Anterior Shoulder Dislocation with Concomitant Fracture of processus coracoideus and tuberculum majus humeri - Case Report.

Glenohumeral joint is the most frequently dislocated joint of the human body. Concomitant fractures of the coracoid process and tuberculum majus in humeral dislocation of the shoulder joint are rarely described. Concomitant fractures are results of a significant contraction of the surrounding muscles and rotator cuff during a cerebral paroxysm. Due to the small number of cases, the treatment of such injuries is not simple and it is based on an algorithm for treatment of isolated injuries of these anatomical structures. In this case report, we describe a concomitant fracture of the coracoid process and tuberculum majus during an anterior shoulder dislocation in 25-year-old patient after an epileptic seizure. The injury was treated in our department surgically, with a good functional result. The absolute Constant score for the operated arm is 95 points, the relative Constant score is 97%, DASH score 0, VAS score 0.

Site-Specific Deuteration of Polyunsaturated Alkenes.

Selective deuteration of drugs and biologically relevant molecules is becoming increasingly important in the pharmaceutical industry. Site-selective isotopic reinforcement of polyunsaturated fatty acids (PUFAs) at their bis-allylic sites has been identified as a unique approach in preventing oxidative damage in these molecules, which had been linked to neuronal and retinal diseases, atherosclerosis, and aging. Typical methods for preparation of site-selectively deuterated PUFAs require rather long, laborious, and expensive syntheses. In this report, we disclose a very efficient catalytic protocol for site-specific deuteration of PUFAs and analogous poly-alkenes under exceptional kinetic control. Deuterium oxide (D2O) has been identified not only as a deuterium source but also as a crucial component in the overall reaction mechanism responsible for averting the formation of thermodynamically favored side-products.

Prevalence and prevention of dental injuries in young taekwondo athletes in Croatia.

AIM: The aim of this study was to evaluate the occurrence of dental and facial injuries, the habit of wearing mouthguard and the awareness regarding injury prevention and first aid after tooth avulsion among young taekwondo athletes in Croatia. MATERIALS AND METHODS: A survey on a sample of 484 taekwondo athletes was conducted, which included 271 male (56%) and 213 female (44%) athletes aged between 8 and 28 years. The questionnaire submitted to the athletes contained 15 questions about dental trauma, use of mouthguard, dental trauma prevention, level of awareness about tooth avulsion and replantation and disturbances associated with mouthguard use. Collected data were evaluated according to gender, age groups and duration of actively engagement in taekwondo. Descriptive statistics and Chi-square tests were used for comparisons between groups. RESULTS: From the survey 300 (62%) of 484 athletes had sustained one serious injury and 103 (21%) had sustained an orofacial injury, while 194 (40%) had observed another player sustaining a dental injury. Higher number of orofacial injuries was observed in males (24%) than in females (18%). Furthermore, 98 (20%) athletes have experienced one or more dental injuries, and out of these 98 suffering dental injury 60 were male (61%) and 38 were female (39%). The frequency of orofacial injuries in the older group (42%) is higher than in three younger groups (younger cadets 25%; cadets 13%; juniors 20%) (p<0.05). Mouthguard wearing was recorded in 465 athletes (96%), 47.1% of them wear stock mouthguard, 47.6% wear boil and bite mouthguard, but only 5.3% were custom-made mouthguards. Most of them (96%) consider that mouthguards are useful for injury prevention in taekwondo. CONCLUSION: The results of this survey show that dental and orofacial injuries occur in taekwondo in all age groups but mostly in the senior group. Taekwondo players know the importance of mouthguard use, but only 5% use custom made mouthguards. This is not adequate for dental injury prevention and highlights the important role of dental professional in education of athletes for advocating the use of custom made mouthguards.

Exploratory computational assessment of possible binding modes for small molecule inhibitors of the CD40-CD154 co-stimulatory interaction.

Protein-protein interactions (PPI) tend to involve extensive, flat, and featureless interfaces that are difficult to disrupt by small molecule binding. However, recently, PPIs are being recognized as increasingly valuable 'druggable' targets. We have identified several small molecule inhibitors of the immunologically relevant CD40-CD154 co-stimulatory interaction that bind to the homotrimeric CD154, a member of the tumor necrosis factor superfamily (TNFSF). Recently, on the basis of the co-crystal structure of CD154 with another small molecule (BIO8898), it has been suggested that these PPIs could be particularly susceptible to small molecule blockade due to a subunit fracture mechanism resulting in a distortion of the trimeric structure. To investigate whether this mechanism can occur with our organic dye-related inhibitors, we performed exploratory computational docking experiments. Possible druggable pockets that can serve as binding sites for small molecule inhibitors were identified with the FFT map algorithm both along the CD154-CD40 binding interface (competitive, orthosteric model) and in the interior core of the CD154 trimer corresponding to the BIO8898 binding site (allosteric model). Docking experiments (using Glide) were performed at these sites using the PDB ID: 3QD6 (CD40-CD154) and 3LKJ (BIO8898-CD154) co-crystal structures, respectively. The docking algorithm was able to better discriminate binders from non-binders at the deeper allosteric site than at the competitive site. Accordingly, an allosteric inhibitory mechanism that involves intercalation between monomeric subunits seems feasible for our small molecules making the constitutively trimeric CD154 a likely druggable target.

Several natural indicators of radial well ageing at the Belgrade groundwater source, part 1.

Over time, the radial collector wells of the Belgrade Groundwater Source, located in the alluvial sediments of the Sava River, exhibit a decline in discharge and a reduction in operating efficiency due to well ageing. An increase in hydraulic losses at the lateral screens, due to chemical and biochemical clogging, has been identified as the primary cause. Certain hydrogeological, hydrochemical and microbiological parameters reflect the well-ageing process and can, therefore, be considered as its indicators. An indicator-based determination of scale is an important aspect in the selection of appropriate well locations, structural characteristics, and maintenance approaches. Well ageing was studied over a period of 5 years (2005-2009). The objective was to investigate the causes of well ageing. The correlations established between the groundwater redox potential, the total iron concentration in groundwater, the grain-size distribution of the aquifer, and well discharge, are presented in the paper.

Understanding loneliness: a systematic review of the impact of social prescribing initiatives on loneliness.

AIMS: The aim of this systematic literature review is to assess the impact of social prescribing (SP) programmes on loneliness among participants and the population. METHODS: We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to search EBSCOHost (CINAHL Complete, eBook Collection, E-Journals, MEDLINE with Full Text, Open Dissertations, PsycARTICLES, and PsycINFO), UK National Institute for Health and Care Excellence (NICE), Web of Science Core Collection, and grey literature. We included studies measuring the effectiveness and impact of SP programmes in terms of loneliness. We excluded systematic reviews and studies without evaluations. Due to the absence of confidence intervals and the low number of studies, we conduct no meta-analysis. RESULTS: From 4415 unique citations, nine articles met the inclusion criteria. The studies do not use uniform measures or randomised samples. All nine studies report positive individual impacts; three report reductions in general practitioner (GP), A&E, social worker, or inpatient/outpatient services; and one shows that belonging to a group reduces loneliness and healthcare usage. CONCLUSION: The findings of this systematic review indicate that individuals and service providers view SP as a helpful tool to address loneliness. However, evidence variability and the small number of studies make it difficult to draw a conclusion on the extent of the impact and the pathways to achieving positive change. More research is needed into the impact of SP programmes on participants, populations, and communities in terms of loneliness, isolation, and connectedness, especially in light of the surge in SP activity as a key part of pandemic response.

Self tolerance to T cell receptor V beta sequences.

T cell tolerance to self is achieved by deletion or inactivation of clones recognizing peptides of self proteins presented by major histocompatibility complex molecules. A considerable fraction of self proteins accessible to the immune system is contributed by the system itself, for example, the receptors used for antigen recognition (antibodies and T cell receptors [TCRs]). Thus far, it has remained unclear, whether antigen receptors are subject to self tolerance, or on contrary, engage into network interactions implying immunity rather than tolerance. In this study, we demonstrate self tolerance to synthetic peptides corresponding to the first hypervariable region of the V beta 8.1 and V beta 8.2 TCR proteins. We also show that the tolerogenic synthetic peptide corresponds to a fragment produced by processing of the V beta protein, and conversely, that a V beta peptide not produced by processing is also not subject to self tolerance. Thus, the rules of tolerance seem to apply to antigen receptors, at least to their germline-encoded portions, in a similar fashion as to other self proteins. This finding has important implications for studies of natural and artificially induced immune networks.

HLA-DR4-IE chimeric class II transgenic, murine class II-deficient mice are susceptible to experimental allergic encephalomyelitis.

To investigate the development of HLA-DR-associated autoimmune diseases, we generated transgenic (Tg) mice with HLA-DRA-IE alpha and HLA-DRB1*0401-IE beta chimeric genes. The transgene-encoded proteins consisted of antigen-binding domains from HLA-DRA and HLA-DRB1*0401 molecules and the remaining domains from the IE(d)-alpha and IE(d)-beta chains. The chimeric molecules showed the same antigen-binding specificity as HLA-DRB1*0401 molecules, and were functional in presenting antigens to T cells. The Tg mice were backcrossed to MHC class II-deficient (IA beta-, IE alpha-) mice to eliminate any effect of endogenous MHC class II genes on the development of autoimmune diseases. As expected, IA alpha beta or IE alpha beta molecules were not expressed in Tg mice. Moreover, cell-surface expression of endogenous IE beta associated with HLA-DRA-IE alpha was not detectable in several Tg mouse lines by flow cytometric analysis. The HLA-DRA-IE alpha/HLA-DRB1*0401-IE beta molecules rescued the development of CD4+ T cells in MHC class II-deficient mice, but T cells expressing V beta 5, V beta 11, and V beta 12 were specifically deleted. Tg mice were immunized with peptides, myelin basic protein (MBP) 87-106 and proteolipid protein (PLP) 175-192, that are considered to be immunodominant epitopes in HLA-DR4 individuals. PLP175-192 provoked a strong proliferative response of lymph node T cells from Tg mice, and caused inflammatory lesions in white matter of the CNS and symptoms of experimental allergic encephalomyelitis (EAE). Immunization with MBP87-106 elicited a very weak proliferative T cell response and caused mild EAE. Non-Tg mice immunized with either PLP175-192 or MBP87-106 did not develop EAE. These results demonstrated that a human MHC class II binding site alone can confer susceptibility to an experimentally induced murine autoimmune disease.

Comparison of Surgisis, Vypro II and TiMesh in contaminated and clean field.

PURPOSE: The study aimed to evaluate the histologic properties and infection resistance of three different mesh materials in a rat model. METHODS: Each mesh, in both infectious (n = 96) and non-infectious groups (n = 270), was positioned both in sublay (preperitoneally) and onlay (subcutaneously) locations. Properties of the biological (Surgisis; Cook Surgical), composite, partially resorbing (Vypro II mesh; Ethicon) and non-resorbing (TiMesh; GFE Medizintechnik GmbH) mesh were evaluated and compared. Animals were killed at 7, 21 and 90 days after implantation. The following parameters were evaluated to assess the host response to the mesh material: inflammation, vascularization, fibrosis, collagen formation, Ki67, and a foreign body reaction by granuloma formation (FBG). RESULTS: Surgisis mesh produced more pronounced inflammation and cell proliferation, and less intense granuloma formation, as well as fibrosis, compared to the other two groups. When the infected materials were examined, we found signs of local infection to be more often present in Surgisis group of animals. CONCLUSIONS: In the presence of bacterial contamination, no benefits were observed in the use of the Surgisis prosthesis over the use of TiMesh and Vypro II.

Enhanced major histocompatibility complex class I-dependent presentation of antigens modified with cationic and fusogenic peptides.

Soluble extracellular protein antigens are notoriously poor stimulators of CD8+ cytotoxic T-lymphocyte (CTL) responses, largely because these antigens have inefficient access to an endogenous cytosolic pathway of the major histocompatibility complex (MHC) class I-dependent antigen presentation. Here, we present a strategy that facilitates antigen penetration into the cytosol of antigen-presenting cells (APC) by addition to the antigen of charge-modifying peptide sequences. As a result of this intervention, the charge modification enhances antigen uptake into APC by counteracting the repulsive cell surface charge, and then endosomal membranes are disrupted with a subsequent release of antigen into the cytosol. This technology significantly improves MHC class I-dependent antigen presentation to CTL, enabling a more efficient generation of specific CTL immunity in vivo. The strategy described here has potential for use in developing efficient vaccines for antigen-specific immunotherapy of human malignancies.

Peptidomimetic compounds that inhibit antigen presentation by autoimmune disease-associated class II major histocompatibility molecules.

We have identified a heptapeptide with high affinity to rheumatoid arthritis-associated class II major histocompatibility (MHC) molecules. Using a model of its interaction with the class II binding site, a variety of mimetic substitutions were introduced into the peptide. Several unnatural amino acids and dipeptide mimetics were found to be appropriate substituents and could be combined into compounds with binding affinities comparable to that of the original peptide. Compounds were designed that were several hundred-fold to more than a thousand-fold more potent than the original peptide in inhibiting T-cell responses to processed protein antigens presented by the target MHC molecules. Peptidomimetic compounds of this type could find therapeutic use as MHC-selective antagonists of antigen presentation in the treatment of autoimmune diseases.

Alkene-assisted cis-to-trans isomerization of non-conjugated polyunsaturated alkenes.

Complex [Cp*Ru(NCMe)3][PF6], 1a, has been identified as a cis-to-trans isomerization catalyst of various non-conjugated cis-polyalkenes under exceptional kinetic control as no alkene conjugation was observed. According to the experimental and theoretical data, the cis-trans isomerization occurred via an alkene-assisted mechanism in which one cis-double bond always served as an anchoring site. Using a combination of multinuclear NMR spectroscopic evidence and mathematical methods it was possible to determine the extent of trans isomerization.

Factors affecting recurrence after incisional hernia repair.

Incisional hernias occur primarily as a result of high tension and inadequate healing of a previous incision, the latter of which is frequently related to infection at the surgical site. Despite recent advances in operative techniques, the recurrence rate remains unacceptably high. To evaluate the impact of different predisposing factors for the recurrence of incisional hernia, we reviewed retrospectively the medical records of 297 patients who had undergone incisional herniorrhaphy (188 tissue repairs, 109 mesh repairs) in our hospital. Demographic data (age and gender), type of repair, body mass index, hernia size, presence of chronic illnesses and wound complications were evaluated in a univariate and multivariate manner analysis. The overall recurrence rate was 30.3%, with the recurrence rate in patients who underwent tissue repair being 39.4% and that in patients following prosthetic repair 14.6%. The recurrence rate was significantly influenced by type of repair, obesity, hernia size, wound healing disorders and some chronic comorbidities. We conclude that it is necessary to become familiar with the risk factors for recurrence of incisional hernia in order to eliminate or decrease their effect on the positive outcome of incisional herniorrhaphy.

Unusual attempted suicide by shooting through heart.

Gunshot wounds in the heart are frequent suicidal injuries, especially in men. Most of them are lethal, but some cases of survival due to immediate and proper surgical treatment are reported. However, survival without specific treatment is extremely rare. In our case, a 44-year man attempted suicide by home-made shooting device. A special 12 cm long and 2.5 mm wide needle-like missile entered his body at the left anterior part of his chest, passed through the heart and lower lobe of right lung and exited at the right side of his back. The patient was able to move normally and he also looked for medical help immediately after attempting suicide. We found large atypical-shaped entrance wound on the anterior part of the chest, which was surgically treated, and tiny pointed exit wound under the right scapula. The patient was stable from cardio-circulatory and respiratory aspects from the time of admission to discharge from the hospital. We found only minimal pericardial bleeding (up to 10 mm thick) and there was no need for surgical intervention. In the next 2 weeks the haematoma absorbed spontaneously. The gunshot injury healed without any complication. Paranoid psychosis was diagnosed by psychiatrist and this probably had been the cause of attempting suicide. We think that the favorable outcome of the proved heart gunshot injury in our patient was due to the needle-shaped low-energy missile, which caused only tiny gunshot (stab) hole in the heart. Such a heart injury caused only minimal bleeding into the pericardial sac without heart tamponade.

Correction: Iminoborylene complexes: evaluation of synthetic routes towards BN-allenylidenes and unexpected reactivity towards carbodiimides.

Correction for 'Iminoborylene complexes: evaluation of synthetic routes towards BN-allenylidenes and unexpected reactivity towards carbodiimides' by J. Niemeyer et al., Dalton Trans., 2015, DOI: 10.1039/c5dt00131e.

Iminoborylene complexes: evaluation of synthetic routes towards BN-allenylidenes and unexpected reactivity towards carbodiimides.

The synthetic and reaction chemistries of cationic iminoborylene complexes [LnM=B=N=CR2](+), which feature a unique heterocumulene structure, have been systematically investigated. Precursors of the type CpFe(CO)2B(Cl)NCAr2 (Ar = p-Tol/Mes, 5c/d) have been generated by B-centred substitution chemistry using CpFe(CO)2BCl2 and suitable lithiated ketimines - a reaction which is found to be highly sensitive to the steric bulk at both the metal fragment and the ketimino group. Carbonyl/phosphine exchange (using PCy3 or PPh3), followed by halide abstraction allows for the generation of the cationic iminoborylenes [CpFe(PR3)(CO)(BNCAr2)](+)[BAr(X)4](-) (R = Cy, Ar = p-Tol/Mes, 12c/d; R = Ph, Ar = Mes, 13d; Ar(X) = 3,5-X2C6H3 where X = Cl, CF3) which have been characterized spectroscopically and by X-ray crystallography. The reactivity of these iminoborylene systems towards a range of nucleophiles and unsaturated substrates has been investigated. The latter includes the first examples of M=B metathesis reactivity with a carbodiimide, and results in Fe=B cleavage and formation of the isonitrile complexes [CpFe(PCy3)(CO)(CNR)](+)[BAr(Cl)4](-) (R = (i)Pr/Cy, 16/17).

Should we abandon regional anesthesia in open inguinal hernia repair in adults?

Inguinal hernia repair is a common worldwide surgical procedure usually done in the outpatient setting. The purpose of this systematic review is to make an evidence-based meta-analysis to determine the possible benefits of regional (neuraxial block) anesthesia compared to general anesthesia in open inguinal hernia repair in adults. Cochrane Library, Medline, EMBASE, CINAHL, SCI-EXPANDED, SCOPUS as well as trial registries, conference proceedings and reference lists were searched. Only randomized controlled trials (RCT) that compare neuraxial block (spinal or/and epidural) anesthesia (NABA) and general anesthesia (GA) were included. Main outcome measures were postoperative complications, urinary retention and postoperative pain. Seven RCTs were included in this review. A total of 308 patients were analyzed with 154 patients in each group. Overall complications were evenly distributed in NABA and in GA group [OR 1.17, 95 % CI (0.52-2.66)]. Urinary retention was statistically less frequent in GA group compared to NABA group [OR 0.25, 95 % CI (0.08-0.74)]. Movement-associated pain score 24 h after surgery was significantly lower in NABA group [SMD 5.59, 95 % CI (3.69-7.50)]. Time of first analgesia application was shorter in GA group [SMD 8.99, 95 % CI 6.10-11.89]. Compared to GA, NABA appears to be a more adequate technique in terms of postoperative pain control. However, when GA is applied, patients seem to have less voiding problems.

Peptide and peptide mimetic inhibitors of antigen presentation by HLA-DR class II MHC molecules. Design, structure-activity relationships, and X-ray crystal structures.

Molecular features of ligand binding to MHC class II HLA-DR molecules have been elucidated through a combination of peptide structure-activity studies and structure-based drug design, resulting in analogues with nanomolar affinity in binding assays. Stabilization of lead compounds against cathepsin B cleavage by N-methylation of noncritical backbone NH groups or by dipeptide mimetic substitutions has generated analogues that compete effectively against protein antigens in cellular assays, resulting in inhibition of T-cell proliferation. Crystal structures of four ternary complexes of different peptide mimetics with the rheumatoid arthritis-linked MHC DRB10401 and the bacterial superantigen SEB have been obtained. Peptide-sugar hybrids have also been identified using a structure-based design approach in which the sugar residue replaces a dipeptide. These studies illustrate the complementary roles played by phage display library methods, peptide analogue SAR, peptide mimetics substitutions, and structure-based drug design in the discovery of inhibitors of antigen presentation by MHC class II HLA-DR molecules.

Influence of CD26 and integrins on the antigen sensitivity of human memory T cells.

The antigen sensitivity of class II MHC restricted human CD4 T-cell clones is demonstrated to increase gradually with time after restimulation. This is manifested in a requirement of less antigen in culture, as well as decreased numbers of peptide-MHC complexes per APC for T-cell activation, and in an increased resistance to inhibition by class II MHC blockade. The increase in antigen sensitivity is accompanied by increased cell-surface expression of CD26, LFA-1, and VLA-1, whereas the expression of TCR and a series of other cell-surface molecules remains unchanged. Using appropriate monoclonal antibodies, we have shown that CD26 and LFA-1 contribute directly to the increased antigen sensitivity of "late-stage" T-cell clones. The late-memory T-cell phenotype established in this study is shown to occur also among T cells activated in vivo. We suggest that increasing the antigen sensitivity via antigen-nonspecific molecules is a physiologic mechanism for maintaining T-cell memory in face of decreasing antigen concentration, and for ensuring preferential activation of memory T cells upon repeated encounter with antigen.

Selective apoptosis of neoplastic cells by the HLA-DR-specific monoclonal antibody.

The human major histocompatibility complex (MHC) class II molecule-specific monoclonal antibody (mAb) 8D1 can induce apoptosis of tumor cells expressing HLA-DR molecules on their surface. This effect is associated with a cross-linking of HLA-DR, since monovalent Fab fragments of 8D1 cannot mediate cytotoxicity unless they are anchored to a solid support. Anti-neoplastic activity of 8D1 is highly selective, i.e. the mAb affects neither the viability nor the function of non-malignant HLA-DR+ cells. These findings raise the possibility of a selective antibody-based anti-tumor therapy of class II positive blood cell neoplasm.