The hidden curve behind COVID-19 outbreak: the impact of delay in treatment initiation in cancer patients and how to mitigate the additional risk of dying-the head and neck cancer model.

PURPOSE: The rapid spread of the SARS-CoV-2 pandemic around the world caused most healthcare services to turn substantial attention to treatment of these patients and also to alter the structure of healthcare systems to address an infectious disease. As a result, many cancer patients had their treatment deferred during the pandemic, increasing the time-to-treatment initiation, the number of untreated patients (which will alter the dynamics of healthcare delivery in the post-pandemic era) and increasing their risk of death. Hence, we analyzed the impact on global cancer mortality considering the decline in oncology care during the COVID-19 outbreak using head and neck cancer, a known time-dependent disease, as a model. METHODS: An online practical tool capable of predicting the risk of cancer patients dying due to the COVID-19 outbreak and also useful for mitigation strategies after the peak of the pandemic has been developed, based on a mathematical model. The scenarios were estimated by information of 15 oncological services worldwide, given a perspective from the five continents and also some simulations were conducted at world demographic data. RESULTS: The model demonstrates that the more that cancer care was maintained during the outbreak and also the more it is increased during the mitigation period, the shorter will be the recovery, lessening the additional risk of dying due to time-to-treatment initiation. CONCLUSIONS: This impact of COVID-19 pandemic on cancer patients is inevitable, but it is possible to minimize it with an effort measured by the proposed model.

Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes-7.

Breakthroughs in Medicinal Chemistry [...].

Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes-5.

Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes is a series of Editorials which is published on a biannual basis by the Editorial Board of the Medicinal Chemistry section of the journal Molecules [...].

Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes-6.

Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes is a series of Editorials that is published on a biannual basis by the Editorial Board of the Medicinal Chemistry section of the journal Molecules [...].

Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes⁻4.

Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes is a series of Editorials, which is published on a biannual basis by the Editorial Board of the Medicinal Chemistry section of the journal Molecules. [...].

Antimicrobial Peptides in the Battle against Orthopedic Implant-Related Infections: A Review.

Prevention of orthopedic implant-related infections is a major medical challenge, particularly due to the involvement of biofilm-encased and multidrug-resistant bacteria. Current therapies, based on antibiotic administration, have proven to be insufficient, and infection prevalence may rise due to the dissemination of antibiotic resistance. Antimicrobial peptides (AMPs) have attracted attention as promising substitutes of conventional antibiotics, owing to their broad-spectrum of activity, high efficacy at very low concentrations, and, importantly, low propensity for inducing resistance. The aim of this review is to offer an updated perspective of the development of AMPs-based preventive strategies for orthopedic and dental implant-related infections. In this regard, two major research strategies are herein addressed, namely (i) AMP-releasing systems from titanium-modified surfaces and from bone cements or beads; and (ii) AMP immobilization strategies used to graft AMPs onto titanium or other model surfaces with potential translation as coatings. In overview, releasing strategies have evolved to guarantee higher loadings, prolonged and targeted delivery periods upon infection. In addition, avant-garde self-assembling strategies or polymer brushes allowed higher immobilized peptide surface densities, overcoming bioavailability issues. Future research efforts should focus on the regulatory demands for pre-clinical and clinical validation towards clinical translation.

Development and Evaluation of Superabsorbent Hydrogels Based on Natural Polymers.

Superabsorbent hydrogels (SAHs) are three dimensional networks formed by polymers that can absorb aqueous solution of over 100% of their initial weight. This work aimed to develop and characterize SAHs of Chitosan/Xanthan gum (CG), Chitosan/Alginate (CA) and controlled Chitosan (C), Xanthan gum (G), and Alginate (A) produced using "onion-like" methodology. The swelling performance, the morphological structure, the crystallinity, and the Fourier transformed infrared spectroscopy characteristics of SAH were used for the characterization of polyelectrolytes complex. Swelling analysis showed that chitosan has a strong influence on the maintenance of hydrogels structure after swelling, mainly in the acid environment (pH = 2). The chitosan hydrogel presented around 3000% of acidic fluid absorption after 24 h. The chitosan:xanthan gum (1:1 and 2:1 named as C1G1 and C2G1, respectively) hydrogels were the best combination regarding swelling performance in an acid environment, reaching 1665% and 2024%, respectively, as well at pH 7.0, presenting 1005% (C1G1) and 667% (C2G1). Scanning electron microscopy analysis showed samples with pores, and with different shapes. The X-ray diffraction showed the presence of a characteristic peak at 2θ = 20° in all developed composition because of the crystalline nature of chitosan. This work shows the possibility of developing eco-friendly biopolymer-based SAHs at a low cost with a good swelling capacity and stability.

Clinical and biochemical studies in mucopolysaccharidosis type II carriers.

The aim of the study was to characterize clinically and biochemically mucopolysaccharidosis type II (MPS II) heterozygotes. Fifty-two women at risk to be a carrier, with a mean age of 34.1 years (range 16-57 years), were evaluated through pedigree analysis, medical history, physical examination, measurement of iduronate sulfatase (IDS) activities in plasma and in leukocytes, quantification of glycosaminoglycans (GAGs) in urine, and analysis of the IDS gene. Eligibility criteria for the study also included being 16 years of age or older and being enrolled in a genetic counselling programme. The pedigree and DNA analyses allowed the identification of 40/52 carriers and 12/52 non-carriers. All women evaluated were clinically healthy, and their levels of urinary GAGs were within normal limits. Median plasma and leukocyte IDS activities found among carriers were significantly lower than the values found for non-carriers; there was, however, an overlap between carriers' and non-carriers' values. Our data suggests that MPS II carriers show lower plasma and leukocyte IDS activities but that this reduction is generally associated neither with changes in levels of urinary GAGs nor with the occurrence of clinical manifestations.

Report of initial experience in small bowel transplantation at São José do Rio Preto Medical School Hospital.

Intestinal failure is the patient's inability to maintain hydroelectric and nutritional support by the digestive route, arising from massive enterectomy or diseases in which the bowel is incapable of adequately absorbing fluids and nutrients. Patients with intestinal failure associated with short bowel syndrome (SBS) and with other functional diseases with malabsorption or with total parenteral nutrition-related complications (recurrent sepsis and thrombosis of one or more deep venous accesses) are candidates for small bowel transplantation (SBT), which can be an isolated small bowel, a combined liver and small bowel, or a multivisceral graft. At our institution, three isolated SBTs were performed as our initial experience with this transplant.

[Effects of growth hormone on anthropometric and metabolic parameters in android obesity]. / Efeito do hormônio de crescimento sobre parâmetros antropométricos e metabólicos na obesidade andróide.

The aim of the study was to evaluate the effect of GH on body weight, body composition and cardiovascular risk factors in android obese men. Forty non-diabetic subjects aged 20 to 50 years-old with android obesity (WHR > 1) were divided in two groups, on a prospective randomized double-blind basis to receive treatment with GH (0.050 U/kg/day) or placebo for three months. Bioimpedance analysis, DEXA, indirect calorimetry and cardiovascular risk factors were done at the beginning and at the end of the study. Anthropometric measurements were evaluated monthly. Body weight was reduced (3.5 +/- 2.9 kg), as well as BMI (1.2 +/- 1.0 kg/m2), WHR (0.04 +/- 0.01) and fat mass (2.4 +/- 1.0 kg), total cholesterol (4.0 +/- 3.3 mg/dL) and LDL-cholesterol (5.7 +/- 2.7 mg/dL) in GH-treated patients. Percentual changes were statistically different from placebo. Benefits and risks of long-term GH use in obese patients are still largely unknown.

Hypoglycemic activity of polysaccharide fractions containing beta-glucans from extracts of Rhynchelytrum repens (Willd.) C.E. Hubb., Poaceae.

Beta-glucans are soluble fibers with physiological functions, such as interference with absorption of sugars and reduction of serum lipid levels. The objective of the present study was to analyze the distribution of beta-glucans in different tissues of the African grass species Rhynchelytrum repens and also to evaluate their hypoglycemic activity. Leaf blades, sheaths, stems, and young leaves of R. repens were submitted to extraction with 4 M KOH. Analysis of the fractions revealed the presence of arabinose, glucose, xylose, and traces of rhamnose and galactose. The presence of beta-glucan in these fractions was confirmed by hydrolyzing the polymers with endo-beta-glucanase from Bacillus subtilis, followed by HPLC analysis of the characteristic oligosaccharides produced. The 4 M KOH fractions from different tissues were subjected to gel permeation chromatography on Sepharose 4B, with separation of polysaccharides with different degrees of polymerization, the highest molecular mass (above 2000 kDa) being found in young leaves. The molecular mass of the leaf blade polymers was similar (250 kDa) to that of maize coleoptile beta-glucan used for comparison. The 4 M KOH fraction injected into rats with streptozotocin-induced diabetes showed hypoglycemic activity, reducing blood sugar to normal levels for approximately 24 h. This performance was better than that obtained with pure beta-glucan from barley, which decreased blood sugar levels for about 4 h. These results suggest that the activity of beta-glucans from R. repens is responsible for the use of this plant extract as a hypoglycemic drug in folk medicine.

Dhvar5 antimicrobial peptide (AMP) chemoselective covalent immobilization results on higher antiadherence effect than simple physical adsorption.

Bacterial colonization and subsequent biofilm formation is still one of the major problems associated with medical devices. Antimicrobial peptides (AMP) immobilization onto biomaterials surface is a promising strategy to avoid bacterial colonization. However, a correct peptide orientation and exposure from the surface is essential to maintain AMP antimicrobial activity. This work aims to evaluate the effect of the immobilization on antibacterial activity of Dhvar5 (LLLFLLKKRKKRKY), an AMP with a head-to-tail amphipathicity. Dhvar5 was linked to thin chitosan coatings in i) a controlled orientation and exposure, testing covalent immobilization of its N- or C-terminus and using spacers with different lengths and flexibilities or in ii) a random orientation by physical adsorption. Chitosan coating was chosen due to its antimicrobial properties and readiness to be functionalized. Surface characterization demonstrated the chemoselective immobilization of the peptide with different spacers in a similar concentration (∼2 ng/cm2). Efficacy assays demonstrated that covalent immobilization of Dhvar5 exposing its cationic end, improves the chitosan coating antimicrobial effect by decreasing Methicillin-resistant Staphylococcus aureus (MRSA) colonization. This effect was enhanced when longer spacers were used independently of their flexibility. In opposite, immobilized Dhvar5 exposing its hydrophobic end has no effect on bacterial adhesion to chitosan, and when adsorbed in a random orientation even induces bacterial adhesion to chitosan coating.

Anti-inflammatory and antispasmodic activity of Ipomoea imperati (Vahl) Griseb (Convolvulaceae).

Ipomoea imperati (Convolvulaceae) lives on the sandy shores of the Brazilian coast and in other areas of the world. The anti-inflammatory activity of a methanol-water extract of the leaves of I. imperati was investigated in experimental models of acute and subchronic inflammation. Topical application of the extract (10 mg/ear) inhibited mouse ear edema induced by croton oil (89.0 +/- 1.3% by the lipid fraction with an IC50 of 3.97 mg/ear and 57.0 +/- 1.3% by the aqueous fraction with an IC50 of 3.5 mg/ear) and arachidonic acid (42.0 +/- 2.0% with an IC50 of 4.98 mg/ear and 31.0 +/- 2.0% with an IC50 of 4.72 mg/ear). Phospholipase A2, purified from Apis mellifera bee venom, was also inhibited by the extract (5.0 mg/ml lipid and aqueous fraction) in vitro in a dose-dependent manner (85% by the lipid fraction with an IC50 of 3.22 mg/ml and 25% by the aqueous fraction with an IC50 of 3.43 mg/ml). The methanol-water extract of I. imperati (1000 mg/kg) administered by the oral route also inhibited the formation of cotton pellet-induced granulomas (73.2 +/- 1.2% by the lipid fraction and 56.14 +/- 2.7% by the aqueous fraction) and did not cause gastric mucosal lesions. I. imperati extracts (10 mg/ml) also inhibited in a dose-dependent manner the muscle contractions of guinea pig ileum induced by acetylcholine and histamine (IC50 of 1.60 mg/ml for the lipid fraction and 4.12 mg/ml for the aqueous fraction). These results suggest the use of I. imperati as an anti-inflammatory and antispasmodic agent in traditional medicine.

Effects of irradiance on non-structural carbohydrates, growth, and hypoglycemic activity of Rhynchelytrum repens (Willd.) C.E. Hubb. (Poaceae).

Irradiance is a crucial factor in plant development. Different radiant energy levels cause different responses related to plant growth and the production and distribution of dry matter. Considering the relationship between light availability and metabolism of carbohydrates and derived compounds, the aim of this work was to assess the effects of irradiance on non-structural carbohydrate contents and composition, as well as on the hypoglycemiant activity of Rhynchelytrum repens, a pantropical grass species popularly used for diabetes treatment. Plants of R. repens growing under natural irradiance (NI) showed increased content of total soluble carbohydrate (TSC), higher fluctuations in starch content (SC) and higher number of tillers. The flowering process of these plants was preceded by an increase in sucrose. However, their water content was low when compared to that of plants cultivated under low irradiance (LI). The ratio root/aerial organs and SC showed no significant differences in plants grown under LI, although TSC increased and a lower number of tillers were observed during the experimental period. In both conditions, sucrose was the ubiquitous sugar and seemed to be involved in the flowering process. A reduction in the blood sugar level was observed through the intra-peritoneal (IP) administration of the precipitate of aqueous extracts obtained from plants growing in both conditions of light; the supernatant fraction showed no hypoglycemic effect.

Synergistic effect between bioactive glass foam and a perfusion bioreactor on osteogenic differentiation of human adipose stem cells.

Tissue engineering is a multidisciplinary science that combines a structural scaffold and cells to form a construct able to promote regeneration of injured tissue. Bioactive glass foam produced by sol-gel is an osteoinductive material with a network of interconnected macropores necessary for cell colonization. The use of human adipose-derived stem cell (hASC) presents advantages as the potential for a large number of cells, rapid expansion in vitro and the capability of differentiating into osteoblasts. The use of a bioreactor in three-dimensional cell culture enables greater efficiency for cell nutrition and application of mechanical forces, important modulators of bone physiology. The hASC seeded in a bioactive glass scaffold and cultured in osteogenic Leibovitz L-15 medium in a bioreactor with a flow rate of 0.1 mL min(-1) demonstrated a significant increase in cell proliferation and viability and alkaline phosphatase (ALP) activity peak after 14 days. The immunofluorescence assay revealed an expression of osteopontin, osteocalcin and type I collagen from 7 to 21 days after culture. The cells changed from a spindle shape to a cuboidal morphology characteristic of osteoblasts. The polymerase chain reaction assay confirmed that osteopontin, osteocalcin, and ALP genes were expressed. These results indicate that hASCs differentiated into an osteogenic phenotype when cultured in bioactive glass scaffold, osteogenic Leibovitz L-15 medium and a perfusion bioreactor. Therefore, these results highlight the synergism between a bioactive glass scaffold and the effect of perfusion on cells and indicate the differentiation into an osteogenic phenotype.

Endothelial analysis in patients having corneal intrastromal surgery with Cornealring for correction of Keratoconus.

PURPOSE: Evaluate corneal endothelium by means of specular microscopy exam in patients with Keratoconus, before and after Cornealring® corneal intrastromal ring surgery. METHODS: One hundred and two eyes of 67 patients, aged between 12 and 45, with the average age of 27.31 ± 8.15 years, 30 females and 37 males, were selected to be submitted to the implant of Cornealring® corneal ring segments in pre- and post-surgery (six months after the procedure) in the External Diseases and Cornea Ward of the Instituto Panamericano da Visão. RESULTS: Of the 102 eyes treated, only those that received two rings of equal thickness up to 250 µ showed statistical significance between the initial and final mean number of endothelial cells (P = 0.008), a decrease of 10.1% in the mean coefficient of variation (P = 0.003), and a 9.75% decrease in initial and final hexagonal cell counts. The other eyes receiving rings of other thicknesses showed no statistically significant differences between the mean initial and final SM examinations. CONCLUSION: A longer segment is necessary for the confirmation or not of the alterations found in this study, particularly regarding the thickness of the ring used, because with the new technologies and the improvement in the result of deep lamellar transplantation, the decrease in the cell count might represent a problem in the indication of this procedure following thick corneal ring implants.

Report of a Large Brazilian Family With a Very Attenuated Form of Hunter Syndrome (MPS II).

Hunter syndrome, or Mucopolysaccharidosis type II (MPS II), is a rare X-linked recessive disorder caused by a deficiency of the lysosomal enzyme iduronate-2-sulfatase (IDS). The phenotypic spectrum varies from severe to attenuated clinical forms. We report a large Brazilian family with 16 affected individuals exhibiting a very attenuated form of MPS II. Fourteen female carriers were also identified. Twelve affected male patients, whose ages ranged from 1 to 35 years, were examined. Molecular analysis showed a novel missense mutation (p.A77D) in the IDS gene, confirming the diagnosis. Nine of the family members presented some degree of heart damage, though only the proband became symptomatic and required heart transplantation. One 19-year-old adult and 1-year-old twin boys each had a normal echocardiogram. Short stature was found in two adults while macrocephaly was found in one; the remaining adults had anthropometric measures within normal range. All affected adults had normal cognitive development and were able to perform normal daily activities, except one who had mild learning disability. Two patients died due to natural causes beyond 70 years of age. The female carriers did not present any signs of disease. In this large family with a mild form of MPS II and variable degree of clinical manifestations, it is noteworthy that several affected individuals have remained asymptomatic even at advanced age and even without enzyme replacement therapy.