University of Puerto Rico at Bayamón

The emergence of antibiotic-resistant bacteria is a major threat to world-wide public health. Functionalized nanoparticles could offer novel strategies in this post-antibiotic era. In this study, we developed nanocomposites of silver nanoparticles decorated with graphene quantum dots (Ag-GQDs) using pulsed laser synthesis. The nanocomposites were PEGylated, which increases their biocompatibility and solubility in aqueous solutions. The HR-TEM micrographs of bare GQDs show that their size is in the range of 1.6–4 nm, and the lattice spacing is 0.214 nm, which corresponds to the (1 0 0) lattice fringes of graphene. The antibacterial activity of Ag-GQDs was evaluated and compared to that of bare GQDs and commercial silver nanoparticles (Ag-NPs) against both Gram-negative and Gram-positive bacteria, using Pseudomonas aeruginosa and Staphylococcus aureus as model bacteria, respectively. Concentration values of 25 and 50 μg/mL are required for Ag-GQDs to inhibit the growth of S. aureus and P. aeruginosa bacteria, respectively. The fractional inhibitory concentration (FIC) index is below 0.5 indicating that there is a synergistic effect between Ag-NPs and GQDs. Kirby–Bauer tests showed that Ag-GQDs inhibit P. aeruginosa and S. aureus, in contrast to bare GQDs and Ag-NPs alone. Cell viability of normal mammalian cells treated with Ag-GQDs showed that cell viability is maintained at 100% for cells incubated with Ag-GQDs. The decoration of Ag-NPs with GQDs minimizes their cytotoxicity in mammalian cells and increases their biocompatibility. Ag-GQDs have potential applications in the fabrication of antibacterial coatings, self-sterile textiles, and personal care products.

Background: Once-daily glecaprevir coformulated with pibrentasvir (glecaprevir/pibrentasvir) demonstrated high rates of sustained virologic response 12 weeks after treatment (SVR12) in patients with hepatitis C virus (HCV) genotype 1-6 infection. This phase 3 study evaluated the efficacy and safety of glecaprevir/pibrentasvir in patients with chronic HCV genotype 1-6 and human immunodeficiency virus type 1 (HIV-1) coinfection, including patients with compensated cirrhosis. Methods: EXPEDITION-2 was a phase 3, multicenter, open-label study evaluating glecaprevir/pibrentasvir (300 mg/120 mg) in HCV genotype 1-6/HIV-1-coinfected adults without and with compensated cirrhosis for 8 and 12 weeks, respectively. Patients were either HCV treatment-naive or experienced with sofosbuvir, ribavirin, or interferon, and antiretroviral therapy (ART) naive or on a stable ART regimen. Treatment-experienced genotype 3-infected patients were excluded. The primary endpoint was the SVR12 rate. Results: In total, 153 patients were enrolled, including 16 (10%) with cirrhosis. The SVR12 rate was 98% (n = 150/153; 95% confidence interval, 95.8-100), with no virologic failures in 137 patients treated for 8 weeks. One genotype 3-infected patient with cirrhosis had on-treatment virologic failure. Most adverse events were mild in severity; 4 patients (2.6%) had serious adverse events, all deemed unrelated to glecaprevir/pibrentasvir. Treatment discontinuation was rare (<1%). All patients treated with ART maintained HIV-1 suppression (<200 copies/mL) during treatment. Conclusions: Glecaprevir/pibrentasvir for 8 weeks in noncirrhotic and 12 weeks in cirrhotic patients is a highly efficacious and well-tolerated treatment for HCV/HIV-1 coinfection, regardless of baseline HCV load or prior treatment with interferon or sofosbuvir. Clinical trial registration: NCT02738138.

Alternative combinations of antiretrovirals (ARVs) are desired to increase treatment options for HIV-infected patients. PROGRESS was a randomized, open-label, 96-week pilot study comparing a regimen of lopinavir/ritonavir (LPV/r) 400/100 mg twice daily in combination with either raltegravir (RAL) 400 mg twice daily or tenofovir/emtricitabine (TDF/FTC) 300/200 mg once daily in ARV-naive adults. A total of 206 subjects were randomized and treated (LPV/r+RAL, N=101; LPV/r+TDF/FTC, N=105). Demographics and baseline characteristics were similar across treatment groups. At 96 weeks, 66.3% of subjects receiving LPV/r+RAL and 68.6% of subjects receiving LPV/r+TDF/FTC were responders (plasma HIV-1 RNA levels<40 copies/ml) by the FDA time to loss of virologic response (FDA-TLOVR) algorithm (p=0.767). Mean CD4(+) T cell increases through 96 weeks were similar between treatment groups (LPV/r+RAL=281 cells/mm(3), LPV/r+TDF/FTC=296 cells/mm(3), p=0.598). Safety and tolerability were generally similar between groups. The LPV/r+RAL regimen resulted in greater increases in peripheral fat, but not trunk fat, compared with LPV/r+TDF/FTC. There was a statistically significantly greater mean reduction in estimated glomerular filtration rate from baseline to week 96 in the LPV/r+TDF/FTC group compared with the LPV/r+RAL group (-7.33 ml/min vs. -1.43 ml/min; p=0.035). The LPV/r+TDF/FTC group had a statistically significant (p<0.001) mean percent decrease from baseline to week 96 in bone mineral density, which was significantly different from the mean percent change in the LPV/r+RAL group (-2.48% vs. +0.68%, p<0.001). These efficacy and safety observations support further evaluation of the LPV/r+RAL regimen.

The medicinal mushroom Ganoderma lucidum (Reishi) was tested as a potential therapeutic for Inflammatory Breast Cancer (IBC) using in vivo and in vitro IBC models. IBC is a lethal and aggressive form of breast cancer that manifests itself without a typical tumor mass. Studies show that IBC tissue biopsies overexpress E-cadherin and the eukaryotic initiation factor 4GI (eIF4GI), two proteins that are partially responsible for the unique pathological properties of this disease. IBC is treated with a multimodal approach that includes non-targeted systemic chemotherapy, surgery, and radiation. Because of its non-toxic and selective anti-cancer activity, medicinal mushroom extracts have received attention for their use in cancer therapy. Our previous studies demonstrate these selective anti-cancer effects of Reishi, where IBC cell viability and invasion, as well as the expression of key IBC molecules, including eIF4G is compromised. Thus, herein we define the mechanistic effects of Reishi focusing on the phosphoinositide-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway, a regulator of cell survival and growth. The present study demonstrates that Reishi treated IBC SUM-149 cells have reduced expression of mTOR downstream effectors at early treatment times, as we observe reduced eIF4G levels coupled with increased levels of eIF4E bound to 4E-BP, with consequential protein synthesis reduction. Severe combined immunodeficient mice injected with IBC cells treated with Reishi for 13 weeks show reduced tumor growth and weight by ∼50%, and Reishi treated tumors showed reduced expression of E-cadherin, mTOR, eIF4G, and p70S6K, and activity of extracellular regulated kinase (ERK1/2). Our results provide evidence that Reishi suppresses protein synthesis and tumor growth by affecting survival and proliferative signaling pathways that act on translation, suggesting that Reishi is a potential natural therapeutic for breast and other cancers.

ABSTRACT Fifteen species of Lepidoptera occurred in large numbers in spring and early summer after the passage of Hurricane Hugo over the north-east of Puerto Rico. Spodoptera eridania (Noctuidae) was the most common of the larvae and fed on 56 plant species belonging to 31 families. All the Lepidoptera fed on early successional vegetation. Some of the plants represent new host plants for these species. The outbreaks appeared to be based on the flush of new foliage that developed in the Luquillo Mountains after the passage of the hurricane. The end of the S. eridania outbreak was concurrent with the consumption of its preferred host plants and to an apparent increment in parasitism by ichneumonids (Hymenoptera). Parasitism by tachinids (Diptera) may have contributed to the reduction in abundance of other Lepidoptera species that were temporarily very abundant. Natural enemies of S. eridania were recorded for the first time in Puerto Rico.

We previously reported that Ganoderma lucidum extract (GLE) demonstrate significant anticancer activity against triple negative inflammatory breast cancer models. Herein, we aimed to elucidate the bioactive compounds of GLE responsible for this anticancer activity. We performed NMR, X-ray crystallography and analogue derivatization as well as anti-cancer activity studies to elucidate and test the compounds. We report the structures of the seven most abundant GLE compounds and their selective efficacy against triple negative (TNBC) and inflammatory breast cancers (IBC) and other human cancer cell types (solid and blood malignancies) to illustrate their potential as anticancer agents. Three of the seven compounds (ergosterol, 5,6-dehydroergosterol and ergosterol peroxide) exhibited significant in vitro anticancer activities, while we report for the first time the structure elucidation of 5,6-dehydroergosterol from Ganoderma lucidum. We also show for the first time in TNBC/IBC cells that ergosterol peroxide (EP) displays anti-proliferative effects through G1 phase cell cycle arrest, apoptosis induction via caspase 3/7 activation, and PARP cleavage. EP decreased migratory and invasive effects of cancer cells while inhibiting the expression of total AKT1, AKT2, BCL-XL, Cyclin D1 and c-Myc in the tested IBC cells. Our investigation also indicates that these compounds induce reactive oxygen species, compromising cell fate. Furthermore, we generated a superior derivative, ergosterol peroxide sulfonamide, with improved potency in IBC cells and ample therapeutic index (TI>10) compared to normal cells. The combined studies indicate that EP from Ganoderma lucidum extract is a promising molecular scaffold for further exploration as an anti-cancer agent.

Acetanilides efficiently undergo Vilsmeier-Haack cyclisation in micellar media to afford 2-chloro-3-formyl quinoline derivatives in good yields. This procedure works efficiently in CTAB (cetyl trimethyl ammonium bromide), SDS (sodium dodecyl sulphate) and TX (Triton-X-100) media under reflux conditions particularly from deactivated acetanilides in good yields.

The purpose of this study was to analyse the beliefs about inclusion and teaching students with disabilities of physical education teachers from various countries and cultures. The participants were 29 physical education teachers from Ghana (Africa), Japan, the US and Puerto Rico. The research method was explanatory multiple‐case study situated in the theory of planned behaviour. The primary data sources were attitude surveys and interviews. Survey data were analysed with descriptive statistics and the interview data were analysed using a constant comparative method. Results indicate that the teachers’ beliefs tended to vary on inclusion and teaching students with disablities. Paradoxically, they expressed compelling intrinsic motives while voicing a multiplicity of concerns on teaching students with disabilities. They all desired greater opportunities for relevant professional development, which should be made available more frequently by school districts.

The incentives for large-scale hydropower development in Sweden are usually explained in terms of the early 20th-century belief in progress and the need for energy to fuel industrialization and modernization. For reindeer husbandry, the consequences and cumulative effects of this large-scale landscape conversion, and the societal changes it entailed are still largely a story to be told as impacts and effects constantly evolve in the socio-ecological system of the reindeer grazing lands. The present article 1 1 This article is part of the multi-disciplinary research project ‘Adaptations of Natural Resource-based Communities to Climatic and Societal Changes: Sami Reindeer Herding in the Past, Present and Future’ funded by The Swedish Research Council, FORMAS, The National Space Board and Faculty of Humanities, Umeå University. investigates hydropower development in the northern parts of Sweden, and how the reindeer husbandry of the indigenous Sami people was involved, through a case study of three hydropower projects in the early 20th century. An additional perspective is illuminated: how early hydroelectric development in the reindeer grazing areas was made possible through an immersed colonialism.

The combination of chemotherapy and photodynamic therapy has emerged as a promising strategy for cancer therapy due to its synergistic effects. In this work, PEGylated silver nanoparticles decorated with graphene quantum dots (Ag-GQDs) were tested as a platform to deliver a chemotherapy drug and a photosensitizer, simultaneously, in chemo-photodynamic therapy against HeLa and DU145 cancer cells in vitro. Ag-GQDs have displayed high efficiency in delivering doxorubicin as a model chemotherapy drug to both cancer cells. The Ag-GQDs exhibited a strong antitumor activity by inducing apoptosis in cancer cells without affecting the viability of normal cells. Moreover, the Ag-GQDs exhibited a cytotoxic effect due to the generation of the reactive singlet oxygen upon 425 nm irradiation, indicating their applicability in photodynamic therapy. In comparison with chemo or photodynamic treatment alone, the combined treatment of Ag-GQDs conjugated with doxorubicin under irradiation with a 425 nm lamp significantly increased the death in DU145 and HeLa. This study suggests Ag-GQDs as a multifunctional and efficient therapeutic system for chemo-photodynamic modalities in cancer therapy.

PURPOSE: Current antiretroviral regimens recommended for treatment-naïve patients include 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs). The purpose of this study is to evaluate whether a new NRTI-sparing regimen may provide an alternative for persons for whom traditional regimens may not be the best option. METHODS: PROGRESS is a 96-week, randomized, open-label, multicenter trial comparing the efficacy and safety of a boosted protease inhibitor (PI) and an integrase inhibitor (lopi-navir/ritonavir [LPV/r] + raltegravir [RAL]) to a boosted PI and 2 NRTIs (LPV/r + tenofovir/ emtricitabine [TDF/FTC]) in antiretroviral (ARV)-naïve HIV-1-infected adults. RESULTS: A total of 206 subjects were randomized to receive LPV/r + RAL (n=101) or LPV/r + TDF/FTC (n=105) and analyzed for ARV efficacy using the US Food and Drug Administration time to loss of virologic response (FDA-TLOVR) algorithm. The percentage of subjects with plasma HIV-1 RNA <40 copies/mL at week 48 was 83.2% in the LPV/r + RAL group and 84.8% in the LPV/r + TDF/FTC group (P = .850; difference -1.6%; exact 95% CI, -12.0% to 8.8%). As the lower limit of the exact 95% CI for the difference between regimens was at or above the protocol-defined threshold of -20% (as well as the more stringent threshold of -12%), LPV/r + RAL was noninferior to LPV/r + TDF/FTC. The occurrence of treatment-related, moderate/severe adverse events was similar between treatment groups through 48 weeks of treatment. CONCLUSIONS: The HIV treatment regimen of LPV/r + RAL resulted in noninferior efficacy and comparable safety and tolerability compared with a traditional NRTI-containing regimen through 48 weeks of treatment. These results support further evaluation of the LPV/r + RAL regimen.

The purpose of this study is to present the surgical and functional results of a total calcanectomy procedure as a foot salvage alternative in patients with extensive chronic osteomyelitis of the calcaneus. A retrospective review identified eight patients treated with a total calcanectomy for a chronic nonhealing plantar ulcer of the heel and osteomyelitis of the calcaneus. The primary diagnosis was insulin-dependent diabetes mellitus (six patients), pneumococcal septicemia (one patient), and an open calcaneal fracture (one patient). The average age of the patients was 52 years. Prior procedures included irrigation and debridement of the heel ulcer (seven patients), partial calcanectomy (three patients), and split thickness skin grafting (two patients). The vascular status of each limb was assessed preoperatively. Distal extremity bypass surgery was performed on two patients before calcanectomy. Osteomyelitis of the calcaneus was diagnosed by magnetic resonance imaging alone in three patients, and by technetium/indium scans and magnetic resonance imaging in five patients. The average follow-up duration was 27.3 months (range, 6-57 months). Infection at the plantar heel was controlled in all patients. In all eight cases the incisions were closed primarily. During a prolonged time of total contact casting to facilitate wound healing, one patient developed an anterior tibial ulcer that progressed to osteomyelitis and underwent below-knee amputation. Talonavicular subluxation occurred as a late complication in one patient. This was treated with a talonavicular arthrodesis and subsequent bracing for a nonunion. An assessment of functional ambulation was performed on all eight patients. Four patients maintained the same ambulation level postoperatively in a modified heel-containment orthosis. Two patients decreased one functional ambulation level, and one patient decreased two levels. One patient underwent below-knee amputation and is currently ambulatory with a prothesis. Assessment of ankle strength and range of motion of the surgical limb demonstrated decreased dorsiflexion and plantarflexion strength and a variable range of motion compared to the contralateral limb. Total calcanectomy is an alternative procedure to transtibial amputation in patients with chronic osteomyelitis of the calcaneus. Eradication of infection and preservation of the functional ambulation is achieved.

The different hydrocelectomy techniques are described and classified in 3 basic groups. The findings of a prospective randomized study in 87 patients, using representative techniques from each group, reveal that operations in which no dissection or excision of the parietal vaginalis is done are superior since they have less postoperative complications and achieve the same results.

An abstract is not available for this content so a preview has been provided. Please use the Get access link above for information on how to access this content.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare, potentially fatal disorder characterized by fever, pancytopenia, hepatosplenomegaly, and increased serum ferritin. HLH is being increasingly reported as a complication of dengue, a common tropical acute febrile illness. METHODOLOGY/PRINCIPAL FINDINGS: After a cluster of pediatric dengue-associated HLH patients was identified during the 2012-2013 dengue epidemic in Puerto Rico, active surveillance and a case-control investigation was conducted at four referral hospitals to determine the incidence of HLH in children and identify risk factors for HLH following dengue. Patients with dengue-associated HLH (cases) were matched by month of illness onset and admission hospital to dengue patients that did not develop HLH (controls). During 2008-2013, a total of 33 HLH patients were identified, of which 22 (67%) were associated with dengue and 1 died (dengue-associated HLH case-fatality rate: 4.5%). Two patients with dengue-associated HLH had illness onset in 2009, none had illness onset during the 2010 dengue epidemic, and 20 had illness onset during the 2012-2013 epidemic. Frequency of infection with either dengue virus (DENV)-1 or DENV-4 did not differ between cases and controls. Cases were younger than controls (median age: 1 vs. 13 years, p < 0.01), were hospitalized longer (18 vs. 5 days, p < 0.01), and were admitted more frequently to pediatric intensive care units (100% vs. 16%, p < 0.01). Cases had co-infection (18.2% vs. 4.5%, p = 0.04), recent influenza-like illness (54.5% vs. 25.0%, p = 0.01), and longer duration of fever (7 vs. 5 days; p < 0.01). Cases were more likely to have lymphadenopathy, hepatomegaly, splenomegaly, anemia, and elevated liver transaminases (p ≤ 0.02). CONCLUSIONS/SIGNIFICANCE: During this cluster of dengue-associated HLH cases that was temporally associated with the 2012-2013 epidemic, most patients with dengue-associated HLH were infants and had higher morbidity than dengue inpatients. Physicians throughout the tropics should be aware of HLH as a potential complication of dengue, particularly in patients with anemia and severe liver injury.

BACKGROUND AND PURPOSE: Endourology has evolved rapidly for the management of both benign and malignant disease of the upper urinary tract. Limited data exist, however, on the occupational hazards posed by complex endourologic procedures. The aim of this study was to determine the prevalence and possible causes of hand problems among endourologists who routinely perform flexible ureteroscopy compared with controls. MATERIALS AND METHODS: An online computer survey targeted members of the Endourological Society and psychiatrists in academic and community settings. A total of 600 endourologists and 578 psychiatrists were contacted by e-mail. Invited physicians were queried regarding their practice settings and symptoms of hand pain, neuropathy, and/or discomfort. RESULTS: Survey responses were obtained from 122 (20.3%) endourologists and 74 (12.8%) psychiatrists. Of endourologists, 61% were in an academic setting and 70% devoted their practice to endourology. Endourologists were in practice for a mean 13 years, performing 4.5 ureteroscopic cases per week with a mean operative time of 50 minutes. Hand/wrist problems were reported by 39 (32%) endourologists compared with 14 (19%) psychiatrists (P=0.0486, relative risk [RR]=1.69). Surgeons who preferred counterintuitive ureteroscope deflection were significantly more likely to have problems (56%) compared with intuitive users (27%) (RR 2.07, P=0.0139) or those with no preference (26%) (RR 2.15, P=0.0451). Overall, most respondents (85%) with hand/wrist problems needed either medical or surgical intervention. CONCLUSIONS: Hand and wrist problems are very common among endourologists. Future studies are needed to develop more ergonomic platforms and thereby reduce the endourologist's exposure to these occupational hazards.

We performed a systematic study of the bactericide and bacterial anti-adhesive properties of nanocrystalline diamond (NCD) and microcrystalline diamond (MCD) in comparison to other important industrial materials, such as copper, silver, polyethylene (Poly), and stainless steel (SS). The data show that NCD has better bactericide and bacterial anti-adhesive activity than Ag, but not as good as Cu. MCD, on the other hand, does not appear to have significant anti-bacterial activity. The superlative properties of NCD, such as mechanical hardness, resistance to oxidation and corrosion, and biological compatibility with blood and tissue, enable its use as antibacterial coating for medical implants. This is an application that cannot be achieved by Cu, which is known to be a highly effective antibacterial material but is not biocompatible. We also discuss possible underlying mechanisms to help understand the bactericide and bacterial anti-adhesive properties of the NCD surface.

A detailed mathematical model is developed to predict the heat and mass transfer performance of a vapour compression/liquid desiccant hybrid cooling and dehumidification absorber referred to as RCLDA system in this work. An RCLDA system uses a desiccant loop to bring the humidity within the comfort range along with a sensible cooling loop to bring the temperature within the comfort range. In an attempt to increase both the COP of the desiccant as well as the cooling system, the RCLDA system combines a desiccant cycle operating in its most efficient range along with a cooling cycle operating at higher evaporator temperatures. Governing equations describing the steady-state, two-dimensional heat and mass transfer in an RCLDA system are developed to study its cooling and dehumidification performance. A numerical scheme based on a control volume analysis is used to solve these differential equations. A parametric analysis is conducted to help understand and optimize the performance of this RCLDA system. The analytical model is also used to develop heat and mass transfer performance maps for partial load performance estimation of the RCLDA system. A knowledge of the partial load performance is required for the yearly performance estimation. It is found from this study that the performance of the RCLDA system is a strong function of refrigerant and air side NTU, evaporator temperature, carry-over regenerator load and refrigerant and air mass flow rates. The mass flow rate of desiccant solution in the absorber did not have any significant impact on the performance of the absorber. © 1998 John Wiley & Sons, Ltd.

Se examina la correlacion que existe entre dos variables fonologicas y tres variables estilisticas en el espanol de Puerto Rico. Las variables estilisticas que se tomaron en consideracion son la situacion (entrevista individual, conversacion en grupo y una presentacion oral), el discurso y la relacion que existe entre hablante e interlocutor. Se concentra en el habla de 20 jovenes adultos que residen en Caguas, Puerto Rico. Las variables fonologicas que se seleccionaron para este estudio son la vibrante multiple (rr) y la vibrante simple (r) en posicion de final de silaba. Los resultados se sometieron al programa estadistico VARBRUL y las conclusiones muestran la importancia que tienen las variables estilisticas en la investigacion sociolinguistica.

BACKGROUND: General recommendations for a reference case for economic studies in rheumatic diseases were published in 2002 in an initiative to improve the comparability of cost-effectiveness studies in the field. Since then, economic evaluations in osteoarthritis (OA) continue to show considerable heterogeneity in methodological approach. OBJECTIVES: To develop a reference case specific for economic studies in OA, including the standard optimal care, with which to judge new pharmacologic and non-pharmacologic interventions. METHODS: Four subgroups of an ESCEO expert working group on economic assessments (13 experts representing diverse aspects of clinical research and/or economic evaluations) were charged with producing lists of recommendations that would potentially improve the comparability of economic analyses in OA: outcome measures, comparators, costs and methodology. These proposals were discussed and refined during a face-to-face meeting in 2013. They are presented here in the format of the recommendations of the recently published Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement, so that an initiative on economic analysis methodology might be consolidated with an initiative on reporting standards. RESULTS: Overall, three distinct reference cases are proposed, one for each hand, knee and hip OA; with diagnostic variations in the first two, giving rise to different treatment options: interphalangeal or thumb-based disease for hand OA and the presence or absence of joint malalignment for knee OA. A set of management strategies is proposed, which should be further evaluated to help establish a consensus on the "standard optimal care" in each proposed reference case. The recommendations on outcome measures, cost itemisation and methodological approaches are also provided. CONCLUSIONS: The ESCEO group proposes a set of disease-specific recommendations on the conduct and reporting of economic evaluations in OA that could help the standardisation and comparability of studies that evaluate therapeutic strategies of OA in terms of costs and effectiveness.