Correction: Therapeutic targeting of Id2 reduces growth of human colorectal carcinoma in the murine liver.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Functional analysis of the Chloroplast GrpE (CGE) proteins from Arabidopsis thaliana.

The function of proteins depends on specific partners that regulate protein folding, degradation and protein-protein interactions, such partners are the chaperones and cochaperones. In chloroplasts, proteins belonging to several families of chaperones have been identified: chaperonins (Cpn60s), Hsp90s (Hsp90-5/Hsp90C), Hsp100s (Hsp93/ClpC) and Hsp70s (cpHsc70s). Several lines of evidence have demonstrated that cpHsc70 chaperones are involved in molecular processes like protein import, protein folding and oligomer formation that impact important physiological aspects in plants such as thermotolerance and thylakoid biogenesis. Despite the vast amount of data existing around the function of cpHcp70s chaperones, very little attention has been paid to the roles of DnaJ and GrpE cochaperones in the chloroplast. In this study, we performed a phylogenetic analysis of the chloroplastic GrpE (CGE) proteins from 71 species. Based on their phylogenetic relationships and on a motif enrichment analysis, we propose a classification system for land plants' CGEs, which include two independent groups with specific primary structure traits. Furthermore, using in vivo assays we determined that the two CGEs from A. thaliana (AtCGEs) complement the mutant phenotype displayed by a knockout E. coli strain defective in the bacterial grpE gene. Moreover, we determined in planta that the two AtCGEs are bona fide chloroplastic proteins, which form the essential homodimers needed to establish direct physical interactions with the cpHsc70-1 chaperone. Finally, we found evidence suggesting that AtCGE1 is involved in specific physiological phenomena in A. thaliana, such as the chloroplastic response to heat stress, and the correct oligomerization of the photosynthesis-related LHCII complex.

[Rapidly progressive dementia and parkinsonism associated to multiple dural arteriovenous fistulas]. / Demencia rapidamente progresiva y parkinsonismo asociados a multiples fistulas arteriovenosas durales.

INTRODUCTION: Rapidly progressive dementias are an infrequent group of diseases characterised by cognitive deterioration and other neurological disorders that develop over a period ranging from weeks to months. Their causation is varied and includes a large number of neurodegenerative, toxic, metabolic, autoimmune, infectious and vascular conditions. CASE REPORT: We report the case of a 69-year-old male who was admitted to hospital due to a rapidly progressive dementia and parkinsonism caused by multiple dural arteriovenous fistulas, which were successfully treated by means of endovascular therapy. CONCLUSION: Dural arteriovenous fistulas are anomalous connections between the dural arteries and the venous sinuses or cortical veins that are an unusual cause of rapidly progressive dementia. They must, however, be taken into account, given the availability of a specific treatment with reversal of the symptoms.

TITLE: Demencia rapidamente progresiva y parkinsonismo asociados a multiples fistulas arteriovenosas durales.Introduccion. Las demencias rapidamente progresivas son un grupo poco frecuente de enfermedades caracterizadas por un deterioro cognitivo y otras alteraciones neurologicas que evolucionan en el transcurso de semanas a meses. Su etiologia es diversa e incluye un gran numero de condiciones neurodegenerativas, toxicas, metabolicas, autoinmunes, infecciosas y vasculares. Caso clinico. Varon de 69 años, que ingreso por demencia rapidamente progresiva y parkinsonismo causado por multiples fistulas arteriovenosas durales tratadas exitosamente mediante terapia endovascular. Conclusion. Las fistulas arteriovenosas durales son conexiones anomalas entre las arterias durales y los senos venosos o venas corticales que constituyen una causa inusual de demencia rapidamente progresiva, pero que debe considerarse, dada la disponibilidad de un tratamiento especifico con reversion de los sintomas.

Diagnosis and New Treatment Modalities for Glioblastoma: Do They Improve Patient Survival?

Central nervous system (CNS) malignances include tumors of the brain and spinal cord. Taking into account the cell type where they originate from, there are almost 120 different types of CNS tumors. Benign tumors are not aggressive and normally do not invade other organs; however, they require surgical removal before they alter the surrounding brain functions. Primary malignant brain tumors commonly include astrocytomas, oligodendrogliomas, and ependimomas, where astrocytomas represent around 76%. The World Health Organization (WHO) has defined four histological grades of astrocytomas that range from the less aggressive tumors (grade I) to highly malignant tumors (grade IV). These grade IV tumors, also called glioblastoma (GBM), are the most aggressive of the primary malignant brain tumors. Patients with GBM have a median survival of 12 to 15 months. Current treatment for GBM includes surgery, radiotherapy and chemotherapy. Although there have been some advances in diagnosis and treatment, there is still no optimal treatment available for GBMs. In this review, we will discuss the approaches for GBM diagnosis and treatment, with a special emphasis to post-treatment imaging, and whether novel targeted therapies have impacted the survival of GBM patients. In addition, we will discuss clinical trials and the future of GBM diagnosis and treatment.

Epidemiology of HIV infection among prostitutes in the Philippines.

Between 1985 and 1987, examinations for human immune deficiency virus (HIV) antibody were done on 25,392 prostitutes working in 64 cities throughout the Philippines. The country-wide seropositivity rate among prostitutes based on this sample was 0.8/1,000. Of the HIV cases, 85% were working in just two cities whose prostitute populations comprised 50% of the total sample. The average incidence rate for the same two cities after 1 year was 2.3/1,000. HIV antibody-positive women were enrolled in a case-control study to determine demographic and epidemiologic risk factors. This study involving 34 HIV-positive prostitutes and 61 randomly selected negative control prostitutes did not reveal any risk factors related to sexual or other types of behavior. A history of genital warts, a history of abnormal vaginal discharge, and cytomegalovirus antibody were significantly more frequent in the HIV-positive cases than in the controls; however, by logistic regression analysis, only an abnormal vaginal discharge was independently associated with HIV infection. Absence of any evidence of transmission by blood transfusion or i.v. drug abuse suggests that HIV was introduced by the heterosexual route.

Efficacy of pravastatin as a hypolipidemic agent in patients with polygenic hypercholesterolemia.

In Mexico, hypercholesterolemia has become a major public health problem particularly in the states of the north of the country and in Mexico City, where a prevalence of 20% has been reported. Schemes of treatment have now been reinforced by the appearance of new cholesterol reducing drugs. The objective of the study was to demonstrate efficacy and safety of a 10 mg daily dose of oral Pravastatin (a new 3-hydroxy-3-methyl glutaryl CoA inhibitor) in a group of patients positive for hyperlipidemia, after 6 months of treatment. Twenty-five patients were included (14 men, 11 women) with an average age of 54 and 50 years, respectively. The main outcome measure was total cholesterol (T-CHOL), low density lipoprotein-cholesterol (LDL-C), triglycerides (TGL), high density lipoprotein cholesterol (HDL-C) and adverse drug reactions report. Twenty-one out of 25 patients completed the study. T-CHOL diminished 21%, LDL-C was reduced by 28%, TGL decreased 6% and HDL-C increased 32%. No adverse reactions were observed throughout the study. Our study shows that the use of a low dose of Pravastatin satisfactorily reduced T-CHOL and LDL-C levels while significantly increasing HDL-C after 27 weeks of treatment, without untoward effects.

HIV-1 seropositive women in the Philippines: pregnancy outcome and perinatal transmission of HIV-1.

Annual surveillance studies were initiated in 1985 to determine the incidence and prevalence of HIV-1 infection in female prostitutes registered through the Social Hygiene Clinic System of the Philippine Department of Health. All of the confirmed HIV-1 seropositive women detected in the above surveys who could be contacted were followed up about every three months to monitor their clinical and immunological status. Since we regularly interviewed and examined these HIV-1 seropositive women, we were able to note the occurrence of pregnancies following HIV diagnosis. By September 1990, 54 HIV-1 seropositive women (aged 18-35) detected from the above surveys had been interviewed and examined. Twenty-six of these HIV-1 positive women had a total of 37 pregnancies. Eight were pregnant at the time of HIV diagnosis: three term deliveries, one premature delivery (PD) at eight months, three abortions, and one lost to follow-up while still pregnant. Five of these eight had repeat pregnancies: two term deliveries, two abortions, and one lost to follow-up while pregnant. Eighteen other women became pregnant one or more times after HIV diagnosis: seven term deliveries, 13 abortions, two PDs, one ectopic pregnancy terminated, one currently pregnant, and one lost to follow-up during pregnancy. There was no clear indication from clinical examinations and CD4+ cell counts that pregnancy exacerbated the course of HIV-1 related disease in these women. One of the 12 term infants has died and eight have developed non-specific findings that are suggestive but not diagnostic of HIV infection.2+ strongly seropositive by both ELISA and Western blot assay at 16 months.

Sexual behavior of Filipino female prostitutes after diagnosis of HIV infection.

A study of female prostitutes in Manila who tested positive for human immunodeficiency virus (HIV) antibody ascertained demographic and sexual behavior information following diagnosis. Counselling alone did not appear to have a major impact on the sexual behavior of the HIV positive women since most continued to work as prostitutes. Switching from high risk to low risk jobs in bars is not effective in preventing HIV positive women from engaging in prostitution. Revoking work permits is only effective if enforced with adequate follow up. Alternative job training programs may offer a viable approach.

[Ileo-ileal and ileocecal invagination due to intestinal lipomatosis]. / Invaginación ileoileal e ileocecal por lipomatosis intestinal.

Intestinal lipomatosis is a rare entity and few cases have been reported in the literature. The condition is usually asymptomatic. Symptomatic cases usually present as obstruction or, less frequently, as bleeding. Intestinal barium studies, ultrasonography and computed tomography are useful diagnostic techniques. We present the case of a 47-year-old man with no relevant medical history who presented with intestinal obstruction of several months' duration. Complementary investigations yielded a diagnosis of intestinal obstruction due to ileocecal invagination secondary to endoluminal tumors of the ileum. Surgery and pathological analysis revealed the latter to be intestinal lipomatosis. This rare clinical entity has been associated with diverticulosis and intestinal volvulus.

Countertransference issues in the in-home treatment of child sexual abuse.

Strong emotions are aroused in people in the presence of child abuse. For the therapist trying to help abusive families, these feelings can destroy any prospect of achieving a therapeutic process. This problem is particularly acute in the in-home situation.

Desenlaces del tratamiento con una fórmula extensamente hidrolizada a base de suero en lactantes con alergia a la proteína de leche de vaca / Outcomes of treating infants with cow's milk protein allergies with an extensively hydrolyzed serum-based formula

Resumen Introducción: la alergia a la proteína de leche de vaca (APLV) es la alergia alimentaria más frecuente en el primer año de vida. La evidencia actual acerca de la respuesta a una fórmula extensamente hidrolizada (FEH) a base de suero es insuficiente. Objetivo: determinar los desenlaces clínicos en lactantes con APLV a una FEH a base de suero (Nutrilón Pepti Junior®). Metodología: estudio retrospectivo, tipo serie de casos. Se incluyeron lactantes (≤12 meses) con APLV valorados en la consulta externa entre enero de 2011 y octubre de 2015 en un servicio de gastroenterología pediátrica. La información de datos demográficos, manifestaciones digestivas, tiempo de inicio de síntomas, antropometría y respuesta clínica a la fórmula fue abstraída a partir de la revisión de la historia clínica. Se comparó el estado nutricional de los pacientes en la primera y en la consulta de control un año después utilizando la prueba t de Student. Resultados: se incluyeron 40 lactantes (42,5% varones) de 3,3 ± 2,4 meses, con síntomas como vómito/regurgitación, cólico/irritabilidad y deposición con sangre. Los antecedentes familiares y perinatales relacionados con el desarrollo de APLV fueron la ingesta de biberón en la primera semana de vida: 27 (67,5%), madre ≥30 años: 33 (82,5%), atopia en 2 familiares: 12 (30%) y parto por cesárea: 30 (75%). 37 (92,5%) pacientes mostraron una respuesta positiva a una FEH a base de suero, mientras que 3 (7,5%) pacientes no respondieron y requirieron una fórmula a base de aminoácidos (FAA) libres. Los z-score de peso/edad: -0,69 ± 1,03 y peso/talla: -0,79 ± 1,00 de la primera consulta mejoraron en el seguimiento posterior al año (p <0,05): peso/edad: -0,27 ± 0,98 y peso/talla: -0,14 ± 0,98. Conclusión: se encontró recuperación nutricional y tolerancia a la leche de vaca en un alto porcentaje de lactantes con APLV que recibieron una FEH a base de suero.

Abstract Introduction: Cow's milk protein allergies (CMPA) are the most frequent food allergies in the first year of life. Current evidence about responses to an extensively hydrolyzed serum based formula is insufficient. Objective: This study's objective was to determine clinical outcomes in infants with CMPA to an extensively hydrolyzed serum based formula (Nutrilón Pepti Junior®). Methodology: This is a retrospective case series study of infants 12 months old or younger diagnosed with CMPA in the outpatient clinic of a pediatric gastroenterology service between January 2011 and October 2015. Information including demographic data, digestive manifestations, time of onset of symptoms, anthropometry and clinical responses to formula was abstracted from a review of clinical histories. Patients' nutritional statuses at first and one year follow-up consultations were compared using Student's t-test. Results: Forty infants (42.5% males) whose average age was 3.3 ± 2.4 months were included. Their symptoms included vomiting/regurgitation, colic/irritability and bloody stools. Family and perinatal history related to the development of CMPA included bottle feeding in the first week of life (27 patients, 67.5%), mothers who were thirty years of age or older (33 patients, 82.5%), atopy in two family members (12 patients, 30 %) and cesarean deliveries (30 patients, 75%). Thirty-seven patients (92.5%) responded positively to an extensively hydrolyzed serum based formula while three patients (7.5%) did not respond and required a milk-free amino acid based formula. The first consultation z-score of P/E was -0.69 ± 1.03 while the first consultation z-score of P/T was -0.79 ± 1.00. These improved at the one year follow-up to (p <0.05) P/E: -0.27 ± 0.98 and P/T: -0.14 ± 0.98, respectively. Conclusion: Nutritional recovery and tolerance to cow's milk was found in a high percentage of infants with CMPA who received an extensively hydrolyzed serum based formula.

[How we treat subclinical hypothyroidism in our daily clinical practice]. / Cómo tratamos en nuestra práctica clínica diaria el hipotiroidismo subclínico.

OBJECTIVE: To study the therapeutic approach to subclinical hypothyroidism (HTS), the frequency of introducing replacement therapy, reasons for starting, doses, and duration, in the population over 14 years-old in a Primary Care Centre. MATERIAL AND METHODS: Longitudinal, retrospective observational study of 1156 patients with a hypothyroidism/myxedema episode (T86 in the International Classification of Primary Care (ICPC)) entered in the OMI program were studied. Excluded: 10 duplicates, 180 no inclusion criteria or inability to collect data, 25 diagnosed in another laboratory, 359 with clinical hypothyroidism (HTC). MEASUREMENTS: Sex, age, TSH value to diagnosis and initiate treatment, or latest TSH recorded in the clinical history (HC) if not treated, TSH diagnostic confirmation, antiTPO antibodies (ATAs), presence of fatigue, goitre, neuropsychiatric symptoms, raised cholesterol, if HTS secondary, progression to HTC, diagnostic-start treatment interval, initial and final dose, duration, reasons for discontinuation. RESULTS: 582 patients: 508 women. Mean age: 43.03 (sd 15.97). HTS treated: 330 (56.7%); TSH at diagnosis < 10: 81.6%; Mean TSH treated: 11.22 (sd 10.49); Made ATAs performed: 315 (54%),+166 (52.7%); Fatigue not recorded in HC: 64%; Goitre: 65%. 67% untreated: returned to normal spontaneously. Starting dose: 86% ≤ 50µg. Final ≤ 50: 43%. Treatment duration: 1-5 years 41%; > 5 years 40%. Immediate treatment after diagnosis 38%. Remain treated 93%. Variables that increase the likelihood of onset of treatment (Logistic Regression): TSH value (OR 32.5, CI 12.8- 82.6), ATAs+(OR 4.7, CI 2.8-7.7); Fatigue (OR 2.5, CI 1.5-4), Goitre (OR 3, CI 1.3-6.6). CONCLUSIONS: The decision to treat is generally adequate, but often becomes a chronic analytical disorder, because of unduly prolonged treatment without attempts to withdraw it. Clinical history and physical examination tend to be ignored.

Caracterización óptica del Sistema Nervioso Central de Haementeria officinalis / Optical characterization of the Central Nervous System of Haementeria officinalis

Resumen: La falla en la regeneración de las neuronas del sistema nervioso central (SNC) en vertebrados superiores es un problema que no se ha resuelto completamente, esto limita la rehabilitación de muchas conductas motoras después de una lesión en la médula espinal. En la regeneración neuronal intervienen múltiples factores y de estos, los que inducen el crecimiento neurítico se han estudiado para intentar favorecer la extensión y la reconexión de las neuronas lesionadas con sus blancos. La regeneración del SNC de sanguijuelas se ha estudiado intensamente porque permite abordar el problema a diferentes niveles con distintas técnicas, en este trabajo se obtuvo el espectro de absorción óptico, con espectroscopía fotoacústica (EFA), del SNC y de tejido de la sanguijuela Haementeria officinalis, con el objetivo de conocer las longitudes de onda óptimas para la irradiación posterior de células del SNC y de tejido H. officinalis. Los resultados de este estudio muestran que el SNC de estos organismos absorbe en la region comprendida de 300 nm a 500 nm, y las muestras de tejido tienen un máximo de absorción óptico proximo a 300 nm, además se observaron diferencias evidentes entre los espectros de absorción ópticos del SNC con lesión y el control (sin lesión).

Abstract: The failure in the neuron regeneration in the central nervous system (CNS) in higher vertebrates, is a not completely solved problem, this limits the rehabilitation of many motor conducts after an injury in the spinal cord. In neuronal regeneration multiple factors are involved, between them those that induce the neurite outgrowth which has been studied to try to encourage the extension and reconnection of the injury neurons with their blanks. The regeneration of the CNS of leeches has been intensely studied because allows to approach the problem at different levels with different techniques. In this study the optical absorption spectrum of the CNS and the tissue of the leech H. officinalis was obtained, by using photoacoustic spectroscopy (PAS), in order to investigate the optimal wavelenghts for later irradiation of CNS cells and tissue of H. officinalis. The results of this study show that the CNS of these organisms absorbs in the region of 300 nm to 500 nm, and the tissue samples has a maximun of optical absorption near to 300 nm, besides were observed evident differences between the optical absorption spectra of CNS with injury and the control (without injury).

MDA7: a novel selective agonist for CB2 receptors that prevents allodynia in rat neuropathic pain models.

BACKGROUND AND PURPOSE: There is growing interest in using cannabinoid type 2 (CB(2)) receptor agonists for the treatment of neuropathic pain. In this report, we describe the pharmacological characteristics of MDA7 (1-[(3-benzyl-3-methyl-2,3-dihydro-1-benzofuran-6-yl)carbonyl]piperidine), a novel CB(2) receptor agonist. EXPERIMENTAL APPROACH: We characterized the pharmacological profile of MDA7 by using radioligand-binding assays and in vitro functional assays at human cannabinoid type 1 (CB(1)) and CB(2) receptors. In vitro functional assays were performed at rat CB(1) and CB(2) receptors. The effects of MDA7 in reversing neuropathic pain were assessed in spinal nerve ligation and paclitaxel-induced neuropathy models in rats. KEY RESULTS: MDA7 exhibited selectivity and agonist affinity at human and rat CB(2) receptors. MDA7 treatment attenuated tactile allodynia produced by spinal nerve ligation or by paclitaxel in a dose-related manner. These effects were selectively antagonized by a CB(2) receptor antagonist but not by CB(1) or opioid receptor antagonists. MDA7 did not affect rat locomotor activity. CONCLUSION AND IMPLICATIONS: MDA7, a novel selective CB(2) agonist, was effective in suppressing neuropathic nociception in two rat models without affecting locomotor behaviour. These results confirm the potential for CB(2) agonists in the treatment of neuropathic pain.

Therapeutic targeting of Id2 reduces growth of human colorectal carcinoma in the murine liver.

During development inhibitor of DNA-bind-2 (Id2) regulates proliferation and differentiation. Id2 expression has been detected in cancer cells, yet its cellular function and validity as a therapeutic target remains largely unknown. Immunohistochemical analysis of colorectal cancer (CRC) specimens revealed that Id2 was undetectable in normal colonic mucosa, but occurs in 40% of primary tumors and in most CRC liver metastases (P<0.0001). Additionally, Id2 was expressed in all CRC cell lines assayed. CRC cells with reduced Id2 expression demonstrated reduced proliferation. Analysis of CRC cell cycle regulatory proteins showed that reducing Id2 levels reduces cyclin D1 levels and increased p21 levels. Reduction of Id2 expression also enhanced tumor cell apoptosis, increasing levels of the pro-apoptotic protein Bim/Bod, and cleavage of caspase-7 and poly (ADP-ribose) polymerase. In vivo studies show tumors derived from cells with decreased Id2 levels formed smaller tumors with fewer metastases compared with tumors with normal levels (P<0.05). Furthermore, intraperitoneal administration of Id2 small interfering RNA (siRNA) conjugated with the neutral liposome 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine decreased tumor burden in mice compared with control treatment (P=0.006). We conclude that Id2 is upregulated in CRC, and is important in promoting cell survival. In vivo targeting of Id2 by siRNA establishes that it is a valid therapeutic target where its expression occurs.

Bilateral seminoma 34 years after orchiopexy.

A case of bilateral seminoma in a 59-year-old patient who had undergone bilateral orchiopexy 34 years previously is presented. To our knowledge this is the longest interval between an orchiopexy and diagnosis of bilateral malignancy.

Effect of antibiotics on the prevalence of enterotoxigenic Escherichia coli in two populations in the Philippines.

Hostesses and restaurant employees in the Philippines were studied to determine whether an increased use of antibiotics was associated with a higher point prevalence of enterotoxigenic Escherichia coli. Of 1,030 hostesses and 628 restaurant employees, 28 and 4%, respectively, said that they had taken antibiotics within a week of being cultured (P less than 0.001). Of hostesses and restaurant employees, 10% (103 of 1,030) and 2% (14 of 628), respectively, had antibiotics detectable in their urine (P less than 0.001). Enterotoxigenic E. coli strains were isolated from 1.2% (12 of 1,030) of hostesses and 1.7% (11 of 628) of restaurant employees. In both populations, enterotoxigenic E. coli strains were never found in subjects who had antibacterial activity in their urine. Although resistance to two or more antibiotics was found more frequently in E. coli isolated from hostesses than in that isolated from restaurant workers (48 versus 33%; P less than 0.01), antibiotic selective pressure did not increase the prevalence of enterotoxigenic E. coli in these two populations.

Inhibition of human topoisomerase II by anti-neoplastic benzazolo[3,2-alpha]quinolinium chlorides.

Previously we reported [20] that there is no correlation between the cytotoxic activity of four new structural analogs of the antitumor DNA intercalator 3-nitrobenzothiazolo[3,2-a]quinolinium chloride (NBQ-2) and their interaction with DNA. In the present study, we present evidence suggesting that the molecular basis for the anti-proliferative activity of these drugs is the inhibition of topoisomerase II. The NBQ-2 derivatives inhibited the relaxation of supercoiled DNA plasmid pRYG mediated by purified human topoisomerase II. Inhibition of the decatenation of kinetoplast DNA mediated by partially purified topoisomerase II extracted from the human histiocytic lymphoma U937 (a cell line previously shown to be sensitive to the drugs) was also caused by these drugs. The potency of the benzazolo[3,2-a]quinolinium drugs against topoisomerase II in vitro was the following: 7-(1-propenyl)-3-nitrobenzimidazolo[3,2-a]quinolinium chloride (NBQ-59) > 4-chlorobenzothiazolo[3,2-a]quinolinium chloride (NBQ-76) > 7-ethyl-3-nitrobenzimidazolo[3,2-a]quinolinium chloride (NBQ-48) > 7-benzyl-3-nitrobenzimidazolol[3,2-a]quinolinium chloride (NBQ-38). This rank of potency for topoisomerase II inhibition correlated very well with the cytotoxicity elicited by these drugs. Furthermore, significant levels of topoisomerase II/DNA cleavage complex induced by these drugs in vivo were detected when U937 cells were treated with NBQ-59 and NBQ-76 whereas NBQ-38 and NBQ-48 produced negligible amounts of the cleavage complex. Our results strongly suggest that topoisomerase II is the major cellular target of this family of compounds.