Rhinovirus Infections among Hematopoietic Stem Cell Transplant Recipients: A Pre-Transplant Dilemma?

Respiratory viral infections (RVIs) in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients can be of concern due to the patients’ depressed immune status, but few data are available about the significance of a pre-transplant positive testing. In this retrospective observational study, we analyzed a cohort of patients that were transplanted between 1 January 2010 and 31 October 2019 in the Geneva University Hospitals with at least one RVI before or after transplantation. At least one RVI was detected in 319/533 (63.5%) transplanted patients. Rhinoviruses were most frequently identified (37%), followed by human coronaviruses (17.1%), parainfluenza viruses (13.9%), and influenza viruses (9.9%). First infection in the post-transplant period occurred at a mean time of 334 days (SD 338). Specific analysis of a subgroup of 65 patients with pre-transplant RVIs was performed. Among them, 39 (59%) patients had symptoms and 14 (21.2%) had a lower respiratory tract infection. Four patients (6.1%) (three rhinovirus and one influenza) needed an intensive care unit admission, of which, three (4.5%) (two rhinovirus and one influenza) were intubated. The patient with influenza infection diagnosed the day of the transplantation died within the first 30 days of the infection. Two patients with rhinovirus infection died within 3 months of unrelated causes. Our data show that rhinovirus infections are predominant in allo-HSCT patients, including among pre-transplant infections; however, mortality due to pre-transplant RVI is low and was only clearly identified in one patient with influenza infection. RVI within the month preceding allo-HSCT is not associated with direct morbidity or mortality in this cohort.     

HIF inhibitor 32-134D eradicates murine hepatocellular carcinoma in combination with anti-PD1 therapy

Hepatocellular carcinoma (HCC) is a major cause of cancer mortality worldwide and available therapies, including immunotherapies, are ineffective for many patients. HCC is characterized by intratumoral hypoxia, and increased expression of hypoxia-inducible factor 1α (HIF-1α) in diagnostic biopsies is associated with patient mortality. Here we report the development of 32-134D, a low-molecular-weight compound that effectively inhibits gene expression mediated by HIF-1 and HIF-2 in HCC cells, and blocks human and mouse HCC tumor growth. In immunocompetent mice bearing Hepa1-6 HCC tumors, addition of 32-134D to anti-PD1 therapy increased the rate of tumor eradication from 25% to 67%. Treated mice showed no changes in appearance, behavior, body weight, hemoglobin, or hematocrit. Compound 32-134D altered the expression of a large battery of genes encoding proteins that mediate angiogenesis, glycolytic metabolism, and responses to innate and adaptive immunity. This altered gene expression led to significant changes in the tumor immune microenvironment, including a decreased percentage of tumor-associated macrophages and myeloid-derived suppressor cells, which mediate immune evasion, and an increased percentage of CD8⁺ T cells and natural killer cells, which mediate antitumor immunity. Taken together, these preclinical findings suggest that combining 32-134D with immune checkpoint blockade may represent a breakthrough therapy for HCC.     

Calcium consumption and insulin resistance syndrome parameters. Data from the Epidemiological Study on the Insulin Resistance Syndrome (DESIR)

Background and aimA number of studies have investigated the role of dietary calcium in lipid metabolism and weight regulation, and the influence of dairy products on the incidence of insulin resistance syndrome. In this study we have examined the relationship between dietary calcium and the established parameters of the insulin resistance syndrome.Methods and resultsThe study population (n = 4372) was taken from the DESIR (Data from the Epidemiological Study on the Insulin Resistance Syndrome) cohort. Data for parameters relating to the syndrome were recorded, including glucose, serum insulin, triglycerides, HDL-cholesterol, waist circumference and blood pressure. Total energy, calcium and alcohol intake were estimated using a food-frequency questionnaire. Relationships between dietary calcium density and the above parameters were analyzed by multiple linear regression models, adjusted for age, smoking, alcohol consumption and physical activity. From one quartile of calcium density to the next, mean systolic and diastolic blood pressures and insulin concentrations decreased in women by 0.9 mmHg, 0.5 mmHg and 2.4%, respectively, and HDL-cholesterol increased by 0.007 mmol/l (all p < 0.05) after adjustment for age, smoking, alcohol intake and physical activity. In men, there was an increase of 0.2 kg/m² in the body mass index(BMI) and a decrease of 0.4 mmHg in diastolic blood pressure (both p < 0.05).ConclusionsThese results confirm a beneficial association between dietary calcium and arterial blood pressure, insulin and HDL-cholesterol levels in women, whereas in men there was only a beneficial association with diastolic blood pressure.     

Familial isolated pituitary adenomas experience at a single center: clinical importance of AIP mutation screening

We present four FIPA kindred discussing clinical and molecular data and emphasizing the differences regarding AIP status, as well as the importance of genetic screening. Family 1 consists of five patients harboring somatotropinomas with germline E24X mutation in AIP. In one of the patients, acromegaly was diagnosed through active screening, being cured by surgery. Families 2 and 3 are composed of two patients with non-functioning pituitary adenomas. Family 4 comprises patients harboring a prolactinoma and a somatotropinoma. No mutations in AIP were found in these families. No patient in Family 1 was controlled with octreotide treatment, while the acromegalic patient in Family 4 was controlled with octreotide LAR. In conclusion, FIPA is a heterogeneous condition, which may be associated with AIP mutation. Genomic and clinical screening is recommended in families with two or more members harboring pituitary adenomas, allowing early diagnosis and better outcome.     

Effects of Ultracavitation and Radiofrequency on Abdominal Adiposity

Background The mechanism of fat reduction from radiofrequency occurs via the thermal stimulation of adipocyte metabolism, causing a lipase-mediated triglyceride enzyme degradation, apoptosis, and adipocyte rupture. Ultracavitation promotes fat reduction using adipose cell destruction through mechanical stimulus. The literature on the combination of these two physical agents, named ultrafrequency, is still scarce and requires consistent analysis of the effects of this therapy combination.ObjectiveThe objective of this study was to investigate the effects of radiofrequency associated with ultracavitation in the treatment of abdominal subcutaneous tissue of women.MethodsThis was a prospective, randomized clinical trial in which 45 participants were divided into three distinct groups: the control group (no treatment); ultracavitation group; and ultracavitation and radiofrequency (UCV+RF) group, each with 15 volunteers. The following variables were evaluated: weight, perimetry, plicometry, ultrasonography, treatment reactions, and patient satisfaction.ResultsThe participants in the UCV+RF group presented a more significant decrease in adipose tissue, which was verified through all the evaluation methods.ConclusionBased on our results, the simultaneous application of ultracavitation and radiofrequency generated a reduction in localized adiposity superior to the isolated use of ultracavitation.     

Association Between Polymorphisms in GRIK2 Gene and Obsessive‐Compulsive Disorder: A Family‐Based Study

Several studies support a genetic influence on obsessive‐compulsive disorder (OCD) etiology. The role of glutamate as an important neurotransmitter affecting OCD pathophysiology has been supported by neuroimaging, animal model, medication, and initial candidate gene studies. Genes involved in glutamatergic pathways, such as the glutamate receptor, ionotropic, kainate 2 (GRIK2), have been associated with OCD in previous studies. This study examines GRIK2 as a candidate gene for OCD susceptibility in a family‐based approach. Probands had full DSM‐IV diagnostic criteria for OCD. Forty‐seven OCD probands and their parents were recruited from tertiary care OCD specialty clinics from France and USA. Genotypes of single nucleotide polymorphism (SNP) markers and related haplotypes were analyzed using Haploview and FBAT software. The polymorphism at rs1556995 (P= 0.0027; permuted P‐value = 0.03) was significantly associated with the presence of OCD. Also, the two marker haplotype rs1556995/rs1417182, was significantly associated with OCD (P= 0.0019, permuted P‐value = 0.01). This study supports previously reported findings of association between proximal GRIK2 SNPs and OCD in a comprehensive evaluation of the gene. Further study with independent samples and larger sample sizes is required.     

Chitosan microencapsulation of the dispersed phase of an O/W nanoemulsion to hydrochlorothiazide delivery

In view of biopharmaceutical limitations of hydrochlorothiazide (HCTZ), Trojan-type mucoadhesive systems were proposed, aiming to improve HCTZ pharmacological properties by modulating its release. Nanoemulsions were formed spontaneously by combining medium-chain triglycerides (Lipoid^® S75 and Pluronic^® F68) and high encapsulation efficiency was obtained. The mucoadhesive properties were provided by chitosan and microencapsulation of nanoemulsions in spray-dryer was successfully achieved by using Aerosil^® as wall material. The rapid redispersion of nanoemulsion in simulated fluids led to a fast and complete release of HCTZ in gastric medium. The pharmacodynamics of HCTZ was improved, extending the diuretic activity. Once a simple and low-energy method contributed to obtain stable mucoadhesive nanoemulsions, advantages in terms of production could also be achieved, allowing easy scaling up. This novel mucoadhesive Trojan particulate system of HCTZ showed to be a promising approach to overcome limitations in terms of absorption and consequently improve the therapeutic efficacy.     

Evaluation of a protocol for rapid diagnosis of enterovirus associated with acute flaccid paralysis cases

BackgroundThe virological surveillance of acute flaccid paralysis (AFP) is a critical component of the initiative of the World Health Organization (WHO) to eradicate poliomyelitis worldwide. Furthermore rapid methods are needed either to detect or rule out the presence of polioviruses during the late stages of eradication, especially in polio-free areas.ObjectivesThe aim of this study was to evaluate a fast protocol combining one passage (5 days) in cell culture followed by RT-PCR and molecular typing in order to detect and type poliovirus (PV) and other enteroviruses associated with AFP cases.Study designA total of 216 fecal suspensions from AFP suspected cases were tested by using this approach and compared with the WHO gold standard.ResultsUsing the WHO protocol enterovirus was detected in 12 out of the 216 AFP samples (5.55%) while with the proposed protocol enterovirus was detected in 15 out of the 216 AFP samples (6.94%). The additional positive samples detected by the proposed method were classified as non-polio enteroviruses (NPEV).ConclusionsThe proposed protocol showed higher sensitivity than the WHO gold standard, reducing the entire process of identification and typing of the isolates from the typically 14–21 days to only ～6–8 days.     

Oral distribution of Candida species and presence of oral lesions in Brazilian leprosy patients under multidrug therapy

Objective:  The aim of this study was to evaluate the prevalence of Candida spp. and presence of oral lesions in Brazilian leprosy patients under multidrug therapy (MDT).
Methods:  Thirty-eight individuals (18 males and 20 females, median age 53 years) clinically and microbiologically diagnosed as leprosy (lepromatous variant), and under MDT for at least 45 days were studied. The control group constituted by 38 healthy individuals (median age 53.5), matched to the test group in relation to age, gender and oral conditions. Oral rinses were collected and the Candida identification was performed by phenotypic tests. The existence of Candida dubliniensis among the isolates was analyzed using a validated multiplex PCR assay. Twenty-nine leprosy patients were examined intra-orally for the presence of lesions. Data were analyzed by z- and Mann–Whitney tests (α = 5%).
Results:  Yeast carriage rate between leprosy patients (65.8%) and controls (47.4%) was similar ( P  = 0.099), and no significant difference between yeast counts was observed ( P  = 0.1004). Candida albicans was the most frequently isolated species in both groups. In the leprosy group, Candida tropicalis and Candida parapsilosis were also identified. In the control group, we additionally identified Candida tropicalis , Candida glabrata and Candida kefyr. Candida dubliniensis was not detected. No leprosy-related oral lesion was registered.
Conclusion:  Within the limits of the study, we concluded that Brazilian leprosy patients under MDT showed similar levels of carriage and Candida species distribution in relation to the controls.