Do Soluble Phosphates Direct the Formose Reaction towards Pentose Sugars?

The formose reaction has been a leading hypothesis for the prebiotic synthesis of sugars such as ribose for many decades but tends to produce complex mixtures of sugars and often tars. Channeling the formose reaction towards the synthesis of biologically useful sugars such as ribose has been a holy grail of origins-of-life research. Here, we tested the hypothesis that a simple, prebiotically plausible phosphorylating agent, acetyl phosphate, could direct the formose reaction towards ribose through phosphorylation of intermediates in a manner resembling gluconeogenesis and the pentose phosphate pathway. We did indeed find that addition of acetyl phosphate to a developing formose reaction stabilized pentoses, including ribose, such that after 5 h of reaction about 10-fold more ribose remained compared with control runs. But mechanistic analyses using liquid chromatography-mass spectrometry showed that, far from being directed towards ribose by phosphorylation, the formose reaction was halted by the precipitation of Ca2+ ions as phosphate minerals such as apatite and hydroxyapatite. Adding orthophosphate had the same effect. Phosphorylated sugars were only detected below the limit of quantification when adding acetyl phosphate. Nonetheless, our findings are not strictly negative. The sensitivity of the formose reaction to geochemically reasonable conditions, combined with the apparent stability of ribose under these conditions, serves as a valuable constraint on possible pathways of sugar synthesis at the origin of life.

Macroalgal forest vs sea urchin barren: Patterns of macro-zoobenthic diversity in a large-scale Mediterranean study.

The study aimed at contributing to the knowledge of alternative stable states by evaluating the differences of mobile and sessile macro-zoobenthic assemblages between sea urchin barrens and macroalgal forests in coastal Mediterranean systems considering a large spatial scale. Six sites (100 s km apart) were selected: Croatia, Montenegro, Sicily (Italy), Sardinia (Italy), Tuscany (Italy), and Balearic Islands (Spain). A total of 531 taxa, 404 mobile and 127 sessile macro-invertebrates were recorded. Overall, 496 and 201 taxa were found in macroalgal forests and in barrens, respectively. The results of this large-scale descriptive study have met the expectation of lower macrofauna complexity and diversity in barrens rather than in macroalgal forests, and have allowed estimating the differences in levels of diversity and the consistency of variability across Mediterranean sites. Some peculiar patterns in barrens, related to both abundance of specific taxa and to high values of beta diversity, have been evidenced.

Spa therapy induces clinical improvement and protein changes in patients with chronic back pain.

This study is primarily aimed at assessing serum changes on a large panel of proteins in patients with chronic back pain following spa therapy, as well as evaluating different spa therapy regimens as a preliminary exploratory clinical study. Sixty-six patients with chronic back pain secondary to osteoarthritis were randomly enrolled and treated with daily mud packs and bicarbonate-alkaline mineral water baths, or a thermal hydrotherapy rehabilitation scheme, the combination of the two regimens or usual medication only (control group), for two weeks. Clinical variables were evaluated at baseline, after 2 and 12 weeks. One thousand serum proteins were tested before and after a two-week mud bath therapy. All spa treatment groups showed clinical benefit as determined by improvements in VAS pain, Roland Morris disability questionnaire and neck disability index at both time points. The following serum proteins were found greatly increased (≥2.5 fold) after spa treatment: inhibin beta A subunit (INHBA), activin A receptor type 2B (ACVR2B), angiopoietin-1 (ANGPT1), beta-2-microglobulin (B2M), growth differentiation factor 10 (GDF10), C-X-C motif chemokine ligand 5 (CXCL5), fibroblast growth factor 2 (FGF2), fibroblast growth factor 12 (FGF12), oxidized low density lipoprotein receptor 1 (OLR1), matrix metallopeptidase 13 (MMP13). Three proteins were found greatly decreased (≤0.65 fold): apolipoprotein C-III (Apoc3), interleukin 23 alpha subunit p19 (IL23A) and syndecan-1 (SDC1). Spa therapy was confirmed as beneficial for chronic back pain and proved to induce changes in proteins involved in functions such as gene expression modulation, differentiation, angiogenesis, tissue repair, acute and chronic inflammatory response.

V348I mutation in UL23 gene of human herpesvirus 1 in a case of herpetic hepatitis and haemophagocytic lymphohistiocytosis.

We herein report the case of a young immunocompetent adult patient with a rapidly fatal haemophagocytic lymphohistiocytosis syndrome related to human herpesvirus 1 (HHV-1) infection, with herpetic hepatitis and persistent high-level viraemia despite treatment with acyclovir. Haemophagocytic lymphohistiocytosis was confirmed in the patient's spleen and bone marrow. HHV-1 DNA was extracted from whole blood and liver biopsy and the UL23 gene was sequenced. A V348I natural polymorphism of the TK protein was found in blood and liver specimens. Further studies are needed to investigate the role of this polymorphism in the development of systemic immune dysregulation.

Detectable cerebrospinal fluid JCV DNA in late-presenting HIV-positive patients: beyond progressive multifocal leukoencephalopathy?

In the absence of effective prophylaxis and treatment, therapeutic options in HIV-positive patients with progressive multifocal leukoencephalopathy (PML) are limited to antiretroviral therapy: nevertheless, outcome is poor. We conducted a retrospective study (2009-2015) describing the outcome of 25 HIV-positive patients with detectable cerebrospinal fluid JC virus DNA: 14 had a probable PML while the others had evidence of other inflammatory central nervous system (CNS) affecting disorders. In the former group, 6-month mortality was 45.5% vs 21.4 in the latter one: survival was higher than previously described but no predictor of poor outcome was identified. Two patients treated with 5HT2-inhibitors survived. The contributing role of JCV replication in other CNS-affecting disorders needs to be assessed as well as the benefits of 5HT2-inhibitors in HIV-positive patients with proven PML.

Treatment with direct-acting antiviral agents of hepatitis C virus infection in injecting drug users: A prospective study.

In this prospective study, we evaluated the effectiveness and tolerability of novel therapies against hepatitis C virus (HCV) in a cohort of PWID enrolled at our centre from April 2015 to July 2016. In this analysis, a total of 174 patients were included: eleven (6.3%) were treated with pegylated interferon (PEG-IFN) and ribavirin (RBV) containing regimens, 163 (93.7%) with IFN-free treatments. RBV has been used in 70 patients (40.2%); 59 (33.9%) patients were in opioid substitution therapy (OST) with methadone or buprenorphine. Overall, sustained virological response (SVR) has been observed in 162 subject (93.1%), breakthrough (BT) in three (1.7%), relapse in one (0.6%) and dropout in eight (4.6%). Treatment was interrupted for clinical conditions in seven patients: six (3.4%) had hepatic decompensation and one died for hepatocellular carcinoma (HCC). In multivariate analysis, predictive factors of treatment failure were as follows: albumin level below 3 g/dL (OR=7.190; 95% IC=1.236-41.837; P<.001), MELD score >10 (OR=5.886; 95% IC=1.411-35.994; P<.001) and years of HCV infection >20 (OR=1.286; 95% IC=0.556-9.455; P=.016). In conclusion, treatment with DAAs was effective and well tolerated in PWID; cirrhotic subjects with MELD > 10 and albumin low level showed a higher risk of developing serious adverse events and treatment failure.

Endoparasites detected in faecal samples from dogs and cats referred for routine clinical visit in Sardinia, Italy.

This study aimed to update data on the prevalence of intestinal and lung parasitic infections in owned dogs and cats in Sardinia, Italy. Examinations on faecal samples from 619 dogs and 343 cats routinely referred to the Veterinary Teaching Hospital of the University of Sassari were performed between the years of 2011 and 2015. Individual faecal samples were analysed using the Wisconsin technique for copro-microscopic examination and the Baermann technique for the presence of lungworm larvae. Endoparasites were found in 34.9% and 43.4% of examined dogs and cats, respectively. Helminthic infections (21.2% in dogs and 32.6% in cats) occurred more frequently than protozoan infections (17.9% in dogs and 17.8% in cats). In both dogs and cats, the most common parasites were ascarids (12.1% and 15.7%), Cystoisospora spp. (10.2% and 10.8%), Giardia duodenalis (9.4% and 8.5%), and hookworms (7.9% and 5.5%). Evidence of bronchopulmonary nematode infections were found in 0.8% of examined dogs and in 15.8% of examined cats. Age was identified as a risk factor, with animals younger than 6months more frequently infected than older animals, while no significant association was observed for gender. This study demonstrated that endoparasites in owned dogs and cats of Sardinia have considerably high prevalence. Veterinary practitioners and pet owners should be more aware of these infections and should adopt more effective and standardized control practices.

The trochanter tertius in a dog.

The tuberositas glutaea is a rudimentary structure in the dog's os femoris. It gives attachment to the superficial gluteal muscle, and is known by veterinary anatomists and orthopedic surgeons as trochanter tertius. We report an atypical eminence exposed through a surgical approach on a Cane Corso Dog. Anatomic and radiographic investigations led us to recognize this eminence as an abnormally grown tuberositas glutaea.

Avulsion of the greater trochanter and craniodorsal luxation of the hip joint in a cat: importance of precise radiographic evaluation.

A traumatic coxofemoral luxation was diagnosed in a 15-month-old European neutered male cat, and on the basis of the radiographic evaluation a closed reduction was performed. Consequently, the cat was presented at the University of Bologna because of the failure of the treatment. A supplementary radiographic exam revealed the concomitant avulsion of the greater trochanter, consequently surgical management of the coxofemoral luxation was attempted successfully. Therefore, correct planning of the radiographic examination should be considered to prevent possible mistakes.

Combined intra-extra-articular technique for stabilisation of coxofemoral luxation. Preliminary results in two dogs.

OBJECTIVE: To report a new technique for repairing traumatic cranio-dorsal coxofemoral luxation in dogs. METHODS: Stabilisation of hip luxation was carried out in two dogs: a one-year-old male Border Collie and an eight-year-old female American Staffordshire Bull Terrier. A caudal approach was performed to expose the hip joint. Following this, a 2.5 mm hole was drilled through the acetabular wall at the original attachment of the round ligament, followed by a tunnel between the fovea capitis and the proximal third of the femur. Nylon tape was tied in a clove hitch knot around the femoral neck. The tape was placed as a bridge over the ischial spine to create an acetabular roof in order to increase articular stabilisation. RESULTS: Follow-up examinations were performed at 10, 40 and 90 days after surgery.The dogs did not show any signs of lameness, pain or reoccurrence of the luxation during any of the follow-up examinations. CLINICAL SIGNIFICANCE: This tape-technique enabled reinforcement of the acetabular roof which in turn increased the stability of the joint.

Rotation of the femoral trochlea for treatment of medial patellar luxation in a dog.

A crossbreed dog was presented with non-weight bearing on the right hindlimb and a semi-flexed stifle. Clinical examination and radiographic investigation showed a grade 3 medial patellar luxation, characterised by hypoplasia of the medial trochlear ridge. No other significant skeletal abnormalities were detected. A 180 degrees rotation of the femoral trochlea was the surgical technique chosen to treat the trochlear dysplasia, the aim being to move the normal lateral ridge to the medial side and thereby prevent patellar luxation. This technique was able to restore correct conformation of the femoral trochlea and preserve the integrity of the trochlear groove cartilage, thus potentially retarding the progression of degenerative joint disease. The dog recovered fully and postoperative radiographic examinations showed healing of the rotated trochlea with only mild signs of degenerative joint disease.

The performance of poly-epsilon-caprolactone scaffolds in a rabbit femur model with and without autologous stromal cells and BMP4.

The ability of a cellular construct to guide and promote tissue repair strongly relies on three components, namely, cell, scaffold and growth factors. We aimed to investigate the osteopromotive properties of cellular constructs composed of poly-epsilon-caprolactone (PCL) and rabbit bone marrow stromal cells (BMSCs), or BMSCs engineered to express bone morphogenetic protein 4 (BMP4). Highly porous biodegradable PCL scaffolds were obtained via phase inversion/salt leaching technique. BMSCs and transfected BMSCs were seeded within the scaffolds by using an alternate flow perfusion system and implanted into non-critical size defects in New Zealand rabbit femurs. In vivo biocompatibility, osteogenic and angiogenic effects induced by the presence of scaffolds were assessed by histology and histomorphometry of the femurs, retrieved 4 and 8 weeks after surgery. PCL without cells showed scarce bone formation at the scaffold-bone interface (29% bone/implant contact and 62% fibrous tissue/implant contact) and scarce PCL resorption (16%). Conversely, PCL seeded with autologous BMSCs stimulated new tissue formation into the macropores of the implant (20%) and neo-tissue vascularization. Finally, the BMP4-expressing BMSCs strongly favoured osteoinductivity of cellular constructs, as demonstrated by a more extensive bone/scaffold contact.

A simplified technique for diagnostic and surgical arthroscopy of the shoulder joint in the dog.

A modified technique is presented for surgical and diagnostic arthroscopy of the shoulder joint in the dog. The technique involves access to the joint through two points only; one was created in place of the drainage needle-cannula, which was replaced with a portal, while the second was located more caudally compared with previous techniques. Using a changing guide rod system the two portals are completely interchangeable in order to perform easier arthroscopic surgery either in the cranial or caudal aspect of the joint. The presence of only one portal caudal to the lateral collateral ligament allows more freedom of movement and avoids interference between the arthroscope and the instruments. The modified procedure was performed on 33 joints affected by osteochondritis dissecans or tenoligament diseases and facilitated straightforward diagnostic examinations, and simple and rapid surgical procedures.

Effects of sildenafil on esophageal motility of normal subjects.

Sildenafil shows an intense and prolonged inhibitory effect on the smooth muscle cells of corpus cavernosum arterioles by blocking phosphodiesterase type 5 that inactivates the nitric oxide-stimulated cyclic guanosine monophosphate. We investigated if this inhibitory effect is also displayed on smooth muscle cells of the esophagus. In 16 normal subjects (9 men and 7 women, mean age 34 years, range 22-56) esophageal motility was recorded by means of a low-compliance manometric system with side holes for the esophageal body and a sleeve for the lower esophageal sphincter (LES). After a basal period of 60 min, a tablet of sildenafil 50-mg ground and dissolved in water was infused in the stomach in eight subjects (group A) and a placebo tablet in the other eight subjects (group B), randomly and in a double-blind manner; the recording continued for another 60 min. LES tone and postdeglutitive residual pressure, as well as amplitude, propagation velocity, and onset latency of contractions were measured each minute, the values averaged every 5 min, and the mean of the entire basal and postinfusion periods was calculated. The postinfusion values were compared with the basal values in each group and with the corresponding values of the other groups. The percent variations of postinfusion values with respect to basal values were also compared. Sildenafil induced a statistically significant decrease of LES tone, residual pressure, wave amplitude, and propagation velocity and a significant increase of onset latency of pressure waves in comparison with the values of the basal period and placebo. The inhibitory effect reached its maximum 10-15 min after the infusion and lasted about 1 hr. In conclusion, sildenafil markedly inhibits the motor activity of the esophageal musculature by decreasing LES pressure, wave amplitude, and propagation velocity and increasing the onset latency of pressure waves.

[Postoperative infections: the use of thymostimulin (TP1) in patients at risk]. / Le infezioni post-operatorie: l'uso della timostimolina (TP1) nei pazienti a rischio.

The authors report data related to 212 surgical patients at risk because immunocompromised. Patients were divided in two homogeneous groups, one treated with Thymostimulin and the other as a control group, all affected by severe pathologies. Patients presenting postoperative complications directly related to technical reasons were excluded. Morbidity, postoperative hospitalization and mortality were the parameters considered. Positive results were obtained in the treated group compared to controls. Therefore, it is Authors' opinion that the treatment with Thymostimulin in immunocompromised patients is important in order to avoid or reduce postoperative infection rates.

[Angiomyolipoma of the kidney: a case of spontaneous rupture]. / L'angiomiolipoma del rene: un caso di rottura spontanea.

After reporting the general features of renal angiomyolipoma (AML), either isolated or associated to other conditions (Bourneville sclerosis, Wunderlich's syndrome), the Authors discuss a case complicated by perirenal spontaneous hematoma, undergone emergency operation (simple nephrectomy). At a 3 year follow-up the patient is in good general and local conditions (negative TC, normal renal function, preexistent hypertension disappeared). Literature is reviewed and some considerations about diagnosis and surgical tactics are reported.