Management of chronic testicular pain due to thoracolumbar junction syndrome: A pilot study.

INTRODUCTION: Thoracolumbar dysfunction (TLD) had been evoked as a possible etiology of chronic testicular pain. Our study investigated the efficacy of osteopathic diagnosis and treatment of TLD in men with chronic testicular pain. METHODS: Patients suffering from testicular pain were examined for thoracolumbar dysfunction and enrolled in a prospective trial if they have both conditions. Following standardized examination, all patients were prescribed 1 to 3 osteopathic treatment sessions, usually at weekly interval. Treatment success was evaluated using the Visual Analog scale and durability was assessed by regular follow-up. Patient satisfaction was also assessed. Comparison of pain improvement was done using Wilcoxon matched-pairs signed-ranks test. Logistic regression was used to assess for risk factors of success. A P<0.001 was used for significance. RESULT: Out of 62 patients enrolled, 41 patients (median age 32 years, IQR 24-37) were suffering from chronic testicular pain and TLD. 37 of the 41 participants completed the treatment and follow-up according to the plan. Patients underwent a median of 2 osteopathic treatment sessions (range 1-3). Overall, pain disappeared completely in 25 patients (67.5%) and improvement was noted in 7 patients (18.9%). After initial improvement, two patients experienced relapse at their last visit (5.4%). Five patients (13.5%) had no improvement of their symptoms after osteopathic treatment. Statistically, improvement was significant with a P<0.001 and on logistic regression, site of pain and duration of pain were the sole predictors of failure. CONCLUSION: TLD is a pathology that should be considered in the differential diagnosis in patients with chronic testicular pain and osteopathic manipulation of the spine appears to be an effective treatment option.

Simultaneous Electrochemical Detection of Dopamine and Uric Acid via Au@Cu-Metal Organic Framework.

The incorporation of noble metals with metal-organic frameworks (MOFs) are conducive to the simultaneous electrochemical detection of analytes owing to multiple accessible reaction sites. Herein, Au@Cu-metal organic framework (Au@Cu-MOF) is successfully synthesized and modified as a screen-printed carbon electrode (SPCE), which serves as an excellent electrocatalyst for the oxidation of dopamine (DA) and uric acid (UA). The sensor shows a linear range from 10 µM to 1000 µM, with sensitivity and detection limit of 0.231 µA µM-1 cm-2 and 3.40 µM for DA, and 0.275 µA µM-1 cm-2 and 10.36 µM for UA. Au@Cu-MOF could realize the individual and simultaneous electrochemical sensing of DA and UA, with distinguishable oxidation peak potentials. Moreover, it exhibits reproducibility, repeatability, and stability. Ultimately, the sensor provides an avenue for an ultrasensitive label-free electrochemical detection of DA and UA.

Acute Fever of Unknown Origin: A Presentation of West Nile Encephalitis.

INTRODUCTION: West Nile virus is an asymptomatic infection in most cases, but it can present with a rare complication of deadly neuroinvasive disease. CASE PRESENTATION: A 81-year-old White man presented with altered mental status and fever of unknown origin. After extensive workup, he was diagnosed with West Nile encephalitis based on positive serology, lumbar puncture, and clinical presentation. DISCUSSION: West Nile virus is a mosquito-borne RNA arbovirus that, in rare cases, can lead to encephalitis, which is a challenging diagnosis. There is no current treatment; however, a 5-day course of intravenous immunoglobulin seemed to show acute clinical improvement in both mentation and magnetic resonance imaging of the head and no long-term effects. CONCLUSION: We report this case to increase awareness among clinicians to include West Nile virus in the differential diagnosis of encephalitis with fever of unknown origin, particularly in endemic areas.

Betaine supplementation to rats alleviates disturbances induced by high-fat diet: pleiotropic effects in model of type 2 diabetes.

Betaine is a biologically active compound exerting beneficial effects in the organism, however, the exact mechanisms underlying its action are not fully elucidated. The present study aimed to explore, whether betaine alleviates disorders induced by feeding rats a high-fat diet (HFD). Rats were divided into 3 groups: control, fed an HFD and fed an HFD and receiving betaine (2% water solution for 8 weeks). Betaine improved glucose tolerance, decreased blood levels of non-esterified fatty acids and prevented lipid accumulation in the skeletal muscle of rats on an HFD. Betaine reduced activities of blood alanine aminotransferase, blood levels of bilirubin and hepatic lipid content. Expression of fatty acid synthase in the liver and the skeletal muscle was decreased in response to feeding an HFD, and this effect was deepened by betaine in the muscle tissue. Hepatic and muscular expression of genes related to insulin signaling were unchanged in HFD-fed rats. Lipolysis stimulated by epinephrine (an adrenergic receptor agonist), forskolin (an activator of adenylate cyclase), dibutyryl-cAMP (an activator of protein kinase A) and DPCPX (an adenosine A1 receptor antagonist) was diminished in the adipocytes of rats fed an HFD, however, this effect was alleviated by betaine. Moreover, blood leptin levels in HFD-fed rats were elevated, whereas leptinemia have normalized by betaine supplementation. Betaine prevented the increase in expression of N-methyl D-aspartate receptors in the hippocampus and in the cerebral cortex. These results indicate that betaine positively affects the insulin-sensitive tissues: liver (hepatoprotective effects), skeletal muscle (reduced lipid accumulation) and adipose tissue (a rise in lipolysis), which is associated with improved insulin sensitivity. Betaine-induced prevention of hyperleptinemia indicates restoration of leptin action, and changes in the brain reveal neuroprotective properties. Our results show that betaine induces positive changes in HFD-fed rats, its action is pleiotropic and involves different tissues.

VerSe: A Vertebrae labelling and segmentation benchmark for multi-detector CT images.

Vertebral labelling and segmentation are two fundamental tasks in an automated spine processing pipeline. Reliable and accurate processing of spine images is expected to benefit clinical decision support systems for diagnosis, surgery planning, and population-based analysis of spine and bone health. However, designing automated algorithms for spine processing is challenging predominantly due to considerable variations in anatomy and acquisition protocols and due to a severe shortage of publicly available data. Addressing these limitations, the Large Scale Vertebrae Segmentation Challenge (VerSe) was organised in conjunction with the International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI) in 2019 and 2020, with a call for algorithms tackling the labelling and segmentation of vertebrae. Two datasets containing a total of 374 multi-detector CT scans from 355 patients were prepared and 4505 vertebrae have individually been annotated at voxel level by a human-machine hybrid algorithm (https://osf.io/nqjyw/, https://osf.io/t98fz/). A total of 25 algorithms were benchmarked on these datasets. In this work, we present the results of this evaluation and further investigate the performance variation at the vertebra level, scan level, and different fields of view. We also evaluate the generalisability of the approaches to an implicit domain shift in data by evaluating the top-performing algorithms of one challenge iteration on data from the other iteration. The principal takeaway from VerSe: the performance of an algorithm in labelling and segmenting a spine scan hinges on its ability to correctly identify vertebrae in cases of rare anatomical variations. The VerSe content and code can be accessed at: https://github.com/anjany/verse.

A new pharmacokinetic model for 90Y-ibritumomab tiuxetan based on 3-dimensional dosimetry.

Monoclonal antibodies (mAbs) are key components in several therapies for cancer and inflammatory diseases but current knowledge of their clinical pharmacokinetics and distribution in human tissues remains incomplete. Consequently, optimal dosing and scheduling in clinics are affected. With sequential radiolabeled mAb-based imaging, radiation dosing in tissues/organs can be calculated to provide a better assessment of mAb concentrations in tissues. This is the first pharmacokinetic model of 90Y-Ibritumomab tiuxetan (90Y-IT) in humans to be described, based on three-dimensional (3D) dosimetry using single-photon emission computed-tomography coupled with computed-tomography. 19 patients with follicular lymphoma were treated initially with 90Y-IT in the FIZZ trial. Based on a compartmental approach individualising the vascular compartment within studied organs, this study proposes a reliable pharmacokinetic (PK) five-compartment model replacing the currently used two-compartment model and constitutes a new direction for further research. This model provides exchange constants between the different tissues, Area Under the Curve of 111In-IT in blood (AUC) and Mean Residence Time (MRT) that have not been reported so far for IT. Finally, the elimination process appears to occur in a compartment other than the liver or the spleen and suggests the metabolism of mAbs may take place mainly on the vascular compartment level.

[Etology and treatment of community acquired pneumonia in children]. / Pneumonies communautaires chez l'enfant: étiologie et traitement.

In children under 5 years, most lower respiratory tract infections are caused by viruses and do not require antibiotics. This is true for almost all episodes of bronchitis and bronchiolitis but also for the majority of pneumonias. Atypical pneumonias due to Mycoplasma pneumoniae or Chlamydia pneumoniae predominate in older children while Streptococcus pneumoniae remains by far the most common cause of bacterial pneumonia. Diagnosis of pneumonia itself can be difficult and relies on a combination of clinical judgement and radiological and laboratory investigations. In real-life situations, etiologic agents are rarely identified, an issue further complicated by the possibility of mixed infections particularly in hospitalised children. Since viruses are often the sole cause of pneumonia in childhood, it is appropriate not to treat every child with antibiotics. However, when a bacterial origin can not be excluded, antibiotics efficient on Streptococcus pneumoniae are to be prescribed. Amoxicillin is the first choice empirical antibiotic treatment, having a higher efficacy on poorly sensitive pneumococcus than cephalosporins. Macrolides are indicated for the treatment of atypical pneumonia. Current immunisation strategies have decreased the number of bacterial pneumonias. However, there is some evidence that among hospitalised children the rate of complicated pneumonias is increasing with an emerging role of Streptococcus pneumoniae serotype 1, which is not covered in the 7-valent vaccine.

Pharmacogenomics and chemical library screens reveal a novel SCFSKP2 inhibitor that overcomes Bortezomib resistance in multiple myeloma.

While clinical benefit of the proteasome inhibitor (PI) bortezomib (BTZ) for multiple myeloma (MM) patients remains unchallenged, dose-limiting toxicities and drug resistance limit the long-term utility. The E3 ubiquitin ligase Skp1-Cullin-1-Skp2 (SCFSkp2) promotes proteasomal degradation of the cell cycle inhibitor p27 to enhance tumor growth. Increased SKP2 expression and reduced p27 levels are frequent in human cancers and are associated with therapeutic resistance. SCFSkp2 activity is increased by the Cullin-1-binding protein Commd1 and the Skp2-binding protein Cks1B. Here we observed higher CUL1, COMMD1 and SKP2 mRNA levels in CD138+ cells isolated from BTZ-resistant MM patients. Higher CUL1, COMMD1, SKP2 and CKS1B mRNA levels in patient CD138+ cells correlated with decreased progression-free and overall survival. Genetic knockdown of CUL1, COMMD1 or SKP2 disrupted the SCFSkp2 complex, stabilized p27 and increased the number of annexin-V-positive cells after BTZ treatment. Chemical library screens identified a novel compound, designated DT204, that reduced Skp2 binding to Cullin-1 and Commd1, and synergistically enhanced BTZ-induced apoptosis. DT204 co-treatment with BTZ overcame drug resistance and reduced the in vivo growth of myeloma tumors in murine models with survival benefit. Taken together, the results provide proof of concept for rationally designed drug combinations that incorporate SCFSkp2 inhibitors to treat BTZ resistant disease.

Pharmacologic screens reveal metformin that suppresses GRP78-dependent autophagy to enhance the anti-myeloma effect of bortezomib.

Although the therapeutic benefit of proteasome inhibition in multiple myeloma remains unchallenged, drug resistance inevitably emerges through mechanisms that remain elusive. Bortezomib provokes unwanted protein accumulation and the endoplasmic reticulum stress to activate the unfolded protein response (UPR) and autophagy as compensatory mechanisms that restore protein homeostasis. High-throughput screens to detect pharmacologics that modulated autophagy to enhance the anti-myeloma effect of bortezomib revealed metformin, a widely used antidiabetic agent with proven efficacy and limited adverse effects. Metformin co-treatment with bortezomib suppressed induction of the critical UPR effector glucose-regulated protein 78 (GRP78) to impair autophagosome formation and enhance apoptosis. Gene expression profiling of newly diagnosed myeloma patient tumors further correlated the hyperexpression of GRP78-encoding HSPA5 with reduced clinical response to bortezomib. The effect of bortezomib was enhanced with metformin co-treatment using myeloma patient tumor cells and the chemoresistant, stem cell-like side population that may contribute to disease recurrence. The relevance of the findings was confirmed in vivo as shown by metformin co-treatment with bortezomib that delayed the growth of myeloma xenotransplants. Taken together, our results suggest that metformin suppresses GRP78, a key driver of bortezomib-induced autophagy, and support the pharmacologic repositioning of metformin to enhance the anti-myeloma benefit of bortezomib.

Presence of Angiostrongylus costaricensis Morera and Céspedes 1971 in Colombia.

Angiostrongylus costaricensis, producing abdominal angiostrongyliasis, is known to occur in humans and/or rodents in the Western Hemisphere, namely in the U.S.A. (Texas), Mexico, Honduras, El Salvador, Costa Rica, Panama, Venezuela, and Brazil, Rats, Oryzomys caliginosus, in Colombia were found to harbor the parasite. First-stage larvae from one of these rats developed to third-stage larvae in the slug Veronicella occidentalis, also from Colombia.

Dermatitis caused by cercariae of Orientobilharzia turkestanicum in the Caspian Sea area of Iran.

Cercarial dermatitis is very common among rice farmers in the Caspian Sea area of Iran. The characteristic eggs of Orientobilharzia turkestanicum were found in the feces of a plowing bull. Fifty-six percent of uninfected Lymnaea gedrosiana maintained at 24-25 degrees C produced cercariae, identical to those from natural infections, 21 days after exposure to the miracidia obtained from the feces of the bull. Cercariae of O. turkestanicum from naturally infected L. gedrosiana produced dermatitis on the arm of one of us.

Unisexual infections with Schistosoma haematobium in the white mouse.

In unisexual infections with an Iranian strain of Schistosoma haematobium in white mice, female worms matured normally and deposited eggs in the liver but these eggs did not contain miracidia. Both female and male worms grew to more than half the length of corresponding mated worms in bisexual infections, and males acquired the normal number of testes.

Human schistosomiasis in Puerto Rico: reduced prevalence rate and absence of Biomphalaria glabrata.

A combined epidemiologic and malacologic survey of schistosomiasis in Puerto Rico was carried out in areas where previous surveys had reported the prevalence of the disease. This limited survey, with 495 persons examined, found a low prevalence (0.6%) of Schistosoma mansoni infections. The infections were restricted to three people more than 36 years of age. No infections were detected in children 16 years of age or less, and this cohort comprised 57.8% of the study group. Malacologic surveys of the four streams, 10 rivers, and eight lakes throughout the island revealed the absence of intermediate host Biomphalaria glabrata and the presence of Thiara granifera, a competitive species of B. glabrata and the predatory snail Marisa cornuarietis. We believe that the absence of B. glabrata is the primary reason for the sustained reduction in the prevalence of schistosomiasis in Puerto Rico.

Enzootic schistosomiasis in a Louisiana armadillo.

Trematode eggs compatible in characteristics with those of Heterobilharzia americana, a probable cause of human schistosomal dermatitis in the Gulf States of the U.S., were found in the cirrhotic liver and other viscera of a wild-caught armadillo in Louisiana. Although adult worms were not found, the current observation suggests a need to extend the known host range of this common schistosome parasite of carnivores and other wild animals in the South, and may have additional implications in the context of the public health importance of the armadillo.

Human schistosomiasis in Cameroon. II. Distribution of the snail hosts.

A nationwide survey for snail hosts of human schistosomes was carried out in Cameroon between 1985 and 1988. In total, 668 sites at 432 locations were sampled. In the arid, northern half of the country (tropical climatic zone), where both intestinal and urinary schistosomiasis are hyperendemic, Biomphalaria pfeifferi was the only Schistosoma mansoni host and Bulinus globusus and B. senegalensis the most common S. haematobium hosts. In that region, these snails occurred almost exclusively in temporary bodies of water. Taking into account results from a companion study on the distribution of schistosomiasis in humans, our results clearly show that temporary water bodies in the tropical zone are the principal foci of transmission. These findings disagree with commonly held views about schistosome transmission in Cameroon. B. truncatus, a S. haematobium host, was also present in the tropical zone but was found principally in perennial habitats. Although some perennial habitats were important transmission sites, they represent only a small portion of the overall problem. B. truncatus is the principal S. haematobium host in the wetter southern half of the country where schistosomiasis haematobium is highly focal. Biom. camerunensis was far more common than Biom. pfeifferi in the South but did not occur where S. mansoni prevalence rates were high; thus it appears to be a poor host. B. forskalii, the sole host of S. intercalatum in Cameroon, occurs widely throughout the country; however, the schistosome is restricted to a small region in the South.

Assessment of schistosomiasis in the Dominican Republic.

Active transmission of intestinal schistosomiasis is currently limited to the southeastern part of the Dominican Republic. A population-based stool survey in 1980 detected 4 asymptomatic individuals among 114 selected at random in 2 towns and a rural community in El Seibo Province. The distribution of the transmitting snail, Biomphalaria glabrata, considerably exceeds that of Schistosoma mansoni, extending to the National District and capital city of Santo Domingo and well into certain central valley provinces. There is evidence that transmission sites have shifted during the past three decades because of urban development, molluscicidal activities and, perhaps, introduction of competing mollusks. In spite of intermittent control activities, the combination of domestic and recreational use of streams with consequent fecal contamination, and the extended distribution of B. glabrata indicates that the potential for new transmission foci is as great today as it was 10 years ago. This potential transmission of S. mansoni is a continuing threat to public health in the Dominican Republic.

Suitability of six lymnaeid snails for infection with Fasciola hepatica.

The suitability of Fossaria (Bakerilymnaea) cubensis and Pseudosuccinea columella from Louisiana as intermediate hosts for Fasciola hepatica was compared to P. columella and Stagnicola elodes from Ann Arbor, MI, S. attenuata from Hidalgo, Mexico, Lymnaea gedrosiana from Iran and L. natalensis from Senegal. P. columella from LA was shown to be a more suitable host (51.3% became infected) than F. (B.) cubensis (15.2% and 26.4% of two populations became infected). The infection rate for P. columella from MI, was 50% and for L. gedrosiana was 32.5%, whereas L. natalensis, S. elodes and S. attenuata were refractory. F. (B.) cubensis and P. columella have some degree of suitability as intermediate hosts for F. hepatica under laboratory conditions, but field observations of their habitat in southern LA and characteristic management of cattle indicate that the former snail is more important as an intermediate host in this enzootic area. Tissue sections of suitable snails had few histopathological effects but physical damage caused by rediae was pronounced, mainly in the digestive gland and in the mantle.

Description of redia and cercaria of Paragonimus peruvianus from experimentally infected Aroapyrgus colombiensis of Condebamba Valley, Peru.

Although no natural infections with lung flukes were encountered in the hydrobioid snail Aroapyrgus colombiensis from streams in the Condebamba Valley, Peru, laboratory-bred snails were readily susceptible to infection with miracidia of Paragonimus peruvianus. The redia and cercaria are described for the first time for those of neotropical lung flukes. Cercariae inside rediae did not have a stylet and development was apparently completed outside the rediae in snail tissues. The microcercous xiphidiocercaria had 2 groups of gland cells on each side; the outer consisted of 5 cells and the inner of 3 cells, all with ducts opening at the stylet. The excretory bladder was large, often triangular, was thick-walled, and of 1 layer of cuboidal cells. The redia lacked procrusculi and had a short intestine which was slightly longer than the pharynx.

Aroapyrgus costaricensis, hydrobiid snail host of paragonimiasis in Costa Rica.

A small freshwater hydrobiid snail found in narrow shallow steams at various altitudes in Costa Rica is the intermediate host of Paragonimus mexicanus. Based on the morphology of its shell and soft parts the snail is assigned to the species Aroapyrgus costaricensis (Mörch). It is easily maintained in the laboratory; the female is ovoviviparous, carries up to 40 embryos in its brood pouch, and young-to-young cycle is about 10 weeks. Natural infection rates with rediae and cercariae of Paragonimus mexicanus are less than 1%, the majority of the naturally infected snails are of medium size (about 2 mm in height), but all sizes (ages) can be experimentally infected. The microcercous cercairae of P. mexicanus emerge from A. costaricensis in late afternoon and evening, about 2 months after exposure to the miracidia.

Aroapyrgus alleei Morrison, 1946 (Gastropoda: Hydrobiidae) first intermediate host of paragonimus mexicanus in Colima, Mexico.

The lung fluke Paragonimus mexicanus infects opossums in the state of Colima, on the Pacific coast of Mexico. Some of the hydrobiid snails occurring in the same area, and identified as Aroapyrgus alleei Morrison, 1946, were found naturally infected with rediae and cercariae of P. mexicanus. The morphology of A. alleei is here described and compared to that of other species of Aroapyrgus, which are actual or potential hosts of lung flukes in other enzootic or endemic areas in Central and South America.