Synthesis and Antitumor Activity of Brominated-Ormeloxifene (Br-ORM) against Cervical Cancer.

Aberrant regulation of ß-catenin signaling is strongly linked with cancer proliferation, invasion, migration, and metastasis, thus, small molecules that can inhibit this pathway might have great clinical significance. Our molecular modeling studies suggest that ormeloxifene (ORM), a triphenylethylene molecule that docks with ß-catenin, and its brominated analogue (Br-ORM) bind more effectively with relatively less energy (-7.6 kcal/mol) to the active site of ß-catenin as compared to parent ORM. Herein, we report the synthesis and characterization of a Br-ORM by NMR and FTIR, as well as its anticancer activity in cervical cancer models. Br-ORM treatment effectively inhibited tumorigenic features (cell proliferation and colony-forming ability, etc.) and induced apoptotic death, as evident by pronounced PARP cleavage. Furthermore, Br-ORM treatment caused cell cycle arrest at the G1-S phase. Mechanistic investigation revealed that Br-ORM targets the key proteins involved in promoting epithelial-mesenchymal transition (EMT), as demonstrated by upregulation of E-cadherin and repression of N-cadherin, Vimentin, Snail, MMP-2, and MMP-9 expression. Br-ORM also represses the expression and nuclear subcellular localization of ß-catenin. Consequently, Br-ORM treatment effectively inhibited tumor growth in an orthotopic cervical cancer xenograft mouse model along with EMT associated changes as compared to vehicle control-treated mice. Altogether, experimental findings suggest that Br-ORM is a novel, promising ß-catenin inhibitor and therefore can be harnessed as a potent anticancer small molecule for cervical cancer treatment.

Functional neuronal circuits promote disease progression in cancer.

The molecular and functional contributions of intratumoral nerves to disease remain largely unknown. We localized synaptic markers within tumors suggesting that these nerves form functional connections. Consistent with this, electrophysiological analysis shows that malignancies harbor significantly higher electrical activity than benign disease or normal tissues. We also demonstrate pharmacologic silencing of tumoral electrical activity. Tumors implanted in transgenic animals lacking nociceptor neurons show reduced electrical activity. These data suggest that intratumoral nerves remain functional at the tumor bed. Immunohistochemical staining demonstrates the presence of the neuropeptide, Substance P (SP), within the tumor space. We show that tumor cells express the SP receptor, NK1R, and that ligand/receptor engagement promotes cellular proliferation and migration. Our findings identify a mechanism whereby intratumoral nerves promote cancer progression.

Zn[Formula: see text]Ni[Formula: see text]Te semiconductor nanocrystals in transparent glass for optoelectronic device applications.

Doping glass with semiconductors, particularly with nanostructured semiconductors, has attracted attention due to the large optical absorption cross-sections of the latter. Based on this property, Ni[Formula: see text] (5 wt%) doped phosphate glass and Zn[Formula: see text]Ni[Formula: see text]Te (x = 0.5, 1.0, 5.0 and 10.0 wt% of Ni[Formula: see text]) nanocrystals (NCs) doped phosphate glasses (GCs) were prepared by fusion method and subsequent heat treatment. Influence of Ni[Formula: see text] on structural, thermo-optical and third-order nonlinear optical properties have been analysed through various spectroscopic characterizations. The XRD pattern of the glass (G) exhibits the amorphous nature of the host material while GCs exhibit not only amorphous halo but also the presence of quantum dots (QDs) or nanocrystals (NCs) phases. TEM analysis of the studied GCs samples confirm the presence of quantum dots (QDs) and bulk NCs with an average diameter of approximately 4.2 [Formula: see text] 0.3 nm and 13.4 [Formula: see text] 0.2 nm, respectively. Several phosphate groups were observed and reported from Raman and FTIR-ATR spectra. The absorption band positions confirmed that Ni[Formula: see text] ions resemble to the octahedral symmetry. The intensity of absorption band around 1352 nm ([Formula: see text]T[Formula: see text](F) [Formula: see text] [Formula: see text]A[Formula: see text](F)) increased with the increase of Ni[Formula: see text] in GCs which is an indicative of the [Formula: see text]Ni[Formula: see text] coordination. The emission properties such as emission cross-sections ([Formula: see text]) full width at half maxima (FWHM) for the [Formula: see text]T[Formula: see text](D) [Formula: see text] [Formula: see text]T[Formula: see text](F) (visible) and [Formula: see text]A[Formula: see text](F) [Formula: see text] [Formula: see text]T[Formula: see text](F) (near-infrared) emission transitions were reported. Among the glass-containing semiconductor nanocrystals (GCs), the emission cross-sections in GC4 sample (x = 10% of Ni[Formula: see text]) are the largest for both the visible (11.88 [Formula: see text] 10[Formula: see text] cm[Formula: see text]) and infrared (0.98 [Formula: see text] 10[Formula: see text] cm[Formula: see text]) transitions. Thermal diffusivity (D), thermal conductivity (K) and temperature dependent optical path length change (ds/dT) were obtained through time-resolved thermal lens (TL) and thermal relaxation (TR) methods. The D and K parameters do not change significantly with increase of Ni[Formula: see text] ions (0.5-5%) in GCs. Nonlinear-refractive index and nonlinear absorption of the studied samples were also obtained using femtosecond Z-scan technique. The increase of nonlinear absorption coefficient ([Formula: see text]) is observed from GC2 (2.53 [Formula: see text] 10[Formula: see text] cm/W) to GC4 (7.98 [Formula: see text] 10[Formula: see text] cm/W). The GC4, sample with 10 wt% of Ni[Formula: see text], showed the lowest ds/dT (1.22 [Formula: see text] 10[Formula: see text] K[Formula: see text]) with good lasing (FOM and emission cross-sections) and nonlinear absorption properties suggesting that it can be a good candidate for visible-red emission light conversion in LED technology.

Circumscribed Palmar Hypokeratosis With Superimposed Actinic Keratosis.

A man in his late 70s with a history of psoriasis and non-melanoma skin cancer presented with a progressive rash on his right thenar eminence. He first noticed it about one year ago. He denied any pruritus in the affected region but did note some overlying skin breakdown. He had used topical betamethasone and calcipotriene cream in the past with minimal improvement. Physical examination revealed a pink atrophic plaque with linear hyperkeratotic borders and central fissuring on the right thenar eminence extending into the first webspace. A shave biopsy revealed hypokeratosis with a rim of surrounding hyperkeratosis and associated parakeratosis, basal keratinocyte atypia, and lichenoid inflammation. These histopathological features were consistent with circumscribed palmar hypokeratosis and central actinic keratosis. Circumscribed palmar hypokeratosis is often considered a benign entity, but there have been reports suggesting an association with premalignancy. The decision was made to treat with 5-fluorouracil and calcipotriene cream twice daily for six weeks. At his two-month follow-up, he endorsed a robust reaction, which was further suggestive of premalignant change. He had a near-complete resolution of the rash. This case features circumscribed palmar hypokeratosis and suggests a novel treatment option for patients who develop concomitant actinic keratosis.

Doubling down on the future of gynecologic oncology: The SGO future of the profession summit report.

The original vision of the field of gynecologic oncology was to establish a multidisciplinary approach to the management of patients with gynecologic cancers. Fifty years later, scientific advances have markedly changed the overall practice of gynecologic oncology, but the profession continues to struggle to define its value-financial and otherwise. These issues were examined in full at the Society of Gynecologic Oncology (SGO) Future of the Profession Summit and the purpose of this document is to summarize the discussion, share the group's perceived strengths, weaknesses, opportunities, and threats (SWOT) for gynecologic oncologists, further educate members and others within the patient care team about the unique role of gynecologic oncologists, and plan future steps in the short- and long- term to preserve the subspecialty's critical mission of providing comprehensive, longitudinal care for people with gynecologic cancers.

Near-infrared quantum cutting luminescence in Pr3+/Yb3+ doped lead bismuth borate glass.

In this paper, thermally stable lead-bismuth-borate glasses were doped with 0.5 mol% of Pr3+ ions at several concentration levels of Yb3+ ions. Structural characterizations were performed via Raman, differential scanning calorimetry, optical absorption and fluorescence spectra. The Judd-Ofelt intensity parameter, [Formula: see text], of Pr3+ doped glass was comparatively higher than those from reported ones, which reflects the increase of co-valency and asymmetry of chemical bonds in the local environment of Pr3+. Near-infrared emission in 900-2200 nm wavelength range was recorded through 443 nm blue laser pumping. Visible to near-IR quantum cutting and concentration quenching mechanisms were discussed to understand the luminescent behaviour. Intense IR emission ([Formula: see text] features generated by absorbing one visible photon leads to quantum efficiencies close to 128% in Pr3+/Yb3+ co-doped samples which may improve the solar spectrum absorption and accordingly, increase the efficiency of c-Si solar cells. Emission cross-section, lifetime, figure of merit and gain bandwidth corresponding to Pr3+: [Formula: see text] ([Formula: see text]m) were comparatively reported suggesting that the glass with molar composition 0.5Pr3+/0.1Yb3+ might be a potential candidate for [Formula: see text]m laser operation with low pump threshold.

Origin geographical classification of green coffee beans (Coffea a rabica L.) produced in different regions of the Minas Gerais state by FT-MIR and chemometric.

The present work was proposal the potential evaluation of Fourier-Transform Mid-Infrared (FT-MIR) associated with chemometric approach in green beans, in order to discriminate the origin of special Arabica coffees in a single state that has heterogeneous environments. Partial Least Squares Discriminant Analysis (PLS-DA) model presented as result: 3 latent variables, R 2 X (cum) = 0.892, R 2 Y (cum) = 0.659; Q 2 Y (cum) = 0.494, RMSEP = 0.182387, p-value CV-Anova = 0.009, 100% of both sensitivity and specificity and the prediction classification obtained was: 100, 83.33, 100, 83.33% for class 1, class 2, class 3 and class 4, respectively. These results can be considered adequate for the proposed hypothesis. The obtained results that the regions have markers such as trigonelline, chlorogenic and fatty acids, sensitive to absorption in the mid-infrared and that are able to determine the origin of green coffee beans of Arabica. Thus, the FT-MIR associated with chemometrics has the potential to employ speed, modernity and cost reduction in the certification of origin of coffees.

Randomized Controlled Phase II Evaluation of Two Dose Levels of Bupropion Versus Placebo for Sexual Desire in Female Cancer Survivors: NRG-CC004.

PURPOSE: Because of the negative impact of cancer treatment on female sexual function, effective treatments are warranted. The purpose of this multisite study was to evaluate the ability of two dose levels of extended-release bupropion, a dopaminergic agent, to improve sexual desire more than placebo at 9 weeks, measured by the desire subscale of the Female Sexual Function Index (FSFI), and to evaluate associated toxicities. METHODS: Postmenopausal women diagnosed with breast or gynecologic cancer and low baseline FSFI desire scores (< 3.3), who had completed definitive cancer therapy, were eligible. Women were randomly assigned to receive 150 mg or 300 mg once daily of extended-release bupropion or a matching placebo. t-tests were performed on the FSFI desire subscale to evaluate whether there was a significantly greater change from baseline to 9 weeks between placebo and each bupropion arm as the primary end point. Sixty-two patients per arm provided 80% power using a one-sided t-test. RESULTS: Two hundred thirty women were randomly assigned from 72 institutions through the NRG Oncology NCORP network. At 9 weeks, there were no statistically significant differences in change of the desire subscale scores between groups; participants in all three arms reported improvement. The mean changes for each arm were placebo 0.62 (standard deviation [SD] = 1.18), 150-mg once daily bupropion 0.64 (SD = 0.95), and 300-mg once daily bupropion 0.60 (SD = 0.89). Total and subscale scores on the FSFI were low throughout the study, indicating dysfunction in all groups. CONCLUSION: Bupropion was not more effective than placebo in improving the desire subscale of the FSFI. Subscale and total scores of the FSFI demonstrated dysfunction throughout the 9 weeks of the study. More research is needed to support sexual function in female cancer survivors.

Intra-Tumoral Nerve-Tracing in a Novel Syngeneic Model of High-Grade Serous Ovarian Carcinoma.

Dense tumor innervation is associated with enhanced cancer progression and poor prognosis. We observed innervation in breast, prostate, pancreatic, lung, liver, ovarian, and colon cancers. Defining innervation in high-grade serous ovarian carcinoma (HGSOC) was a focus since sensory innervation was observed whereas the normal tissue contains predominantly sympathetic input. The origin, specific nerve type, and the mechanisms promoting innervation and driving nerve-cancer cell communications in ovarian cancer remain largely unknown. The technique of neuro-tracing enhances the study of tumor innervation by offering a means for identification and mapping of nerve sources that may directly and indirectly affect the tumor microenvironment. Here, we establish a murine model of HGSOC and utilize image-guided microinjections of retrograde neuro-tracer to label tumor-infiltrating peripheral neurons, mapping their source and circuitry. We show that regional sensory neurons innervate HGSOC tumors. Interestingly, the axons within the tumor trace back to local dorsal root ganglia as well as jugular-nodose ganglia. Further manipulations of these tumor projecting neurons may define the neuronal contributions in tumor growth, invasion, metastasis, and responses to therapeutics.

Effectiveness of profile by Sanford behavioral weight loss program for weight loss following endometrial cancer treatment.

OBJECTIVE: To examine differences in weight change and Body Mass Index (BMI) at 12 months among women in remission from endometrial cancer who enrolled in a behavioral weight loss (BWL) program and a matched patient control group. METHODS: Women (n = 22) were enrolled into the BWL program and were compared against a control group (n = 28) that accounted for age, BMI, cancer type, cancer stage, and treatment dates. The BWL program included weekly health coaching meetings that targeted nutrition, activity, and behavior change topics. RESULTS: Women enrolled in the BWL program completed 28.3 ± 14.1 appointments over 12 months resulting in an average weight change of -14.2 ± 7.8 kg (-13.3 ± 7.4%) at 6 months and -16.4 ± 12.5 kg (-15.3 ± 11.4%) at 12 months (all p < 0.001). Women in the control group had a weight change of -1.7 ± 8.4 kg (-2.3 ± 7.6%) at 12 months which was significantly different than the BWL condition (p < 0.001). BMI was significantly reduced in the BWL group at 6 months (-4.8 ± 4.5, p < 0.001) and 12 months (-5.2 ± 5.9, p < 0.001) and significantly different than in the control group at 12 months (-0.9 ± 3.2, p = 0.007). CONCLUSIONS: The BWL program yielded clinically significant weight loss for endometrial cancer survivors. Future work should include longer follow up periods and include additional behavioral and psychosocial outcomes.

Características clínico-epidemiológicas en pacientes con síndrome metabólico / Clinical and epidemiological characteristics of patients with metabolic syndrome

Introduction: The metabolic syndrome is defined by the presence of obesity, fundamentally central, hypertension, diabetes mellitus, and dyslipidemia; Objective: To characterize patients with metabolic syndrome from the clinical and epidemiological points of view. Methods: A descriptive and prospective study of 640 patients with metabolic syndrome was carried out, who were admitted to Dr. Juan Bruno Zayas Alfonso Teaching General Hospital from Santiago de Cuba during 2019. Information was statistically processed and analyzed; through the SPSS 11.5.1 program, by using the percentage as summary measure for qualitative variables. Results: In the serie, 26.8% of the patients belonged to the age group 40-49, and 53,0% were of female sex. Likewise, diabetes mellitus and hypertension were the associated diseases in 22,3 y 22,2 % of the patients, respectively, while 67,7 % had a saturated fats diet. Social drinkers were identified in 53,0 % of cases, and the heavy smokers in 47.0 %. Conclusions: Personal and family associated diseases prevailed as associated personal and family diseases, what shows the closed relationship between them and the metabolic syndrome. Health promotion and education should be considered in patients with metabolic syndrome from the primary care, as well as the distribution of medical care for this group of hospital institutions, to prevent and control risk factors related to its emergence.

Introducción: El síndrome metabólico está definido por la presencia de obesidad, fundamentalmente central; hipertensión arterial; diabetes mellitus y dislipidemias. Objetivo: Caracterizar a pacientes con síndrome metabólico desde el punto de vista clínico-epidemiológico. Métodos: Se realizó un estudio descriptivo y prospectivo de 640 pacientes con síndrome metabólico atendidos en el Hospital General Docente Dr. Juan Bruno Zayas Alfonso de Santiago de Cuba durante el año 2019. La información se procesó y analizó estadísticamente mediante el programa SPSS 11.5.1, con el empleo del porcentaje como medida de resumen para variables cualitativas. Resultados: En la serie, 26,8 % perteneció al grupo de edades de 40-49 años y 53,0 % era del sexo femenino. Asimismo, la diabetes mellitus y la hipertensión arterial figuraron como enfermedades asociadas en 22,3 y 22,2 % de los pacientes, respectivamente, en tanto 67,7 % ingería dieta a base de grasa saturada. Los bebedores sociales fueron identificados en 53,0 % de los casos y los fumadores empedernidos en 47,0 %. Conclusiones: La diabetes mellitus y la hipertensión arterial predominaron como enfermedades personales y familiares asociadas, lo que muestra la estrecha relación entre estas y el síndrome metabólico. Deben considerarse la educación y promoción de salud en pacientes con síndrome metabólico desde la atención primaria, así como la verticalización de la atención médica para este grupo en instituciones hospitalarias, a fin de prevenir y controlar los factores de riesgo relacionados con su aparición.

Unprecedented multiphonon vibronic transitions of erbium ions on copper nanoparticle-containing tellurite glasses.

Erbium-doped tellurite glass containing copper nanoparticles showed multi-band emission of one particular transition (4I9/2→4I15/2, at 980 nm) due to electron-lattice coupling. The present study reports the vibronic transitions of intraconfigurational 4fn transitions of Er3+ ions in a tellurite host matrix at room temperature for the first time. The mechanisms of multiphoton transitions and the effect of laser heating are discussed here. This unprecedented behavior enables the design of a plethora of different applications spanning from tunable emission in the near infrared, such as lasers for bioimaging and biomedical fields, to energy conversion by thermophotovoltaic conversion of thermal radiation.

FT-NIR associado a método quimiométrico para discriminar resíduos de antimicrobianos e antiparasitário no leite / FT-NIR coupled to chemometric method to discriminate antimicrobial and antiparasitic residues in milk

Introdução: O leite é um dos alimentos mais consumidos pelos seres humanos. Proteínas, vitaminas, gordura, carboidratos e sais minerais fazem parte de sua composição e desempenham importantes funções para a nutrição humana. A prática de adulteração no leite é antiga e ainda se faz presente nos dias de hoje em diversos países, inclusive no Brasil. A fim de obter lucro maior, alguns fornecedores costumam adicionar ao leite: água, amido, citrato, ureia, soda cáustica, cloreto de sódio, sacarose, soro do leite, melamina e outros componentes. No entanto, ainda há outro problema, o da contaminação do leite por medicamentos veterinários. Estes podem causar danos à saúde do consumidor e prejuízos para a produção de seus derivados. Objetivo: O presente trabalho propõe uma metodologia que permite detectar de maneira rápida a presença de resíduos de medicamentos veterinários em leites, dentro do limite máximo de resíduos de cada droga. Métodos: Fez-se o uso da espectroscopia no infravermelho próximo por transformada de Fourier associada à análise de componentes principais. A espectroscopia no infravermelho tem sido utilizada não somente para a autenticidade de laticínios, mas para determinar sua qualidade. Resultados: Conseguiu-se detectar resíduos de penicilina, oxitetraciclina e enrofloxacino, e também do antiparasitário ivermectina nas amostras de leites. Conclusão: A metodologia detectou de maneira rápida e precisa os resíduos das drogas analisadas, mesmo em concentrações muito baixas. Assim, é uma opção a outras existentes, já utilizadas para tal objetivo. (AU)

Introduction: Milk is one of the most consumed foods by humans. Proteins, vitamins, fat, carbohydrates and minerals are part of its composition and play important roles in human nutrition. The practice of adulteration in milk is old and is still present today in several countries, including Brazil. In order to obtain a higher profit, some suppliers usually add to the milk: water, starch, citrate, urea, caustic soda, sodium chloride, sucrose, whey, melamine and other components. However, there is still another problem, that of contamination of milk by veterinary medicines. These can cause damage to the health of the consumer and damage to the production of its derivatives. Objective: The present work proposes a methodology that allows to quickly detect the presence of residues of veterinary medicines in milk, within the maximum residue limit of each drug. Methods: The use of spectroscopy in the near infrared by Fourier transform associated with the analysis of principal components was used. Infrared spectroscopy has been used not only for the authenticity of dairy products, but to determine their quality. Results: It was possible to detect residues of penicillin, oxytetracycline and enrofloxacin, and also of the antiparasitic ivermectin in the milk samples. Conclusion: The methodology fastly and accurately detected the residues of the analyzed drugs, even in very low concentrations. Thus, it is an option to other existing ones, already used for this purpose. (AU)

Comparative data on effects of alkaline pretreatments and enzymatic hydrolysis on bioemulsifier production from sugarcane straw by Cutaneotrichosporon mucoides.

Bioemulsifiers are surface active compounds which could be potentially used in food processing, cosmetic sector and oil recovery. Sugarcane straw (SS), was used as the raw substrate for the production of bio-emulsifiers (BE) by Cutaneotrichosporon mucoides. Three different delignification strategies using dilute sodium hydroxide, sodium sulfite and ammonium hydroxide followed by enzymatic hydrolysis (Cellic CTec 2, 7.5% total solids, 15 FPU/g, 72 h) were studied. Enzyme hydrolysis of ammonium hydroxide pretreated SS showed a maximum of 62.19 ± 0.74 g/l total reducing sugars with 88.35% hydrolytic efficiency (HE) followed by sodium hydroxide (60.06 ± 0.33 g/l; 85.40% HE) and sodium sulfite pretreated SS (57.22 ± 0.52 g/l; 84.71% HE), respectively. The ultrastructure of SS (native and delignified) by fourier transform-infrared and near infrared spectroscopy, revealed notable structural differences. The fermentation of hydrolysates by C. mucoides into bioemulsifiers showing emulsification index (EI) of 54.33%, 48.66% and 32.66% from sodium sulfite, sodium hydroxide, and ammonium hydroxide pretreated SS, respectively.