, personal and family medical history, triggering and aggravating factors, clinical patterns, and details of past treatment regimens were recorded, and severity was estimated using the modified Melasma Area and Severity Index (MASI) score. Data collected by site dermatologists were collated and analyzed. Results The study evaluated 1,001 patients with melasma from 10 centers. Mean age was 38.02 years. Females dominated (85%). Proportion of males was highest in the east (22.2%) and lowest in the south (10.8%). Majority of patients belonged to intermediate skin phototypes. There was a significant difference (P = 0.000) between duration of sun exposure and duration of cooking fire/occupational heat exposure across the four regions. There was a significant association (P = 0.003, Mann-Whitney U test) and a positive correlation between duration of cooking heat/occupational heat exposure and severity of melasma. Sunscreens were used by only one-fifth of the study population (19.6%) whereas use of steroids and triple combinations was more common (28%). Conclusion One of the largest studies on melasma from the subcontinent, this study describes the epidemiological determinants of melasma. Data suggests that the duration of cooking fire/occupational heat exposure may be linked to severity of melasma. Sunscreen use seems inadequate in Indian patients; use of steroid-containing medications is more common.

Gamma‐hydroxybutyrate acid (GHB) is a recreational drug with a high addictive potential. Severe side effects such as GHB‐induced coma are common and linked to increased emergency room attendances. Task‐based functional‐imaging studies have revealed an association between the regular use of GHB and multiple GHB‐induced comas, and altered neurocognitive function. However the effects of multiple GHB‐induced comas and regular GHB‐use on intrinsic brain connectivity during rest remain unknown. The study population consisted of 23 GHB‐users with ≥4 GHB‐induced comas (GHB‐Coma), 22 GHB‐users who never experienced a GHB‐induced coma (GHB‐NoComa) and 24 polydrug users who never used GHB (No‐GHB). Resting‐state scans were collected to assess resting‐state functional‐connectivity within and between the default mode network (DMN), the bilateral central executive network (CEN) and the salience network (SN). The GHB‐NoComa group showed decreased rsFC of the right CEN with a region in the anterior cingulate cortex (p FWE = 0.048) and decreased rsFC between the right CEN and the DMN (p FWE = 0.048) when compared with the No‐GHB group. These results suggest that regular GHB‐use is associated with decreased rsFC within the right CEN and between the right CEN and the DMN. The presence of multiple GHB‐induced comas is not associated with (additional) alterations in rsFC.

Rationale, aims and objectives Interventions aimed at improving chronic care typically consist of multiple interconnected parts, all of which are essential to the effect of the intervention. Limited attention has been paid to the use of routine clinical and administrative data in the evolution of these complex interventions. The purpose of this study is to examine the feasibility of routinely collected data when evaluating complex interventions and to demonstrate how a theory-based, realist approach to evaluation may increase the feasibility of routine data. Methods We present a case study of evaluating a complex intervention, namely, the chronic care model (CCM), in Finnish primary health care. Issues typically faced when evaluating the effects of a complex intervention on health outcomes and resource use are identified by using routine data in a natural setting, and we apply context-mechanism-outcome (CMO) approach from the realist evaluation paradigm to improve the feasibility of using routine data in evaluating complex interventions. Results From an experimentalist approach that dominates the medical literature, routine data collected from a single centre offered a poor starting point for evaluating complex interventions. However, the CMO approach offered tools for identifying indicators needed to evaluate complex interventions. Conclusions Applying the CMO approach can aid in a typical evaluation setting encountered by primary care managers: one in which the intervention is complex, the primary data source is routinely collected clinical and administrative data from a single centre, and in which randomization of patients into two research arms is too resource consuming to arrange.

Inflammation promotes colorectal carcinogenesis. Tumour growth often generates a hypoxic environment in the inner tumour mass. We here report that, in colon cancer cells, the expression of the pro-inflammatory enzyme cyclooxygenase-2 (COX-2) associates with that of the hypoxia response gene carbonic anhydrase-IX (CA-IX). The COX-2 knockdown, achieved by the stable infection of a COX-2 specific short harpin RNA interference (shCOX-2), down-regulates CA-IX gene expression. In colorectal cancer (CRC) cells, PGE(2), the main COX-2 gene products, promotes CA-IX gene expression by ERK1/2 activation. In normoxic environment, shCOX-2 infected/CA-IX siRNA transfected CRC cells show a reduced level of active metalloproteinase-2 (MMP-2) that associates with a decreased extracellular matrix invasion capacity. In presence of hypoxia, COX-2 gene expression and PGE(2) production increase. The knockdown of COX-2/CA-IX blunts the survival capability of CRC cells in hypoxia. At a high cell density, a culture condition that creates a mild pericellular hypoxic environment, the expression of COX-2/CA-IX genes is increased and triggers the invasive potential of colon cancer cells. In human colon cancer tissues, COX-2/CA-IX protein expression levels, assessed by Western blot and immunohistochemistry, correlate each other and increase with tumour stage. In conclusion, these data indicate that COX-2/CA-IX interplay promotes the aggressive behaviour of CRC cells.

Hyperglycemia has been associated with vascular endothelial dysfunction in part by a reduction in nitric oxide (NO) production and increased oxidative stress (e.g., increased superoxide (SO) and hy...

Acute hyperglycemia impairs vascular dilatory function in normal subjects. Normally, vascular endothelial function depends on nitric oxide (NO) production from coupled eNOS in the presence of cofactor 5,6,7,8-tetrahydrobiopterin (BH4). By contrast, 7,8-dihydrobiopterin (BH2, oxidized form of BH4) and/or lack of L-arginine (eNOS substrate) causes eNOS uncoupling to produce superoxide (SO), which can be quickly converted to hydrogen peroxide (H2O2). The role of eNOS coupling status in mediating acute hyperglycemia-induced vascular dysfunction is not known. We simultaneously measured blood NO and H2O2 during the infusion of saline (control), or 20% glucose with or without BH4 (MW=314 g/mol, 6.5 mg/kg), or L-arginine (MW=211 g/mol, 600 mg/kg), or BH2 (MW=239 g/mol, 4 mg/kg) by NO or H2O2 microsensors (100 µm, WPI Inc.) from the femoral veins of male Sprague-Dawley rats. We found that acute hyperglycemia (200 mg/dL, n=6) significantly increased blood H2O2 and reduced blood NO levels compared to the saline grou...

Colon cancer tissues display an increased activity of β-galactoside α2,6 sialyltransferase (ST6Gal.I) and an increased reactivity with the lectin from Sambucus nigra (SNA), specific for α2,6-sialyl-linkages. Experimental and clinical studies indicate a contribution of these alterations to tumor progression, but their molecular bases are largely unknown. In many tissues, ST6Gal.I is transcriptionally regulated through the usage of different promoters that originate mRNAs diverging in the 5`-untranslated regions. RT-PCR analysis of 14 carcinoma samples, all expressing an increased ST6Gal.I enzyme activity, and of the corresponding normal mucosa revealed the presence of at least 2 transcripts. One, containing the 5`-untranslated exons, Y+Z, is thought to represent the “housekeeping” expression, and another previously described in hepatic tissues. Both the Y+Z and the hepatic transcripts were detectable in normal and cancer tissues but that latter form had a marked tendency to accumulate in cancer. The extent of α2,6-sialylation of glycoconjugates, as determined by SNA-dot blot analysis, was markedly enhanced in all cancer specimens, but the level of reactivity only partially correlated with the level of enzyme expression. Western blot analysis revealed a strikingly heterogeneous pattern of SNA reactivity among cancer tissues. These data indicate that: i) during neoplastic transformation of colonic cells, ST6Gal.I expression may be modulated through a differential promoter usage; ii) the extent of α2,6-sialylation of cancer cell membranes is not a direct function of the ST6Gal.I activity, strongly suggesting the existence of other, more complex mechanisms of regulation. Int. J. Cancer 88:58–65, 2000. © 2000 Wiley-Liss, Inc.

Background The authors present their study on oncologic and functional results of supracricoid partial laryngectomies (SPL) performed on 149 patients between January 1984 and December 1995. Methods Cricohyoidopexy (CHP) was carried out on 98 patients and cricohyoidoepiglottopexy (CHEP) on 51 patients. The patients were divided into two groups. The first group included those operated on between January 1984 and December 1992 and who therefore had a minimum follow-up period of 3 years. The second group included those operated on after December 1992 and who therefore had a follow-up period of less than 3 years. The statistical evaluation of this second group was carried out using an actuarial method according to Kaplan-Meier. Results In the first group, survival rate (regarding disease-related deaths) was 94% (95/101), whereas in the second group, survival rate was 95%. There were 9 recurrences in the 149 patients (6.71%), 8 of which occurred after CHP (6 for tumor [T] and 2 for node [N]) and 1 (for T) after CHEP. Three of the 6 recurrences for T after CHP occurred in the hypopharynx, 2 in the peristomal area, and 1 in the arytenoid area. The only recurrence for T after CHEP occurred in the paraglottic area. Decannulation was carried out in 85.7% of CHP patients (84/98) and in 98% of CHEP patients (50/51). The nasogastric tube was kept in position for an average of 28 days (range, 15–90 days) in the CHP patients and 15 days (range, 9–90 days) in the CHEP patients. Swallowing was excellent; only a small number of patients (n = 21) were forced to assume a particular posture during meals. Phoniatric controls performed on 104 patients also showed adequate speech recovery. Conclusions If the indications are applied scrupulously, CHEP is a valid alternative to partial laryngeal surgery and CHP is a possible alternative to total laryngectomy in the treatment of glottic and supraglottic tumors. © 1998 John Wiley & Sons, Inc. Head Neck20: 504–509, 1998.

Subtotal laryngectomy with cricohyoidopexy (CHP) results in a satisfactory cure rate in selected T1b, T2, and T3 supraglottic and glottic cancers. The clinical, oncologic, and functional results of this type of surgery have led to an ever-increasing number of patients undergoing this procedure. This study involved 70 patients operated on from 1984 to 1993 using this surgical procedure. This report also discusses the clinical (cTNM) and pathologic (pTNM) classifications of CHP cases. Fifty-two of these patients were evaluated after a follow-up of more than 3 years. Lymph node treatment protocol comprised 51 functional ipsilateral neck dissections (FNDs), 9 bilateral FNDs, 1 radical ipsilateral dissection, and 1 radical ipsilateral and contralateral FND. There were 6 recurrences (5 local, 1 neck); after CHP physiologic deglutition was recovered in most of the patients (95.5%), and all but 6 (92%) were decannulated. Results were excellent after phoniatric rehabilitation. This surgical procedure may be indicated for selected laryngeal cancers and allows for the preservation of laryngeal functions even when the neoplastic lesions are advanced. However, care must be taken when evaluating the infiltration of the paraglottic space, as that infiltration represents the main cause of failure in this type of surgery.

BACKGROUND Cell blocks can be prepared from residual thin-layer cervicovaginal (ThinPrep) material and can be used in immunohistochemical staining assays for p16INK4a and Ki-67, which are surrogate markers related to human papillomavirus infection and cell proliferation, respectively. The objectives of the current study were 1) to investigate the feasibility and the role of cell block preparations in identifying significant neoplastic and preneoplastic lesions of the uterine cervix and 2) to assess the feasibility of using p16INK4a and Ki-67 immunohistochemical staining patterns on cell blocks to identify significant preneoplastic cervical lesions. METHODS Cervicovaginal cytology specimens from 85 patients were analyzed. Cytologic diagnoses based on ThinPrep Papanicolaou test results were as follows: squamous cell carcinoma was diagnosed in 3 specimens, high-grade squamous intraepithelial lesions (HSIL) were diagnosed in 27 specimens, low-grade squamous intraepithelial lesions (LSIL) were diagnosed in 20 specimens, and atypical squamous cells of uncertain significance (ASCUS) were diagnosed in 11 specimens. Diagnoses of negativity for intraepithelial lesions or malignancy (NILM) were made in 24 specimens. Cell block sections were stained with hematoxylin and eosin and were immunostained with antibodies against p16INK4a protein and Ki-67 antigen. RESULTS The cytomorphologic diagnoses made using cell block preparations were as follows: SCC in 2 specimens, HSIL in 20 specimens, LSIL in 30 specimens, NILM in 32 specimens, and no diagnosis in 1 specimen. In 62 cases (73%), the diagnoses made using cell block preparations were in agreement with the ThinPrep diagnoses. Immunostaining of cell blocks for p16INK4a and Ki-67 exhibited a statistically significant association (P < 0.05) with the presence of significant lesions on either cell block or ThinPrep analysis. CONCLUSIONS To the authors' knowledge, p16INK4a has not been analyzed previously in ThinPrep cell blocks, and the correlation between Ki-67 expression and cell block diagnoses also has not been reported previously. The current results indicate that cell blocks prepared from residual ThinPrep material represent an additional reliable diagnostic tool in the evaluation of cervical samples. Furthermore, immunohistochemical studies may be helpful in differentiating significant preneoplastic changes from other cervical lesions, such as atrophy. Cancer (Cancer Cytopathol) 2004. © 2004 American Cancer Society.

The XPS and Cr Lα ES valence band spectra of b.c.c. Cr-Al alloys in the region 0 to 25 at% Al are presented. The shape and halfwidth of these spectra change notably at approximately 15 at% Al. The results are discussed on the basis of various simple models for the electronic structure of the alloys. The observed changes in the valence band are consistent with the results of magnetic and resistivity measurements. However, the present understanding of the changes in the electronic structure of the Cr-Al alloys is not complete. The effect of the recently discovered inhomogeneity of the microstructure of these alloys in the upper part of the concentration region upon the electronic structure is, together with the antiferromagnetic order, the probable reason for the observed complicated behaviour of the valence band spectra with composition. Die XPS- und CrL-Valenzbandspektren von k.r.z.-Cr-Al-Legierungen im Konzentrationsbereich 0 bis 25 At% Al werden angegeben. Die Form und die Halbwertsbreite dieser Spektren verandern sich sichtbar bei etwa 15 At% Al. Die Resultate werden mit verschiedenen einfachen Modellen der Elektronenstruktur der Legierungen diskutiert. Die beobachteten Veranderungen des Valenzbands sind in Ubereinstimmung mit Resultaten magnetischer und Widerstandsmessungen. Das gegenwartige Verstandnis der Ursachen dieser Veranderungen der Elektronenstruktur der Cr-Al-Legierungen ist jedoch unvollstandig. Der Einflus der kurzlich entdeckten Inhomogenitat der Mikrostruktur dieser Legierungen bei groseren Konzentrationen auf die Elektronenstruktur ist eine wahrscheinliche Ursache fur den beobachteten komplizierten Zusammenhang ihrer Valenzbandspektren mit der Zusammensetzung.

Donnees sur l'etude, par spectroscopies IR et photoelectronique avec excitation par RX, de l'adsorption du diethyldithiophosphate, a partir de solutions aqueuses, sur de la chalcosine (Cu 2 S)