Host availability affects the interaction between pupal parasitoid Coptera haywardi (Hymenoptera: Diiapridae) and larval-pupal parasitoid Diachasmimorpha longicaudata (Hymenoptera: Braconidae).

The use of multiple species in biological control programmes is controversial when interactions among them are not fully understood. We determined the response of the pupal parasitoid Coptera haywardi (Oglobin) to different availability of Anastrepha ludens (Loew) pupae previously parasitized or not by larval-pupal Diachasmimorpha longicaudata (Ashmead). The two types of pupae were exposed at different ages and proportions to different numbers of C. haywardi females for 48 h. The performance of C. haywardi adults emerging from parasitized and unparasitized pupae was measured. Coptera haywardi prefers to attack unparasitized A. ludens pupae rather than pupae parasitized by D. longicaudata. However, when the availability of unparasitized pupae was low or the number of foraging females was high, C. haywardi competed against early immature stages of the D. longicaudata, or hyperparasitized, feeding directly on the advanced-immature developmental stages of the early acting species. Adults of C. haywardi emerging as hyperparasitoids were no different in size, fecundity and longevity from those emerging as primary parasitoids. Our data suggest that simultaneous use of these species in augmentative biological control projects may be feasible but should be carefully planned in order to avoid any detrimental effect of its interaction.

Identification of Interleukin-27 (IL-27)/IL-27 Receptor Subunit Alpha as a Critical Immune Axis for In Vivo HIV Control.

Intact and broad immune cell effector functions and specific individual cytokines have been linked to HIV disease outcome, but their relative contribution to HIV control remains unclear. We asked whether the proteome of secreted cytokines and signaling factors in peripheral blood can be used to discover specific pathways critical for host viral control. A custom glass-based microarray, able to measure >600 plasma proteins involved in cell-to-cell communication, was used to measure plasma protein profiles in 96 HIV-infected, treatment-naive individuals with high (>50,000) or low (<10,000 HIV RNA copies/ml) viral loads. Univariate and regression model analysis demonstrate that plasma levels of soluble interleukin-27 (IL-27) are significantly elevated in individuals with high plasma viremia (P < 0.0001) and are positively correlated with proviral HIV-DNA copy numbers in peripheral blood mononuclear cells (PBMC) (Rho = 0.4011; P = 0.0027). Moreover, soluble IL-27 plasma levels are negatively associated with the breadth and magnitude of the total virus-specific T-cell responses and directly with plasma levels of molecules involved in Wnt/ß-catenin signaling. In addition to IL-27, gene expression levels of the specific IL-27 receptor (IL27RA) in PBMC correlated directly with both plasma viral load (Rho = 0.3531; P = 0.0218) and the proviral copy number in the peripheral blood as an indirect measure of partial viral reservoir (Rho = 0.4580; P = 0.0030). These results were validated in unrelated cohorts of early infected subjects as well as subjects before and after initiation of antiretroviral treatment, and they identify IL-27 and its specific receptor as a critical immune axis for the antiviral immune response and as robust correlates of viral load and proviral reservoir size in PBMC.IMPORTANCE The detailed knowledge of immune mechanisms that contribute to HIV control is a prerequisite for the design of effective treatment strategies to achieve HIV cure. Cells communicate with each other by secreting signaling proteins, and the blood is a key conduit for transporting such factors. Investigating the communication factors promoting effective immune responses and having potentially antiviral functions against HIV using a novel focused omics approach ("communicome") has the potential to significantly improve our knowledge of effective host immunity and accelerate the HIV cure agenda. Including 140 subjects with variable viral loads and measuring the plasma levels of >600 soluble proteins, our data highlight the importance of Th17 cells and Wnt/ß-catenin signaling in HIV control and especially identify the IL-27/IL-27 receptor subunit alpha (IL-27RA) axis as a predictor of plasma viral load and proviral copy number in the peripheral blood. These data may provide important guidance to therapeutic approaches in the HIV cure agenda.

Two different R gene loci co-evolved with Avr2 of Phytophthora infestans and confer distinct resistance specificities in potato.

Late blight, caused by the oomycete pathogen Phytophthora infestans, is the most devastating disease in potato. For sustainable management of this economically important disease, resistance breeding relies on the availability of resistance (R) genes. Such R genes against P. infestans have evolved in wild tuber-bearing Solanum species from North, Central and South America, upon co-evolution with cognate avirulence (Avr) genes. Here, we report how effectoromics screens with Avr2 of P. infestans revealed defense responses in diverse Solanum species that are native to Mexico and Peru. We found that the response to AVR2 in the Mexican Solanum species is mediated by R genes of the R2 family that resides on a major late blight locus on chromosome IV. In contrast, the response to AVR2 in Peruvian Solanum species is mediated by Rpi-mcq1, which resides on chromosome IX and does not belong to the R2 family. The data indicate that AVR2 recognition has evolved independently on two genetic loci in Mexican and Peruvian Solanum species, respectively. Detached leaf tests on potato cultivar 'Désirée' transformed with R genes from either the R2 or the Rpi-mcq1 locus revealed an overlapping, but distinct resistance profile to a panel of 18 diverse P. infestans isolates. The achieved insights in the molecular R - Avr gene interaction can lead to more educated exploitation of R genes and maximize the potential of generating more broad-spectrum, and potentially more durable control of the late blight disease in potato.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with early breast cancer.

The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with early breast cancer were updated and published online in 2023, and adapted, according to previously established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with early breast cancer. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with breast cancer representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), co-ordinated by ESMO and KSMO. The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different Asian regions represented by the 10 oncological societies. The latter are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with early breast cancer across the different regions of Asia, drawing on the evidence provided by both Western and Asian trials, whilst respecting the differences in screening practices, molecular profiling, as well as the age and stage at presentation. Attention is drawn to the disparity in the drug approvals and reimbursement strategies, between the different regions of Asia.

[Mandibular distraction osteogenesis in patients with craniofacial malformation]. / Distracción mandibular osteogénica en pacientes con malformaciones craneofaciales.

Craniofacial malformations (Pierre-Robin sequence, Treacher-Collins syndrome, Nager syndrome, etc.) are frequently associated to severe mandibular hypoplasia, which can cause upper airway obstruction by retroposition of the base of the tongue in the posterior pharyngeal space. Most of the patients respond to postural treatment. In prone decubitus position, it may be necessary to monitor oxygen saturation, insert a nasopharyngeal tube and even an endotracheal one. In more severe cases with prolonged and frequent pauses of apnea, tracheostomy may be necessary, but it is associated with high morbidity and sometimes mortality. In the last two years, in the Multidisciplinary Cleft Lip and Palate Unit of the Hospital Virgen de las Nieves, 4 children with severe obstructive apnea secondary to severe mandibular hypoplasia have been treated with mandibular distraction osteogenesis, this procedure being effective in the resolution of the condition. It has avoided tracheostomy, it has lengthened the jaw in a period of 2-3 weeks. During this time, the obstructive respiratory problems and also swallowing problems have disappeared. The esthetic results were excellent and the complications, for the moment, minimum.

[Generation of a substitute for human oral mucosa and verification of its viability by tissue-engineering]. / Generación de un sustituto de mucosa oral humana y comprobación de su viabilidad mediante ingeniería tisular.

Reconstruction of large oral mucosa defects is often challenging, since the shortage of healthy oral mucosa to replace the excised tissues. This way, tissue ingineering techniques may provide a source of autologous tissues available for transplant in these patients. In this work, we have developed a new model for artificial oral mucosa generated by tissue engineering using a fibrin-agarosa scaffold. For that purpose, we have generated primary cultures of human oral mucosa fibroblasts and keratinocytes from small biopsies of normal mucosa oral using enzymatic treatments. Then, we have determined the viability of cultured cells by electron probe quantitative X-ray microanalysis, and we have demonstrated that most of the cells in the primary cultures were alive and hd high K/Na ratios. Once cell viability was determined, we used cultured fibroblasts and keratinocytes to develop an artificial oral mucosa construct by using a fibrin-agarosa extracellular matrix and a sequential culture technique using porous culture inserts. Histological analysis of the artificial tissues showed high similarities with normal oral mucosa controls. The epithelium of the oral substitutes had several layers, with desmosomes and apical microvilli and microplicae. Both the controls and de oral mucosa substitutes showed high suprabasal expression of cytokeratin 13 and low expression of cytokeratin 10. All these results suggest that our model of oral mucosa using fibrin-agarose scaffolds show several similarities with native human oral mucosa.

Best Timing to Determine Field Parasitism by Released Diachasmimorpha longicaudata (Hymenoptera: Braconidae) Against Anastrepha (Diptera: Tephritidae) Pest Populations.

Our objective was to determine the timing of the highest parasitic activity by released Diachasmimorpha longicaudata (Ashmead) (Hymenoptera: Braconidae) in areas with fruits of sour orange and hog plums infested by Anastrepha ludens (Loew) and Anastrepha obliqua (McQuart) (Diptera: Tephritidae), under shaded and sunny conditions. Percent parasitism along fruit sampling period was related to host availability, which was influenced by the fruit size rather than environmental conditions. The highest parasitism in sour orange was obtained just the first day after release, but in hog plums this was observed during the first 3 days without significant differences between them. The levels of fruit infestation and parasitism were higher in shaded trees in sour orange as in hog plums. The high availability of larvae and the small size of hog plums were decisive for obtaining high levels of parasitism and keeping parasitoids near the release points. By contrast, the size and thick rind of sour orange provided to the larvae a physical refuge that was associated with lower parasitism, causing that parasitoids spread out in search of hosts more accessible. In sour orange, parasitism was exclusively by D. longicaudata, while in hog plums, we additionally found the coexistence of four native parasitoid species. This information suggests that in sour orange, the sampling should be performed 1 day after release, while in hog plums, the samplings can be extended to within the first 3 days. Such sampling can serve to better estimate the effect of D. longicaudata releases against Anastrepha pest populations in different fruit types.

Safety and Efficacy of Dolutegravir Plus Rilpivirine in Treatment-Experienced HIV-Infected Patients: The DORIVIR Study.

OBJECTIVES: To analyze the efficacy and safety of dolutegravir/rilpivirine (DTG/RPV) in HIV-infected patients who switched from any other antiretroviral therapy (ART). METHODS: Open-label, multicenter study including patients who switched to DTG/RPV between February 2015 and February 2016. Efficacy (HIV RNA <50 copies/mL), adverse events, and metabolic changes at 24 weeks were analyzed. RESULTS: A total of 104 participants were included, who switched for the following reasons: toxicity/intolerance (42.3%), convenience (27.8%), and drug interactions (17.3%). Prior regimens are protease inhibitor (56.7%), integrase strand transfer inhibitor (26.9%), and non-nucleoside reverse transcriptase inhibitor (16.3%). Efficacy at 24 weeks was 88.4% (intention to treat) and 96.8% (per protocol). Triglyceride levels were reduced, on average, by 12.7% and a mean decrease of 9.0% in the glomerular filtration rate was observed as well ( P values of .003 and .002, respectively), whereas total cholesterol, HDL cholesterol, LDL cholesterol, creatinine, and glutamic-pyruvic transaminase remained unchanged. No patient discontinued due to adverse events. CONCLUSIONS: Dolutegravir/RPV is effective and safe in long-term HIV-infected patients under any prior ART. Toxicity, convenience, and interactions were the main reasons for changing. At 24 weeks, the lipid profile improved with a decrease in triglycerides.

Regulation of immunophenotype modulation of monocytes-macrophages from M1 into M2 by prostate cancer cell-culture supernatant via transcription factor STAT3.

BACKGROUND: Transcription factor STAT3 has a prominent innate immunity effect on cancer progression. We determined the regulation of STAT3 in the immunophenotype modulation of macrophages from M1 into M2 induced by the cell-culture supernatant of the Prostate-Cancer line PC3. METHODS: Monocytes-macrophages from healthy donors were cultured in the supernatant of PC3 cells, membrane proteins, and intracytoplasmic and phosphorylated STAT3 were measured using flow cytometry, while cytokines and growth factors were studied using luminescence. Cytotoxicity and nitric oxide were evaluated via colorimetric assays. RESULTS: The supernatant of PC3 prostate-tumor cells effectively induced macrophages toward an M2 profile, and the expression of phosphorylated STAT3 in the monocytes-macrophages notably increased, and mainly related to IL-10. In the group of monocytes-macrophages treated with a STAT3 inhibitor, the macrophages were induced toward an M1 phenotype. CONCLUSIONS: In this study, we showed that the secretion profile of PC3 prostate-cancer cells induces a change in macrophage phenotype from M1 into M2, and that the phenomenon is related to phosphorylation of transcription factor STAT3 and IL-10.

Umbilical cord blood-derived stem cells spontaneously express cardiomyogenic traits.

BACKGROUND: Umbilical cord blood (UCB) has been widely used for hematopoietic stem cell transplantation. The UCB-derived stem cells (UCBSCs) have been proposed as an alternative to bone marrow (BM)-derived mesenchymal stem cells (MSCs) for cardiac cell-based therapy. Herein we studied whether UCBSCs spontaneously exhibit cardiac-specific markers in vitro. METHODS: Human UCBSCs were isolated, expanded, and phenotyped by flow cytometry, quantitative RT-PCR, and immunofluorescence. Cell pluripotency and proliferation were also assessed by adipogenic and osteogenic media and in growth assays. RESULTS: Among 25 analyzed UCB, 16% of cases afforded primary culture satisfactory generation of UCBSCs. Duplication time (Td) of cultures was 2.16 +/- 0.06 days. The cells were strongly positive for CD105 (18.5 +/- 0.14), CD44 (27 +/- 2.8), CD166 (13 +/- 9), CD29 (59 +/- 9.4), CD90 (60 +/- 11) and consistently negative for CD117 (1.2 +/- 0.1), CD106 (1.1 +/- 0), CD34 (1.2 +/- 0.2), CD14 (1 +/- 0), and CD45 (1 +/- 0), consistent with a mesenchymal lineage. Adipogenesis and osteogenesis of cells resulted in low accumulation of intracellular lipid droplets and high deposition of calcium. The UCBSCs showed gene transcripts for alpha-actinin, connexin (Cx)-43, SERCA-2, and stromal cell-derived factor (SDF)-1alpha. At the protein level, the cells abundantly expressed alpha-actinin, Cx-43, SERCA-2 and SDF-1alpha. In contrast, these cells did not express the cardiac transcription factors GATA-4, Tbx5, and Nkx2.5, nor the sarcomeric proteins beta-myosin heavy chain (beta-MyHC) or cardiac troponin I (cTnI). CONCLUSIONS: Human UCBSCs may represent an alternative source of stem cells for myocardial-cell replacement. These cells can be highly expanded. They spontaneously express proteins of paramount importance for cardiovascular regeneration, such as Cx-43, SERCA-2, and SDF-1alpha.

Vaginal Cuff Dehiscence Presenting with Free Air 60 Days after Robotic-Assisted Hysterectomy.

INTRODUCTION: The vast majority of patients presenting with pneumoperitoneum have visceral organ perforation and require urgent diagnostic laparoscopy. Nonsurgical causes are relatively rare and may be attributed to multiple etiologies. CASE PRESENTATION: Here we describe the case of a 38-year-old Caucasian female who presented to the emergency department with three days of cramping, epigastric abdominal pain. Her physical exam was notable for tenderness to palpation in the epigastric area and abdominal and chest X-rays showed free air under the diaphragm. Free air around the porta hepatis was verified on CT scan. Approximately 90% of pneumoperitoneum cases are due to perforation of visceral organs and therefore require operative management. An urgent exploratory laparoscopy revealed no clear source of free air, but postoperatively the patient developed a large volume of watery discharge from her vagina. Subsequent workup revealed a 1 cm vaginal cuff dehiscence which was later repaired with no postoperative complications. CONCLUSION: Although the majority of patients with pneumoperitoneum require urgent exploratory laparoscopy, a careful diagnostic workup may reveal sources of free air that are not related to hollow viscous perforation. Vaginal cuff dehiscence represents a rare yet nonurgent source of pneumoperitoneum. This differential should be considered in light of the possible intra- and postoperative complications of surgery.

Healthcare seeking for constipation: a population-based survey in the Mediterranean area of Spain.

BACKGROUND: The use of healthcare resources for the management of constipation is not well-known. AIM: To analyse healthcare seeking for constipation, defined by three different criteria, and its related factors and to assess the frequency of use of laxatives, suppositories and enemas for the treatment of constipation. METHODS: A cross-sectional study in the general community. A questionnaire comprising 21-items was developed and delivered by mail to a random sample of 506 subjects aged 18-65 years, and belonging to a Spanish population. RESULTS: Seeking of health care was high in the sample (16%) and was similar for all definitions of constipation (over 40% of constipated subjects). It was associated with female gender, a higher educational level and two symptoms, such as prolonged defecation and abdominal pain. A 14% of the sample used laxatives, and about a 25% of constipated subjects used laxatives at least once a week. Utilization was more frequent in women, with no differences by age group. CONCLUSIONS: Chronic constipation is a problem that causes an important consumption of resources in our setting, derived from laxative use and the seeking of medical help to combat the problem. The use of these resources is higher in women.

[Single-port video-assisted thoracic surgery in an awake patient]. / Cirugía torácica asistida por vídeo uniportal en paciente despierto.

Video-assisted thoracic surgery is traditionally carried out with general anaesthesia and endotracheal intubation with double lumen tube. However, in the last few years procedures, such as lobectomies, are being performed with loco-regional anaesthesia, with and without sedation, maintaining the patient awake and with spontaneous breathing, in order to avoid the inherent risks of general anaesthesia, double lumen tube intubation and mechanical ventilation. This surgical approach has also shown to be effective in that it allows a good level of analgesia, maintaining a correct oxygenation and providing a better post-operative recovery. Two case reports are presented in which video-assisted thoracic surgery was used, a lung biopsy and a lung resection, both with epidural anaesthesia and maintaining the patient awake and with spontaneous ventilation, as part of a preliminary evaluation of the anaesthetic technique in this type of surgery.

Abnormal mRNA splicing resulting from consensus sequence splicing mutations of ATP7B.

More than 200 Wilson disease (WD) disease-causing mutations have been defined to date. Missense mutations are largely prevalent while splice-site mutations are limited in number. Most reside in the splice donor or acceptor sites and only a minority are detected in splicing consensus sequences. Furthermore, only a few splicing mutations have been studied at the RNA level to date. In this study, using the RT-PCR method we performed the molecular characterization of four consensus splice-site mutations identified by DNA analysis in patients with WD. One of them, previously described 1707+3insT, occurred at position 3 in the donor splice site of intron 4, while the other three, 2122-8T>G, 2866-6T>G, and 3061-12T>A, are novel and occurred in the acceptor splice sites of introns 7, 12, and 13, respectively. Analysis revealed a prevalently abnormal splicing in the samples carrying the mutations compared to the normal controls. Comparison of RNA splicing with normal controls in liver and lymphocytes further suggests that abnormal splicing of the WD gene is also present and differentially regulated in normal tissues. The results produced in this study strongly suggest that DNA mutations residing in the consensus sequence of WD gene splice sites result in the WD phenotype by interfering with the production of the normal WD protein. Further studies are necessary to better quantify the amount of different transcripts produced by these mutations, and establish their correlation with the disease phenotype.

Drug-resistant Mycobacterium tuberculosis and atypical mycobacteria isolated from patients with suspected pulmonary tuberculosis in Honduras.

BACKGROUND: Tuberculosis is a major health problem in Central America. In Honduras, with an incidence rate of 81/100,000, it is an increasingly common cause of morbidity and hospitalization. This study was conducted to examine drug-resistant tuberculosis and prevalence of infection with atypical mycobacteria in Honduran patients with suspected pulmonary tuberculosis. METHODS: Pulmonary specimens from 235 Honduran patients with suspected tuberculosis were examined by acid-fast smears and culture. The 95 mycobacterial strains isolated were identified to species level and drug susceptibility tests were carried out. Resistant Mycobacterium tuberculosis strains were tested for susceptibility to six additional drugs. Their possible relationship was studied by DNA restriction fragment length polymorphism. RESULTS: Drug-resistant strains were found in 13 of 85 culture-verified tuberculosis patients, including 10 with isolates of multidrug-resistant bacteria. Seven of the patients with multidrug-resistant tuberculosis had smear-positive disease. Nine of them had a history of specific therapy. Two patients with drug-resistant disease were shown to be infected by identical strains. Only one of 11 HIV-positive patients had drug-resistant tuberculosis. Most resistant strains were susceptible to ciprofloxacin, amikacin, kanamycin, and pyrazinamide. Atypical mycobacteria were isolated from 10 patients with suspected tuberculosis. Seven of them were receiving antituberculosis chemotherapy and five had smear-positive samples. CONCLUSIONS: These results illustrate the importance of mycobacterial culture and subsequent species identification and in vitro susceptibility testing for identification of patients with drug-susceptible or drug-resistant tuberculosis and those infected or colonized with other mycobacteria.

Improved sputum microscopy for a more sensitive diagnosis of pulmonary tuberculosis.

Diagnosis of tuberculosis in low-income countries is hindered by the low sensitivity of direct sputum smear microscopy. We compared an improved method based on liquefaction of sputum with NaOCl followed by centrifugation with standard direct smear in a central hospital and at peripheral health centres in Honduras. Specificity was high and sensitivity significantly better with the NaOCl method. Moreover, this technique is safe, inexpensive and easy to perform. We recommend its implementation to enable rapid, sensitive laboratory diagnosis of pulmonary tuberculosis, especially in resource-poor settings where culture is not possible.

Chronic nicotine and withdrawal effects on body weight and food and water consumption in female rats.

Female rats were used to examine the effects of chronic nicotine administration and withdrawal on food and water consumption and body weight. Rats with chronic nicotine pellet implants consumed significantly less food and water than controls for the first five days and then gradually returned to control levels of consumption. The lowest level of body weight was reached on day 9 after which there was a slow return to control weights by day 21. When the nicotine pellets were removed from the short-term exposure group on day 14, they showed significant hyperphagia and hyperdipsia and a very rapid weight gain for the next several days, which clearly outpaced the recovery of weight in the long-term nicotine exposure group. These results show that in female rats changes in weight during chronic nicotine administration and withdrawal are accompanied by changes in rates of consumption. In addition, nicotine withdrawal can cause hyperphagia and hyperdipsia even though levels of consumption had previously returned to control levels and even though the route of nicotine administration was not oral.

Achalasia-like syndrome as the first manifestation in a patient with CREST syndrome.

We report a case of oesophageal disease as the first manifestation in a patient with CREST syndrome. A 46-year-old man with achalasia-like syndrome developed CREST syndrome 4 years later. A pneumatic dilatation of the cardia was performed. After pneumatic dilatation the dysphagia and regurgitation disappeared but the patient developed reflux oesophagitis. Four years after diagnosis of oesophageal disease he presented with a clinical picture of CREST syndrome. An acute ileus and constipation developed later. After receiving medical therapy with omeprazole and cisapride the patient is free of oesophageal symptoms and bowel movements are normal. Oesophageal disease is common in patients with limited and diffuse scleroderma, but to our knowledge achalasia-like syndrome has not been previously described as the first manifestation of the systemic disease.

Is the prevalence of severe stenoses of left circumflex different from that of the right coronary artery?

We reviewed the last 911 coronary arteriograms performed in our laboratory because of chest pain. Among 215 patients with single-vessel disease, 40 had stenosis in the right coronary artery and 43 in the left circumflex. This finding conflicts with previous reports. Perhaps racial differences could explain this discrepancy.