Recreational football is medicine against non-communicable diseases: A systematic review

The purpose of this research was to conduct a systematic review of published articles related to the effect of recreational football on non-communicable diseases. A systematic review of Web of Science, SPORTDiscus, MEDLINE, and PubMed databases was performed according to PRISMA guidelines. Only empirical studies were included. There were no restrictions on the types of study design eligible for inclusion. The primary outcome measures result from the potential effects of recreational football on non-communicable diseases (eg, blood pressure, bone density, LDL cholesterol, and fat mass). A total of 44 articles met the inclusion criteria and were included. Recreational football is shown to: (a) decrease blood pressure and resting heart rate, improve cardiac structure and functioning, as well as increase maximal oxygen uptake in both sexes; (b) reduce cholesterol and triglycerides levels, increase insulin sensitivity, and have a positive impact on glycemic control; (c) improve bone mineralization, increase both bone mineral density and content, as well as acting as a stimulus for osteogenesis; and (d) be clearly beneficial for bone health, while slightly beneficial for body composition, muscle strength, and maximal oxygen uptake in adults with prostate cancer. The present systematic review demonstrated the benefits of recreational football practice on non-communicable diseases related to cardiovascular and bone health, body composition, type 2 diabetes, and prostate cancer. The effectiveness of recreational football on the aforementioned diseases may be related to age and gender; however, further research is required.     

Structural basis for cooperative interactions of substituted 2-aminopyrimidines with the acetylcholine binding protein

The nicotinic acetylcholine receptor (nAChR) and the acetylcholine binding protein (AChBP) are pentameric oligomers in which binding sites for nicotinic agonists and competitive antagonists are found at selected subunit interfaces. The nAChR spontaneously exists in multiple conformations associated with its activation and desensitization steps, and conformations are selectively stabilized by binding of agonists and antagonists. In the nAChR, agonist binding and the associated conformational changes accompanying activation and desensitization are cooperative. AChBP, which lacks the transmembrane spanning and cytoplasmic domains, serves as a homology model of the extracellular domain of the nAChRs. We identified unique cooperative binding behavior of a number of 4,6-disubstituted 2-aminopyrimidines to Lymnaea AChBP, with different molecular variants exhibiting positive, n_H > 1.0, and negative cooperativity, n_H < 1.0. Therefore, for a distinctive set of ligands, the extracellular domain of a nAChR surrogate suffices to accommodate cooperative interactions. X-ray crystal structures of AChBP complexes with examples of each allowed the identification of structural features in the ligands that confer differences in cooperative behavior. Both sets of molecules bind at the agonist-antagonist site, as expected from their competition with epibatidine. An analysis of AChBP quaternary structure shows that cooperative ligand binding is associated with a blooming or flare conformation, a structural change not observed with the classical, noncooperative, nicotinic ligands. Positively and negatively cooperative ligands exhibited unique features in the detailed binding determinants and poses of the complexes.Nicotinic acetylcholine receptors (nAChRs) function as allosteric pentamers of identical or homologous transmembrane spanning subunits. Ligand binding at two or more of the five intersubunit sites, located radially in the extracellular domain, drives a conformational change that results in the opening of a centrosymmetric transmembrane channel, internally constructed among the five subunits (SI Appendix, Fig. S2A) (1–4). Up to five potential agonist-competitive antagonist sites on the pentamer are found at the outer perimeter of the subunit interfaces. Amino acid side-chain determinants on both subunit interfaces dictate selectivity among the many subtypes of nAChRs. The interconversion between resting, active, and desensitized states occurs in the absence of ligands, and partial occupation of the binding sites suffices for agonist activation of the receptor and its antagonism (5–7). Cooperativity of agonist association and its coupling to channel gating likely play important roles in the dynamics of nicotinic responses and in sharpening the concentration and temporal windows for activation.As revealed in functional studies, most nAChRs are hetero-oligomeric, where the sites of ligand occupation are not identical (1–4). This arrangement arises when a common α-subunit pairs with one or more nonidentical subunit partners, termed non–α-subunits (7, 8). Nonidentity of the subunit interface complementary to the α-subunit may also give rise to heterogeneity in binding constants typically seen for antagonists and mask partially the degree of agonist cooperativity. An exception to this is the α7-neuronal nAChR composed of five identical subunits and exhibiting a high degree of cooperativity for agonist activation (9). Recently, sequence alignments identified genes coding for pentameric ligand-gated ion channels in prokaryotes led to the resolution of the first structure by X-ray crystallography on 3D crystals of a pentameric receptor protein from Erminia chrysanthemi (ELIC) (10) and Gloeobacter violaceus (GLIC) (11, 12) and provided high-resolution structures of the two end point states of the cooperative gating mechanism in the same pentameric ligand-gated ion channel (GLIC) (13). Recently, the first structure of a eukaryotic member of the family, the anionic glutamate receptor from Caenorhabditis elegans (GluCl), was solved at atomic resolution (14), revealing remarkable identity of 3D structure with GLIC.The acetylcholine binding protein (AChBP) was characterized from mollusks (15–17) and consists of only a homologous extracellular domain of the nAChR. Assembled as a homomeric pentamer, AChBP exhibits a similar profile of ligand selectivity toward the classical nicotinic agonists and antagonists of quaternary amine, tertiary and secondary amine (alkaloid), imine, and peptide origin that bind nicotinic receptors (18–25). If looked at solely on the basis of ligand-binding capacities, AChBP could be considered as a distinct subtype of nAChR. Although its homomeric composition and ligand selectivity best resemble the α7-subtype of nAChR, when the concentration dependence of ligand occupation has been examined, no evidence of cooperativity emerged (21). Accordingly the cooperative behavior for both activation and desensitization of receptors, seen for the classical nicotinic agonists with nAChRs, might arise from a cooperative torsional motion driven by the transmembrane spanning domain of the receptor (26).We demonstrate here a set of ligands that bind to the AChBP in a cooperative fashion, whereby binding to a single subunit affects the binding energy at identical interfaces in the pentamer. Hence, interactions within the extracellular domain of this family of homologous pentameric proteins establish a circumferential linkage between subunit interfaces which results in cooperative behavior.     

Tricho-rhino-phalangeal syndrome in a 13-year-old girl with chronic renal failure and severe growth retardation

Introduction: The tricho-rhino-phalangeal syndrome type III (TRPS III) is a rare autosomal dominantly inherited condition. The main clinical features are sparse and slow-growing hair and nails, a pear-shaped nose with a bulbous tip, elongated and flat philtrum, thin upper lip, cone-shaped epiphyses of the phalanges, and short stature. All patients have a point mutation in the TRPS1 gene. Case report: In this paper, we present a 13-year-old female with the typical clinical features of TRPS III, extreme growth retardation, severe deformities of both proximal radii resulting in limited extension of the elbows, and chronic renal failure (CRF) in addition. Molecular diagnostics revealed a missense mutation in exon 6 of TRPS1 that she inherited from her father who is also affected with TRPS III, but does not have CRF. In the index patient, the CRF was found to be due to bilateral renal hypodysplasia (RHD). Conclusion: Beside the renal dysplasia, the girl had severe deformities of the proximal radii – findings which have not been reported so far in TRPS III.     

Photodynamic antibacterial effect of graphene quantum dots

Synthesis of new antibacterial agents is becoming increasingly important in light of the emerging antibiotic resistance. In the present study we report that electrochemically produced graphene quantum dots (GQD), a new class of carbon nanoparticles, generate reactive oxygen species when photoexcited (470 nm, 1 W), and kill two strains of pathogenic bacteria, methicillin-resistant Staphylococcus aureus and Escherichia coli. Bacterial killing was demonstrated by the reduction in number of bacterial colonies in a standard plate count method, the increase in propidium iodide uptake confirming the cell membrane damage, as well as by morphological defects visualized by atomic force microscopy. The induction of oxidative stress in bacteria exposed to photoexcited GQD was confirmed by staining with a redox-sensitive fluorochrome dihydrorhodamine 123. Neither GQD nor light exposure alone were able to cause oxidative stress and reduce the viability of bacteria. Importantly, mouse spleen cells were markedly less sensitive in the same experimental conditions, thus indicating a fairly selective antibacterial photodynamic action of GQD.     

Epizootiological survey of small mammals as Leptospira spp. reservoirs in Eastern Croatia

In this survey we investigated a population of small mammals in Eastern Croatia in order to determine Leptospira carriage rates and identify circulating serovars. Out of 67 trapped animals, 20 (29.9%) isolates were obtained. Identification of isolates using microscopic agglutination test, pulsed field gel electrophoresis and multi locus sequence typing revealed that 10 (50.0%) isolates belong to serogroup Pomona, serovar Mozdok, 6 (30.0%) isolates to serogroup Australis, serovar Jalna, 2 (10.0%) isolates to serogroup Sejroe, serovar Saxkoebing, and 1 (5.0%) isolate to serogroup Grippotyphosa, serovar Grippotyphosa. One isolate from serogroup Bataviae was unable to be identified to the serovar level. Amplification of a 331-bp region of the locus LA0322 using real-time polymerase chain reaction determined that 12 (60.0%) isolates belong to L. kirschneri, 6 (30.0%) isolates to L. interrogans, and 2 (10.0%) isolates to L. borgpetersenii. Leptospira carriage rate was high (29.9%), which corresponds to a high incidence of human and domestic animal leptospirosis in Eastern Croatia. Furthermore, 90.0% of the isolates belong to serogroups Pomona, Australis and Sejroe which are also the most prevalent serogroups in humans in this area. These findings suggest that small mammals might be an important source of Leptospira spp. infection in Eastern Croatia.     

Inhibitory effects of the nucleoside analogue gemcitabine on prostatic carcinoma cells

Gemcitabine (2≺,2≺difluoro-2≺deoxycytidine, dFdC) is a synthetic antimetabolite of the cellular pyrimidine nucleotide metabolism. In a first series of in vitro experiments, the drug showed a strong effect on the proliferation and colony formation of the human androgen-sensitive tumor cell line LNCaP and the androgen-insensitive cell lines PC-3 and DU-145. Maximal inhibition occurred at a dFdC concentration as low as 30 nM. In contrast to the cell lines which were derived from metastatic lesions of prostate cancer patients, no inhibitory effects were found in normal primary prostatic epithelial cells at concentrations up to 100 nM. The effect of gemcitabine was reversed by co-administration of 10–100 μM of its natural analogue deoxycytidine. In view of a future clinical application of this anti-tumor drug in advanced prostatic carcinoma, we have compared the effect of gemcitabine on prostatic tumor cells with that on bone marrow granulopoietic-macrophagic progenitor cells, because neutropenia is a common side effect of gemcitabine treatment. The time course of action on the two kinds of cells was markedly different. Colony formation of tumor cells was inhibited by two thirds at a gemcitabine concentration of about 3.5 nM. The same effect on granulopoietic-macrophagic progenitor cells required a concentration of 9 nM. Co-administration of deoxycytidine to gemcitabine-treated tumor cell cultures completely antagonized the effect of gemcitabine whereas addition of deoxycytidine after 48 hr of gemcitabine treatment could not prevent gemcitabine action on the tumor cells. In contrast, more than half of the granulopoietic-macrophagic progenitor cells could still be rescued by deoxycytidine administration after 48 hr. These findings and the marked difference in the susceptibility of neoplastic and normal prostatic cells suggest that gemcitabine is a promising substance which should be further evaluated as to its efficacy in the treatment of advanced prostatic carcinoma. © 1996 Wiley-Liss, Inc.     

In reply to Swain et al.: Re-evaluation of updated meta-analysis including trials RTOG 1016 and De-ESCALaTE

European Archives of Oto-Rhino-Laryngology -     

Evaluation of ventricular synchrony using novel Doppler echocardiographic indices in patients with heart failure receiving cardiac resynchronization therapy.

Cardiac resynchronization therapy improves hemodynamics in selected patients with heart failure. Mechanic asynchrony parameters that may guide patient selection or therapy optimization are still being investigated. A biventricular (BiV) pacemaker was implanted in 34 patients with dilated ischemic, idiopathic, or valvular cardiomyopathy, and a QRS duration of > or =130 milliseconds. Two-dimensional standard and Doppler tissue echocardiography was performed during right ventricular (RV), left ventricular (LV), BiV, and no pacing in a random and blinded manner. LV and BiV pacing increased stroke volume (P <.02 for both) and ejection fraction (P <.001 for both). Regional contractility assessed by displacement, strain rate, and peak systolic strain was improved in some segments (P <.05) during LV and BiV pacing. A homogenization of segmental contractions was observed during LV and BiV pacing as evaluated by net systolic displacement and segmental myocardial performance index. LV and BiV pacing provides benefits that can be quantified by echocardiography.     

Atypical presentation of distal renal tubular acidosis in two siblings

Primary distal renal tubular acidosis (dRTA) is an inherited disease characterized by the inability of the distal tubule to lower urine pH <5.50 during systemic acidosis. We report two male siblings who presented with severe hyperchloremic metabolic acidosis, high urinary pH, nephrocalcinosis, growth retardation, sensorineural hearing loss, and hypokalemic paralysis. Laboratory investigations revealed proximal tubular dysfunction (low molecular weight proteinuria, generalized hyperaminoaciduria, hypophosphatemia with hyperphosphaturia, and hypouricemia with hyperuricosuria). There was significant hyperoxaluria and laboratory evidence for mild rhabdomyolysis. Under potassium and alkali therapy, proximal tubular abnormalities, muscular enzymes, and oxaluria normalized. A homozygous mutation in the ATP6V1B1 gene, which is responsible for dRTA with early hearing loss, was detected in both siblings. In conclusion, proximal tubular dysfunction and hyperoxaluria may be found in children with dRTA and are reversible under appropriate therapy.