The structural creep activity under eccentric compression is significantly larger because of the interaction between creep and cracking, i.e. bending-induced cracks progressively open and propagate under sustained eccentric loading. As for concrete hinges in frame-like integral bridge construction, it is concluded (i) that realistic simulation of variable loads requires consideration of the here-studied time-dependent behavior and (ii) that permanent compressive normal forces shall be limited by 45% of the ultimate load carrying capacity, in order to avoid damage of concrete hinges under sustained loading.Existing design guidelines for concrete hinges consider bending-induced tensile cracking, but the structural behavior is oversimplified to be time-independent. This is the motivation to study creep and bending-induced tensile cracking of initially monolithic concrete hinges systematically. Material tests on plain concrete specimens and structural tests on marginally reinforced concrete hinges are performed. The experiments characterize material and structural creep under centric compression as well as bending-induced tensile cracking and the interaction between creep and cracking of concrete hinges. As for the latter two aims, three nominally identical concrete hinges are subjected to short-term and to longer-term eccentric compression tests. Obtained material and structural creep functions referring to  Concrete hinges were invented by Freyssinet , 2. TheyCurrent design guidelines for concrete hinges are based on pioneering developments of Leonhardt and Reimann . In the Concrete hinges are nowadays experiencing a renaissance in integral bridge construction. Examples are (i) the viaduct “Weißenbrunn am Forst”, Germany, which was constructed in 2011, see , and  structural creep under centric loading, (ii) tensile cracking under short-term eccentric loading, (iii) structural creep under eccentric compression at virtually 25% of the ultimate load carrying capacity, and (iv) the interaction between bending-induced tensile cracking and creep. Rotations of the concrete hinges are quantified by means of Inductive Displacement Transducers (LVDTs). Crack propagation is observed with a non-contact displacement measurement system, based on Digital Image Correlation (DIC).The present contribution is structured as follows. Materials and test specimens are discussed in Sect. E are determined 28 days after production, following the Austrian standards for testing of concrete [Concrete C 35/45 F45 GK16 B5  is produconcrete , as1\docnt}fc as 2\documenAs for the rebars, steel quality B550 A was chosen. The von Mises yield stress As for material testing of plain concrete, 10 prisms are produced. They exhibit nominal dimensions of 75 mm entclass1pt{minimaAs for structural testing, three marginally reinforced concrete hinges are produced. Their geometric shape (i) is inspired by the concrete hinges of Huyck-bridge , and  system of type Dantec Dynamics Q 400, is used to observe tensile crack propagation along the notch roots of the front side and the back side notches. To this end, both notches are monitored with a pair of 5 megapixel cameras each. Application of two cameras per notch allows for recording three-dimensional displacement fields, whereby the in-plane displacements are of special interest. The observed field of view is approximately equal to 12 cm Centric compression tests up to 200 kN are used to characterize the extensional stiffness of undamaged concrete hinges and their structural creep behavior under pure normal force (no bending). To this end, each of the three concrete hinges is installed into the testing machine, resting on temporary supports. After fine tuning the position and installing the deformation measurement equipment, loading is increased up to 4 kN. This allows for removing the temporary supports, because 4 kN loading is sufficient to keep the concrete hinge in the desired position (no tipping over). Reference readings of the deformation measurement system are taken. Finally, the loading is increased with a force rate amounting to 5 kN/s up to 200 kN. This loading is kept constant for 4 h, followed by complete unloading, using again the force rate of 5 kN/s.e and of the compressive normal force N. This requires a careful development of the test design described next.Minutes-long eccentric compression tests are used to characterize (i) the bending stiffness of undamaged concrete hinges and (ii) the development of tensile cracking as a function of the eccentricity undamaged bending stiffness of the investigated concrete hinges, a trade off must be found between (i) a large eccentricity, resulting in relatively large bending, see Eq.  the structural creep behavior under combined compression and bending as well as (ii) the interaction between creep and bending-induced tensile crack propagation. With these two aims in mind, continued testing of concrete hinges was organized as follows.A 16 h-long creep test is carried out with eccentricity A second set of structural tests deals with the load carrying capacity of concrete hinges subjected to eccentric loads. These tests are carried out in order to characterize the relation between eccentric loading and rotation angle, up to structural failure.Concrete hinges are subjected, 40 days after production, to compressive line loads using a servo-hydraulic testing machine of type Schenk POZ 0367. The load carrying capacity tests are carried out with an eccentricity of Eight LVDTs of type HBM WI 10 are mounted to the lateral surfaces of the concrete hinges, in order to measure changes of the notch mouth opening displacements of the lateral notches. The measurement length in loading direction amounts to N is increased up to the load carrying capacity. After installing the respective concrete hinge into the testing machine, fine tuning the position, installing the deformation measurement equipment, preliminary loading up to 1 kN, removal of the temporary supports, and taking reference readings of the deformation measurement system, the line-load is increased. This is carried out by manually increasing the displacement of the load application system, with a target rate amounting to 0.2 mm/min. Once 100 kN is reached, the loading process is stopped for 1 min, in order to quantify the time-dependent structural response at that load level. After that, loading is increased by another 100 kN, followed by the next waiting period. Step by step loading is increased up to the load carrying capacity. The latter is assumed to be reached once the rotation angle increases significantly while no significant increase of the normal force is observed. Unloading is performed by using again the rate of 0.2 mm/min. The duration of one test is approximately 30 min.In eccentric compression tests  are averagedThe five creep tests performed under All three concrete hinges showed virtually the same behavior during the creep tests. The force-shortening relationships during 40 s-long loading are practically linear. The shortening of the neck, just after arriving at 200 kN, amounts to Increasing eccentric loading in steps of 25 kN and interrupting the loading process for 5 s at each completed loading step, demonstrates that concrete hinges are very creep active even under small degrees of utilization (relative to the load carrying capacity), see the visible load plateaus highlighted in red color in Fig. When it comes to identification of crack length at the different load plateaus, we consider a region to be cracked, if the maximum strain in loading direction is larger than a threshold. Definition of the latter is a challenging task given the small strain amplitudes before tensile cracking. We here defined an upper and a lower threshold which are expected to be bounds containing the real crack initiation strain, see Table All three concrete hinges showed virtually the same behavior during the eccentric creep tests. The relationships between the eccentric force and the rotation angle are practically linear during the loading period amounting to 35 s. The rotation angle of the neck, just after arriving at 175 kN, amounts to The behavior of the pre-existing crack under constant eccentric loading  developed inside the concrete hinges even before mechanical loading. The tensile stresses may have well resulted in damage of concrete, in form of microcracking. This effect was already pointed out in 1965 by Leonhardt and Reimann , see SecIn , elasto-mount to 17\documeDuring the short term loading experiments carried out with eccentricity found in  and, henThe herein measured material and structural creep properties are qualitatively similar, see the “power-law”-type normalized creep evolutions in Fig. The material tests and the centric structural experiments delivered also quantitatively very similar normalized creep evolutions, particularly so during the first hour of the tests, see Fig. The described quantitative differences allow for the announced checking of the plausibility of the damaged elastic stiffness value of concrete reported in Eq. . In thisspecimen , where \ to Eqs. , and  cracks will close in the vicinity of the crack tip and (ii) crack opening displacements will decrease elsewhere.The by far largest normalized creep activity was measured in the eccentric tests on initially monolithic concrete hinges. This underlines a considerable interaction between creep additional drying happened during the creep tests and the measured creep behavior refers to basic creep of pre-dried specimens. Also, the performed creep tests were very short compared to real application cases. This is the motivation to discuss decades long creep processes in Sect. The described creep tests had a characteristic duration ranging from 12 to 20 h. This is negligibly short as compared to 24 days which is the period of drying ranging from stripping of the formworks to the start of the creep tests. Therefore, no significant total compliance of concrete, related to both instantaneous elastic and delayed time-dependent deformation, would be twice as large as the instantaneous compliance.Existing design guidelines either disregard the time-dependent behavior of concrete hinges or consider it in a very simplified manner. The model by Gladwell  was deriCreep under a sustained bending moment results in a progressive increase of the relative rotation angle, see the abscissa-parallel chains of data points in Fig. Relaxation under an imposed relative rotation angle, in turn, results in a progressive reduction of the bending moment, see the ordinate-parallel arrow in Fig. In integral bridge construction, however, concrete hinges experience bending loads which do not refer to perfect creep or relaxation scenarios, as discussed next for the important exemplary case of frame-type integral bridges.Creep of concrete, however, does not come to an end: it starts with power-law-type creep rates and decays later to logarithmic creep rates which do not approach a stable asymptotic value . This isOnce a frame-type bridge is completed, dead load of the structure is transmitted across concrete hinges positioned, e.g., at the feet of the columns. Therefore, each concrete hinge is subjected to a compressive normal force and to a bending moment. The viscoelastic behavior of concrete results in a progressively increasing rotation angle at the neck of the concrete hinge. As a feedback from the statically indeterminate structure, the bending moment at the concrete hinge decreases. In other words, the time-dependent behavior of concrete hinges results in load redistributions within the bridge structure, such that—asymptotically—a vanishing bending moment at the concrete hinge will be obtained. Therefore, modeling concrete hinges as classical hinges without bending stiffness is a well-suited approach for the simulation of the finally reached structural state under permanent loading. The corresponding normal forces, however, have to be transmitted across the concrete hinges permanently. In order to avoid the risk of nonlinear creep in compression, i.e. the interaction between creep and progressive damage –54, it iVariable loads, such as the ones resulting from daily changes of the ambient temperature, exhibit characteristic times which are equal to the ones studied in the present creep experiments. This implies that modeling concrete hinges as rotational springs with a time-dependent stiffness is required for realistic structural simulations in integral bridge construction. The herein characterized mechanical properties of concrete and the experimental data obtained in the structural tests are well suited to support these future modeling activities. In this context, it is noteworthy that the structural tests with forces Concrete hinges are very creep active structures. The creep-related shortening of the neck under centric compression increased in 4 h by 20 % relative to the shortening developing during loading Fig. . The creCreep and bending-induced tensile cracking of concrete hinges are interacting phenomena. Creep under eccentric compression increases the length and opening displacements of bending-induced tensile cracks. The increased crack length, in turn, amplifies the structural creep activity relative to material or structural creep under centric compression Fig. .Vice versa, stress relaxation will result in partial crack closure and in decreasing crack opening displacements, which is very beneficial for the durability of concrete hinges.As for the simulation of initially monolithic concrete hinges in frame-like integral bridge construction, the following conclusions are drawn:without bending stiffness is a sound approach for assessing the finally reached structural state.As for permanent loads, modeling of concrete hinges as classical hinges In order to avoid progressive damage under permanent compressive normal forces, the latter shall be limited to 45 % of the corresponding ultimate load carrying capacity of the concrete hinge.time-dependent stiffness is required for reliable simulations.As for variable loads, future modeling of concrete hinges as rotational springs with The presented experimental data may well support such future modeling activities.From the obtained experimental data and from the related discussions, the following conclusions are drawn:


Senior participants (age ≥55 years) with MCI were randomized to the MET or yogic meditation interventions. For both interventions, participants completed either MET training or Kundalini Yoga (KY) for 60-min sessions over 12 weeks, with 12-min daily homework assignments. Gray matter volume and metabolite concentrations in the dorsal anterior cingulate cortex (dACC) and bilateral hippocampus were measured by structural MRI and 1H-MRS at baseline and after 12 weeks of training. Metabolites measured included glutamate-glutamine (Glx), choline-containing compounds , gamma-aminobutyric acid (GABA), and N-acetyl aspartate and N-acetylaspartyl-glutamate (NAA-NAAG). In total, 11 participants completed MET and 14 completed yogic meditation for this study. Structural MRI analysis showed an interaction between time and group in dACC, indicating a trend towards increased gray matter volume after the MET intervention. 1H-MRS analysis showed an interaction between time and group in choline-containing compounds in bilateral hippocampus, induced by significant decreases after the MET intervention. Though preliminary, our results suggest that memory training induces structural and neurochemical plasticity in seniors with MCI. Further research is needed to determine whether mind-body interventions like yoga yield similar neuroplastic changes.Behavioral interventions are becoming increasingly popular approaches to ameliorate age-related cognitive decline, but their underlying neurobiological mechanisms and clinical efficiency have not been fully elucidated. The present study explored brain plasticity associated with two behavioral interventions, memory enhancement training (MET) and a mind-body practice (yogic meditation), in healthy seniors with mild cognitive impairment (MCI) using structural magnetic resonance imaging (s-MRI) and proton magnetic resonance spectroscopy ( The global population is aging at a rate unprecedented in human history. About 98 million people will be over 65 years old by 2060  to measure brain metabolites. We targeted four metabolite peaks with 1H-MRS previously linked to cognitive function  and KY + KK yoga affect brain plasticity in two areas of the brain important for memory and cognition, the bilateral hippocampus and dorsal anterior cingulate cortex (dACC). We used structural magnetic resonance imaging (s-MRI) to measure gray-matter volume and proton magnetic resonance spectroscopy  age ≥55 years; (2) a diagnosis of MCI-amnestic type by standard criteria . Clinical measurements included the Geriatric Depression Scale  classes. Each group was assigned approximately 12 min of daily homework specific to the intervention. In total, 25 participants (11 MET and 14 yogic meditation) finished the study.Memory training (MET) was developed from evidence-based techniques that involve teaching verbal and visual association strategies and other practical strategies to improve memory function. We chose to implement mnemonic methods over computerized memory training programs because the former have a longer history of implementation in aging populations, have been studied more, with much empirical evidence supporting their use in elders.The KY + KK intervention was conducted by a certified yoga teacher. The KY + KK class included teaching body-movement and mindfulness exercises, specifically: (1) Tuning in (5 min); (2) Warm up (10 min); (3) Pranayam (10 min); (4) Kriya (20 min); (5) Meditation (11 min); and (6) Shavasana (4 min). This standard 12-min KY + KK meditation protocol as created by Yogi Bhajan was taught by the certified yoga teacher. Adverse events were monitored at each visit by using the UKU Side Effect Rating Scale  and bilateral hippocampal gray matter  was used for automated cortical surface reconstruction and cortical/subcortical parcellation estimation on each subject’s structural image. Freesurfer morphometric procedures have been demonstrated to show good test-retest reliability across scanner manufacturers and across field strengths  and full width at half-maximum (FWHM) values are also listed for reference for each metabolite. In dorsal ACC: for GABA, 1 Yoga baseline, 3 Yoga follow-up, 3 MET baseline, 1 MET follow-up were excluded ; for Glx, 1 Yoga baseline, 2 Yoga follow-up, 3 MET baseline, 1 MET follow-up were excluded ; for Cho, 1 Yoga follow-up, 2 MET baseline, 1 MET follow-up were excluded ; NAA/NAAG 1 follow-up, 2 MET baseline, 1 MET follow-up were excluded . In bilateral hippocampus: for Glx, 1 Yoga baseline, 1 follow-up, 1 MET follow-up were excluded ; for NAA/NAAG 2 Yoga baseline, 1 Yoga follow-up were excluded , for Cho .t-tests or chi-squared tests. All structural measures and metabolites of interest were analyzed by a mixed effects general linear model (implemented in SAS PROC MIXED), using intervention group, time and the interaction term between time and group as predictors. In analyses of gray-matter volume, total intracranial volume was entered as an additional covariate, and in analyses of hippocampal volume and metabolites, both ROIs were analyzed in the same model with hemisphere  entered as an additional within subject factor. Post hoc analyses tested within group changes as well as changes between groups with time. As this is an exploratory study to examine how brain structures and metabolites change due to the interventions, we did not correct for multiple comparisons and significance levels were set at 0.05, two-tailed.For all demographic and clinical measures, the two interventions were compared at baseline by p > 0.2).Table d) for gray-matter volume changes  = 1.35, p = 0.25) indicating that change in hippocampal volume did not differ between the two interventions. In dACC, there was a significant interaction term  = 4.86, p = 0.04); the memory training group showed a trend towards increased volume after training (t(22) = 1.73, p = 0.1) while the yoga group did not show any change (t(22) = 1.38, p = 0.2). Further, there were no significant main effects of group or time for either region.We examined gray-matter volume changes after yoga and memory training in bilateral hippocampus and dACC Table . An effe1H-MRS analyses, we analyzed Glx, NAA/NAAG, and Cho values, as well as the effect size for the comparisons in bilateral hippocampus and dACC. GABA was also estimated in the dACC using spectral editing as described above  = 4.35, p = 0.04; See Table Post hoc analyses showed that choline decreased in the memory training group (t(38) = −2.58, p = 0.01), but did not change in the yoga group (t(38) = 0.30, p = 0.8). Of note, though all other measures were similar across treatment groups, hippocampal choline was greater in the memory training group at baseline than the yoga group (t(38) = 2.17, p = 0.04). No other metabolites exhibited significant interaction terms, nor were there significant main effects of group or time for any metabolite for the hippocampus. In the dACC, there were no significant interactions or main effects identified for any metabolites.For Table F1,8 = 4.35,We explored whether the changes for clinical measures correlated with the structural or brain chemical changes. None of the correlations between the MRI or MRS changes and GDS or MMSE changes were significant. Note also that followup measures were also reported previously  can modestly increase cortical gray matter in dACC, a region of the brain linked to multiple key cognitive functions, such as error detection , and 2014 National Alliance for Research on Schizophrenia and Depression (NARSAD) Young Investigator Grant from the Brain and Behavior Research Foundation (22325).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer AJW and handling Editor declared their shared affiliation, and the handling Editor states that the process nevertheless met the standards of a fair and objective review.


IgG4-related disease (IgG4-RD) is a recently recognized disorder, characterized by elevated serum IgG4 concentrations, dense tissue infiltration of IgG4-positive plasma cells and storiform fibrosis. Treatment is usually based on steroids, however, relapses and long-term adverse effects are frequent. We prospectively studied 5 consecutive patients with histologically-proven IgG4-RD and renal involvement, treated with an extended Rituximab protocol combined with steroids. Two doses of intravenous cyclophosphamide were added in 4 patients.Five patients with IgG-RD were investigated: three had tubulointerstitial nephritis (TIN), while two had retroperitoneal fibrosis (RPF). In the patients with TIN, renal biospy was repeated after 1 year.2; IgG/IgG4 decreased from 3,236/665 to 706/51 mg/dl; C3/C4 increased from 49/6 to 99/27 mg/dl; CD20+ B-cells decreased from 8.7% to 0.5%; Regulatory T-cells decreased from 7.2% to 2.5%. These functional and immunologic changes persisted at 24 months and in two patients at 36 months. A repeat renal biopsy in the patients with TIN showed a dramatic decrease in interstitial plasma cell infiltrate with normalization of IgG4/IgG positive plasma cells. The patients with RPF showed a huge regression of retroperitoneal tissue.In the patients with TIN, estimated glomerular filtration rate (eGFR) at 12 months increased from 9 to 24 ml/min per 1.73 mIn this sample of patients with aggressive IgG4-RD and renal involvement, treatment aimed at depleting B cells and decreasing antibody and cytokine production was associated with a substantial, persistent increase in eGFR, and a definite improvement in immunologic, radiologic and histological parameters. In fact, CD4egulated . A polaregulated , 8, 9. LThe kidney is involved in approximately 15% of patients –6, 8. ReIgG4-related TIN patients may present progressive renal failure, mild to moderate proteinuria, leukocyturia, and mild haematuria , 15–17. 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) play an important diagnostic role in IgG4-RKD, in particular in patients with RPF, and are useful tools for monitoring therapeutic response and guiding interventional treatment [Contrast-enhanced computerized tomography (CT), magnetic resonance imaging (MRI) and reatment , 12, 19.Glucocorticoids are the first line of therapy for both IgG4-RD , 9, 20 aWe previously reported the favourable outcome of a cohort of patients with severe SLE treated with intensive B cell depletion therapy (IBCDT) consisting of a combination of 4 plus 2 infusions of RTX, cyclophosphamide and methylprednisolone pulses . This apIn the present study the effectiveness of IBCDT on clinical, biochemical, radiological and histologic parameters has been evaluated in patients with severe IgG4-related TIN and IgG4-related RPF.2. This improvement persisted at 24 months , and at 36 months in patients #1 and #2 . eGFR values also improved at 12, 24 and 36 months in patient #4 (from 48 to 74 ml/min per 1.73 m2 ), while in patient #5, who had RPF and bilateral ureteral stents, values remained stable six months after stent removal (from 44 to 49 ml/min per 1.73 m2).Table All immunologic parameters showed a definite improvement at 1 year in TIN patients . In particular, total serum IgG decreased from 3,236  to 706  mg/dl; likewise, IgG4 subclass decreased from 665  to 51  mg/dl. Complement mean level increased to normal: C3 went from 49  to 99  mg/dl; C4 rose from 6  to 27  mg/dl.+ B-cells decreased from the pre-treatment mean value of 8.7%  to 0% seven days after the 4th infusion (data not shown), and showed a mild increase to 0.5%  after 12–15 months.CD20Circulating regulatory T-cells  decreased from 7.2%  to 2.5%  at one year.+ B-cells (from 0 to 4.4%) and Treg cells (from 2.2 to 6.1%) at 24 months.The overall changes in immunological parameters persisted at 24 months and in patients #1 and #2 even at 36 months. Interestingly, patient #3, who had not received cyclophosphamide due to a past history of colon cancer, showed a definite increase in CD20+ B-cells and Treg cells decreased as expected due to the immunosuppressive treatment, while C3 and C4 levels, that were already normal, remained unchanged.In the two patients with RPF total IgG, IgG4, CD20Patients #1, #2 and #3 underwent a second renal biopsy 12 months after the first procedure.Figures In particular, the first biopsy in patient #1showed a more densely cellular inflammatory lesion with expansile storiform interstitial fibrosis involving about 80% of the examined material; in the second biopsy there was a marked reduction of storiform interstitial fibrosis that occupied only about 5% of the evaluated material, with an associated evident decrease of the inflammatory component. Furthermore, immunofluorescence of the first biopsy demonstrated the presence of granular immune deposits  in the tubular basement membrane which became negative in the second one. In patient #2 the amount of interstitial fibrosis remained substantially unchanged between the two biopsies, conversely there were only scattered plasma cells with a normal IgG4/IgG ratio in the second one. In patient #3 there was a mild reduction of interstitial fibrosis between the two biopsies, but the second one showed only focal aspects with a storiform pattern and occasional plasma cells.+ plasma cells/HPF.Figure + B-cells, Treg cells) showed any changes that might suggest this disease relapse. The patient was therefore treated with oral steroids which were gradually tapered during the following 3 months, and with RTX 375 mg/m2 every 4 months, showing again a gradual reduction of retroperitoneal tissue in MRI and PET/CT studies.Figure Figure Patients #1 and #2 developed steroid-induced diabetes mellitus requiring transient insulin therapy that was eventually discontinued in conjunction with prednisone discontinuation.Patient #4 developed mild, acute bronchopneumonia during the course of immunosuppressive treatment, which was rapidly and completely controlled by oral antibiotics.Glucocorticoids represent the first line of therapy for both IgG4-RD  and IgG4-RKD .A starting prednisolone dose of 0.6–1.0 mg/kg/daily, gradually tapered after 2–4 weeks depending on the clinical response, is the usual approach for IgG4-RD patients with organ failure, in particular in cases of type 1 autoimmune pancreatitis, and clinical and laboratory improvements are frequently rapid, depending on the affected organs and the degree of fibrosis . NeverthRTX has been shown to be effective in improving clinical and serologic features of IgG4-RD patients with active inflammation –23, evenSteroids are effective for most patients with IgG4-related TIN , 16, 21 An international panel of experts very recently developed some recommendations for the management of IgG4-RD, confirming glucocorticoids as first-line agents for remission induction in all patients with active, untreated disease (94% agreement). Conversely, there was lower agreement (46%) on the use of steroid-sparing agents, including RTX , possiblIn the present case series, we treated 1 patient who had IgG4-related TIN with a combination therapy of steroids and RTX, and 4 patients (2 with IgG4-related TIN and 2 with IgG4-related RPF) with the intensified immunosuppressive protocol adopted in our Department for severe SLE nephritis , 28. In The rationale for the combination therapy with small doses of cyclophosphamide over rituximab alone relies both on taking advantage of the synergic effects with RTX on CD20 positive cells and on expanding immunomodulation over a wider spectrum of B cells like plasmablasts also inhibiting their antigen presenting cell function. In our opinion this intensified treatment could be taken into consideration in patients with very aggressive clinical and histologic forms of IgG4-RKD and who may require more rapid and efficient induction therapy. Due to the small sample of patients additional studies are required to confirm this observation.+ B-cells (from 0 to 4.4%) and Treg cells (from 2.2 to 6.1%) at 24 months; the less aggressive immunosuppression may have facilitated this increase, but whether these immunologic modifications might predict disease relapse remains to be confirmed.Actually, patients with IgG4-related TIN, characterized by extremely reduced eGFR at presentation showed a remarkable response both in renal function and in immunologic parameters. Despite the severity of the disease in our series, these effects still persisted without any further immunomodulatory or anti-inflammatory therapy 2 years later, which is in line with the results already observed in severe SLE patients with long term follow-up (44 months) . Furtheret al. [Normalization of circulating regulatory T-cells at the end of therapy, together with the functional, immunological and histological improvement observed in our TIN patients support a role for these cells in the pathogenesis of IgG4-RD as proposed by Takeuchi et al.  and suggWith regard to IgG4-related RPF, the high recurrence rate often requires maintenance immunosuppressive therapy . The cliThe main limitations of our study are the small number of patients, the population heterogeneity and the limited follow-up. In particular, the three patients with TIN showed different immunologic parameters as compared to RPF patients including higher levels of serum IgG, IgG4, circulating T regulatory cells, and lower complement levels. Some of these features have been already described , 13, 14,The main strength of this study is that it is the first case series study to include repeat renal biopsies. Re-examination of histology one year after diagnosis and therapy helps guide further therapeutic decisions, provides insight into the possible progression of the disease or, as in our cases, supports discontinuation of therapy.Between October, 2013 and October, 2015 five consecutive patients (4 men and 1 woman) were found to have IgG4-related kidney disease in our Unit. Three patients had histologically-proven IgG4-related TIN, while two patients had histologically-proven IgG4-related RPF. Renal and retroperitoneal tissue specimens were examined by light microscopy and immunohistochemistry.et al. [Diagnosis of IgG4-related TIN was based on Raissian's criteria , while het al. .A previous diagnosis of Sjogren-like syndrome had been made in patient #1, who was treated with small doses of oral prednisone. One year later, he was admitted to our Division for rapidly progressive renal failure. Renal biopsy showed an IgG4-related TIN.Patient #2 had been mono-nephrectomized in another hospital due to a suspected neoplasm with a final histological diagnosis of xanthogranulomatous pyelonephritis 16 months before coming to our observation. He was admitted to our Division for rapidly progressive renal failure and underwent renal biopsy, which showed a typical IgG4-related TIN.Patient #3 had undergone colon resection 20 years earlier due to a malignant tumour. He was admitted to our Division for acute renal failure overlapping chronic impairment. Renal biopsy showed an IgG4-related TIN.Patient #4, who had been admitted for lower back pain and mild acute renal failure, showed bilateral hydroureteronephrosis due to retroperitoneal and periaortic abnormal tissue observed both at ultrasound and CT imaging. He underwent an exploratory laparotomy, and the tissue specimen showed features of IgG4-related RPF.Patient #5 underwent radical hysteroannessiectomy 10 months earlier due to suspected uterine cancer with secondary, initially monolateral, hydroureteronephrosis. She required bilateral ureteral stent placement for recurrent hydronephrosis due to the presence of abnormal pelvic and periureteral tissue, characterized by high metabolic activity at the FDG-PET/CT. After admission to our Unit, re-examination of the surgical specimen confirmed the suspicion of histologically active IgG4-related RPF.+ cells and circulating Tregs were measured at baseline and during follow-up in all patients.Estimated GFR using the CKD-EPI formula, blood count, IgG/IgG4, C3/C4, CD20Contrast-enhanced CT or MRI and FDG-PET/CT were performed at baseline and during follow-up in both patients with RPF.Percutaneous needle biopsy was repeated in all the patients with TIN one year after the initial histological diagnosis.Renal samples were obtained by real-time ultrasound-guided percutaneous needle biopsy in patients #1, #2, and #3. Periaortic tissue was obtained by open biopsy of the mass lesion in patient #4 and by surgical hysteroannessiectomy in patient #5. Renal and periaortic tissue specimens were processed for light and immunofluorescence microscopy. Immunostaining was performed using anti-IgG and anti-IgG4 antibodies.plus 2 pulses of 500–750 mg cyclophosphamide (on days 1 and 15) plus 4 weekly Rituximab administrations (375 mg/m2). Two more doses of Rituximab were administered 1 and 2 months following the last weekly infusion.Patients #1, #2, #4 and #5 were treated according to the IBCDT protocol previously described by our group in severe cases of SLE with nephritis . They inIn patient #3 cyclophosphamide was avoided due to his past history of colon cancer.Patients #2 and #5 received isoniazid prophylaxis due to a positive QuantiFERON-TB Gold test result.IgG4-RKD may be a progressive disease that, if untreated, can lead to chronic renal failure and dialysis. Steroid treatment may be insufficient in the most severe forms of IgG4-TIN showing severe tubular atrophy and interstitial fibrosis as well as in cases of IgG4-RPF with widespread involvement. Furthermore its use is limited by several adverse effects, particularly in elderly patients.In our small sample of patients with aggressive disease, IBCDT has proved to be effective and safe. These preliminary observations warrant future studies.


Escherichia coli (CREC) is becoming a serious problem in Chinese hospitals, however, the data on this is scarce. Therefore, we investigate the risk factors for healthcare-associated CREC infection and study the incidence, antibiotic resistance and medical costs of CREC infections in our hospital.The emergence and spread of Carbapenem-resistant We conducted a retrospective, matched case–control–control, parallel study in a tertiary teaching hospital. Patients admitted between January 2012 and December 2015 were included in this study. For patients with healthcare-associated CREC infection, two matched subject groups were created; one group with healthcare-associated CSEC infection and the other group without infection.p = 0.00), medical examination costs (p = 0.00), medical test costs (p = 0.00), total drug costs (p = 0.00) and ant-infective drug costs (p = 0.00) for the CREC group were significantly higher than those for the no infection group. Medical examination costs (p = 0.03), total drug costs (p = 0.03), and anti-infective drug costs (p = 0.01) for the CREC group were significantly higher than for the CSEC group. Mortality in CREC group was significantly higher than the CSEC group (p = 0.01) and no infection group (p = 0.01).Multivariate conditional logistic regression analysis demonstrated that prior hospital stay (<6 months) , tracheostomy , central venous catheter insertion , carbapenem exposure , urinary system disease , low hemoglobin , and high blood glucose are associated  with CREC infection. Total costs (Many factors were discovered for acquisition of healthcare-associated CREC infection. CREC isolates were resistant to most antibiotics, and had some association with high financial burden and increased mortality. Escherichia coli (CREC), as one class of CRE, has become a major threat in hospitals worldwide [E.coli is an emerging problem that is mainly caused by plasmid-encoded carbapenemases [Carbapenems have long served as reliable and potent agents against Gram-negative bacilli . Carbapeorldwide –7. Carbaenemases –13. As aenemases , antimicenemases .There are several previous studies on the risk factors for CRE infection , 17, butThe case–control–control study design of this study, which utilizes two separate case–control analyses, has become a standard method for the specific identification of risk factors that are uniquely connected to infection by antimicrobial-resistant pathogens , 19. We We conducted a retrospective, parallel, case–control–control study to identify the incidence, risk factors, antibiotic resistance, and medical costs associated with the acquisition of healthcare-associated CREC infection among hospitalized patients treated at Xiangya Hospital, a 3500-bed general hospital in Changsha, Hunan Province, Central South China. The CREC infection group was compared with a no infection group to assess the risk factors for acquisition of CREC infection; meanwhile, the CREC group was compared with the CSEC infection group to evaluate reasons for antibiotic resistance.Subjects with CREC or CSEC isolated from multiple sites, or on multiple dates, were counted only once, and the data from the first infection was included in the study. Healthcare-acquired CREC or CSEC infection was defined as isolation 48 hours after admission to the hospital. Healthcare-associated infection (HAI) was defined according to the CDC/NHSN surveillance criteria in patients with samples from any specimen source site positive for CR-EC or CS-EC; meanwhile, the patients with CR-EC or CS-EC colonization and community-associated infection (CAI) were ruled out.Patients from whom CREC were isolated from clinical cultures from any source between January 1, 2012 and December 31, 2015 were included in this study. For each CREC patient, we randomly selected two controls from hospitalized patients who were admitted within the same period with CSEC isolated, and the two groups were matched for age and sex. Additionally, we selected two controls from the in-patients admitted within the study period with no bacterial infection, and the two groups were matched for age and sex.E.coli resistant to at least one of the carbapenems .An automated broth microdilution method  was used to perform identification and susceptibility testing. Carbapenem resistance was determined using the disk diffusion method. All isolates with resistance, or intermediate susceptibility to carbapenem were defined as resistant isolates. Clinical and Laboratory Standards Institute document M100-S22 (January 2012) was used for interpretation of the antimicrobial susceptibility testing and ESBL testing, and CREC was defined as Using current EUCAST breakpoints, imipenem MICs of CR-KP isolates ranged from 2 to >32 μg/ml (breakpoint for resistance and intermediate susceptibility MIC ≥ 2 μg/ml); meropenem MICs from 4 to > 32 μg/ml (breakpoint for resistance and intermediate susceptibility MIC ≥ 4 μg/ml); all the isolates had ertapenem MICs in the resistant range (breakpoint for resistance and intermediate susceptibility MIC ≥ 1 μg/ml).E.coli infection); length of hospital, intensive care unit (ICU) stay before E.coli infection; specimen source site ; invasive procedures  within 1 month prior to E.coli infection; surgical procedures within 1 month prior to E.coli infection; administration of drugs (glucocorticoids and immunosuppressive agents), radiotherapy and chemotherapy within 1 month prior to E.coli infection; specific co-morbidities included many system diseases ; exposure  to antimicrobials  within 3 months prior to CREC identification.Data were obtained from patients’ medical records, and relative data were recorded on structured abstraction forms. Variables analyzed as possible predictors included demographics ; clinical departments where strains were isolated; and the history of admission before the infection .A two-tailed During the 4-year study period, CREC was isolated from 49 patients who met the criteria for healthcare-associated infection (HAI), including fourteen patients in 2012 , seventeen patients in 2013 , eight patients in 2014 , and ten patients in 2015 . The incidence of CREC infection over the 4-year study presented in Fig. A total of 49 patients were included in the case group. CREC was most frequently recovered from respiratory secretions 28.6%), followed by urine (24.5%), surgical wounds (20.4%), blood (12.2%), ascitic fluid (12.2%), and bile (2.0%) (Fig. 8.6%, folThe antibiotic susceptibility patterns of the isolates from the case and control patients are shown in Table Results of the univariate and multivariate analyses from the comparison of the CREC and CSEC groups regarding the risk factors for healthcare-acquired CREC are shown in Table The univariate and multivariate analyses results of the CREC and no infection groups are presented in Table Comparison of the CREC and CSEC groups, and the CREC and no infection groups, in terms of economic costs are shown in Table To our knowledge, few studies have evaluated the risk factors for the acquisition of CREC infection. Therefore, the aim of our matched case–control–control study was to assess the potential risk factors  for the During our study period, the incidence of CREC infection was lower than 1/10,000 patient days; it was likely related to the presence of active antimicrobial stewardship teams in the hospital. Although the incidence of CREC is low in CRE, carbapenem resistance in Escherichia coli is also emerging worldwide; the reasons for the spread of CREC are likely limited infection control and antimicrobial control measures .The CREC strains were resistant to at least three kind of antibiotics, the antibiotic resistance of the CREC group was more severe than that of the CSEC group. Compared with the strains from the CSEC patients, most of those from the CREC patients were resistant to cephalosporins, penicillin, aztreonam, ciprofloxacin, and levofloxacin, but the strains remained relatively susceptible to amikacin and nitrofurantoin. We could not have chosen a better way to treat CREC infections considering the above results and according to individual clinical conditions.The results of our study show that the CREC group was associated with more expenses than the other two groups, particularly in terms of the medical examination costs, total drug costs, and anti-infective drug costs; thus, it appears that antibiotic resistance associated with a higher financial burden. The result is consistent with the study of Bartsch et al. . In our In our study, the univariate analyses of the two case–control groups found many common risk factors, including prior hospital stay, invasive procedures such as urinary catheter insertion , incisioThe identification of prior hospital stay as risk factor is not unexpected . The envFrom these two comparisons, it is not surprising to find that invasive procedures, including urinary catheter insertion , incisioThere is a close association between healthcare-associated infection and antibiotic use –33, espeIt is interesting that the related laboratory results including low hemoglobin and high blood glucose are risk factors for CREC infection, which is different from other studies. The low hemoglobin and high blood glucose are susceptibility risk factors for infection; therefore, special attention should be paid to patients that meet these criteria. We can closely monitor the infection index of these patients while reducing the exposure to risk factors for infection.One limitation of our study is that we could not assess the patient-to-patient infection spread, we did not collect isolates for gene molecular epidemiologic analysis, thus, we could not assess if there were any outbreaks during the study period. The second is the small study sample size. Moreover, the financial burden is associated with total cost of patients after isolation of CREC or CSEC, of which the direct cost of CREC or CSEC infection was not considered.Our results suggest that healthcare-acquired CREC infection may be related to prior hospital stay, tracheostomy, central venous catheter insertion, carbapenem exposure, and urinary system disease. Further, anemia and high blood glucose are important risk factors for the acquisition of CREC infection. Hospital infection control and the implementation of antimicrobial stewardship practices across the continuum of healthcare settings will hopefully help to curb the emergence and spread of CREC infections.


The present study concerns compressive and flexural constitutive models incorporated into an isoparametric beam finite element scheme for fiber reinforced polymer (FRP) and concrete composites, using their multi-axial constitutive behavior. The constitutive behavior of concrete was treated in triaxial stress states as an orthotropic hypoelasticity-based formulation to determine the confinement effect of concrete from a three-dimensional failure surface in triaxial stress states. The constitutive behavior of the FRP composite was formulated from the two-dimensional classical lamination theory. To predict the flexural behavior of circular cross-section with FRP sheet and concrete composite, a layered discretization of cross-sections was incorporated into nonlinear isoparametric beam finite elements. The predicted constitutive behavior was validated by a comparison to available experimental results in the compressive and flexural beam loading test. As already well known, fiber reinforced polymer (FRP) manufactured by glass or carbon fiber improves concrete properties, in particular, the strength and ductility arising from enhanced confinement of the structural members ,6,7,8,9.et al. (1988), is often refined to interpret the concrete-filled composites [et al. (2001) additionally developed a model using an equivalent tangent modulus determined from the total lateral strain [A confinement model proposed by Mander mposites ,10, as tl strain . Propertl strain .The present study concerns a development of the nonlinear material model for multi-axial constitutive behaviors to predict the compressive and flexural behaviors of FRP sheet and concrete composites. The constitutive model was developed by the basic concept of an isoparametric beam finite element in the present study. Concrete is regarded as an orthotropic material described by the hypoelasticity-based principle in triaxial constitutive law. Simultaneously, the principal stress direction is assumed to be parallel to the orthotropic directions. In defining the confinement effect, a three dimensional failure surface in the current concrete triaxial stress state was formulated together with behavior of the FRP sheet, being based on the two-dimensional lamination theory for composite laminated materials. To predict the flexural behavior of circular cross-section with FRP sheet and concrete composite, a layered discretization of cross-sections was employed, considering nonlinear isoparametric beam finite elements. After cracking of concrete, the effect of tension stiffening due to the presence of the FRP jacket is also taken into account. Finally, the constitutive model was verified by a comparison to experimental results of compressive and flexural beam loading test.i.e., 1, 2 and 3) and in the structure coordinate  can be respectively expressed, as follows:T indicates the transformation matrix; the σ and ε are for the stress and strain vectors in the local coordinate , respectively; while the σ and ε1 are for the stress and strain vectors in the structure coordinate , respectively. Simultaneously, the coefficients of the constitutive matrix Q can be rendered as follows:E1 is for the modulus of the lamina in the fiber direction; E2 for the modulus normal to the fiber direction;G12 for the in-plane shear modulus of the lamina.A single lamina of the FRP sheet consists of unidirectional fibers embedded in the matrix, which is taken as a transversely isotropic material in modelling the plane normal to the fiber direction, as seen in x, y, and z).From the constitutive equation for a single lamina, the in-plane stress-strain relation of a laminated composite can be an equivalent orthotropic composite material in the coordinate dσir; the increment of longitudinal stress in the FRP composite, dσL; and the increment of radial strain in concrete, dεr;, can be derived, respectivelyThe compatibility in the cross-section should be satisfied as shown in r and σr = σh. In the test of confined concrete, it is known that the radial and hoop stresses of concrete were mostly identical and thus the assumption has been commonly adopted in the majority of previous studies [As the behavior of concrete wrapped by a FRP jacket is triaxial rather than uniaxial, a triaxial constitutive model is required. To determine the tri-axial strength of confined concrete wrapped by FRP composite, as shown in  studies ,3,10.ciε' in the equivalent uniaxial stress and strain curve of concrete as shown in A strain surface is required to define the peak compressive strain, The layered cross-sectional discretization, as shown in D is the section force vector consisting of section moments; di for the section deformation vector consisted of section curvature; iy for the displacement fields at the ith Newton-Raphson iteration; and f for the section flexibility matrix, respectively. By the principle of virtual work, the equilibrium can be formulated in relation of the section deformation vector, d = ∂yd is the virtual section deformation vector caused by the virtual displacement δy; Q and q for the nodal force and nodal displacement vectors, respectively; while p for the applied load vector per unit length. The Hellinger-Reissner mixed formulation can be derived by a combination of the compatibility and equilibrium equations as:The weak form of the compatibility conditions can be derived by applying a statically admissible virtual force system asD are interpolated in terms of the force degrees of freedom Q. Also the displacement fields y are interpolated in terms of the nodal displacements q.To make it feasible the variational expression of equilibrium relation in a finite element approach, it must be discretized in terms of nodal quantities. In a mixed finite element formulation, the internal forces Ki−1 is the element stiffness matrix at the end of the last iteration defined as follows:b and a are the interpolation functions for the internal forces and the element displacements, respectively; while eP and riq−1 for the equivalent nodal load and nodal residual vectors, respectively; Qri−1 is the element resisting forces defined asBy applying the interpolation of internal forces and displacement fields, the function of the mixed finite element formulation can be obtained asTo compute the sectional force vector and flexibility matrix, corresponding to the section deformation in the element formulation, each cross-section relies on the layered cross-sectional discretization as seen in A comparison of the available experimental tests to the analysis result, predicted by the current model in chapter 2, was performed. The two series of experimental tests involving axially loaded FRP and concrete composite cylinders were investigated in this section. A compression test for the CFRP and concrete composite cylinder was taken with a cylindrical specimen of 152.0 mm diameter , as showi.e., 0.338 mm and 0.676 mm, respectively). The fiber tensile strengths of the two specimens accounted for 2810 MPa and 2327 MPa, respectively. Simultaneously, the elastic modulus of the CFRP layer was 439 MPa along the fiber direction, while the uniaxial unconfined concrete strength was 39 MPa. For the specimen of the CFRP thickness of 0.676 mm, as shown in The compression test of CFRP and concrete cylinders with 200 mm in the diameter and 600 mm in the height was also confirmed by the prediction obtained from the proposed model . Two speThe four-point bending test of a CFRP and concrete composite beam  was takeThe axial and hoop strains of the top and bottom fiber of the cross-section in the center span were presented in The compressive and flexural constitutive behavior of a FRP sheet and concrete composite was formulated from their multiaxial constitutive laws and the material constitutive models, incorporating into an isoparametric mixed beam finite element scheme with the circular cross-section of the beam. The nonlinear local cross-sectional strains both in axial and lateral directions was predicted by the model developed in the present study, and then the confining behavior of concrete was rationally estimated when wrapped by FRP composite sheet.In a comparison of the analysis to the experiment on the compressive cylinder test and bending load test to beams, the compressive behavior of CFRP sheet and concrete composite cylinder was well predicted. Also the overall transverse load and displacement response of the beam indicated a positive consistent result. Additionally, a comparison of the model for the axial and hoop responses in CFRP sheet and concrete composite sections to the experiment was taken to estimate the expansion of crushed concrete at ultimate load level.


Dear Editor,Epigenetic factors, acting as co-activators/repressors in transcription, regulate diverse cellular activities ranging from cell growth and differentiation to host defense and immune response. Covalent histone or DNA modifications, histone variants, ATP-dependent chromatin remodeling, and non-coding RNA are major mechanisms underlying epigenetic regulation. In particular, ATP-dependent chromatin remodeling complexes and histone chaperones are key factors that regulate chromatin dynamics.Death domain-associated protein (DAXX), originally identified as a Fas death receptor binding protein during apoptosis, was characterized as an H3.3-specific histone chaperone to promote replication-independent deposition of H3.3  syndrome  and the DAXX interaction domain of ATRX   Fig. .ATRX essential for DAXX interaction, we generated a series of DIDATRX truncations based on secondary structural analysis, and performed isothermal titration calorimetry (ITC) studies  of 4.5 μmol/L between full length DIDATRX  and DHBDAXX. Strikingly, we detected a binding KD of 70 nmol/L between a 42-residue segment of DIDATRX and DHBDAXX. This segment is characteristic of a loop-helix motif and spans residues 1,244–1,285 of ATRX  was used for ITC titration, stressing the role of loop ATRX1,244–1,264 in promoting DAXX-ATRX interaction.To further map the minimal region of DIDies Fig. B. We meaDAXX-ATRX1,244–1,285, and solved the crystal structure at 1.58 Å by zinc single wavelength anomalous dispersion (Table S1). Full length DHBDAXX and residues 1,256–1,285 of ATRX were modelled based on the electron density map . DHBDAXX features a core four-helical bundle and ATRX1,256–1,285 adopts a loop-helix fold that targets the “α2-α5” surface of DHBDAXX . Despite extensive interactions, our SEC-MALS (size exclusion chromatography followed by multi-angle light scattering) analysis suggested that the DHBDAXX-ATRX1,244–1,285 complex exists as a monomer in solution and the observed dimer formation is likely due to crystal packing . The free and complex states of DHBDAXX are well superimposable without clear conformational change , suggesting that the ATRX binding surface of DHBDAXX is largely preformed. Since only ATRX1,259–1,285 is visible in the complex structure, we next tested if this short motif is sufficient for DAXX binding. A binding KD of 70 nmol/L was measured between ATRX1,259–1,285 and DHBDAXX   of different concentration, and then subjected to native-PAGE analysis. As shown in Fig. DAXX and ATRX form a complex in promyelocytic leukemia (PML) nuclear bodies and heterochromatin to regulate gene activity and chromatin structure. DAXX recruits Rassf1C into PML nuclear bodies and releases it when DAXX is degraded upon DNA damage Below is the link to the electronic supplementary material.


There is little evidence regarding the effectiveness of intervention methods in the treatment of zoster-related pain (ZAP) after the acute phase of zoster. Generally, if ZAP remains after more than 180 days from its onset, the likelihood of pain reduction is very low; this condition is considered as a “well established” post-herpetic neuralgia (PHN). Although the clinical efficacy of intrathecal steroid injection and spinal cord stimulation (SCS) for ZAP management has been reported, these interventions are not widely used due to inherent disadvantages. Continuous epidural block is widely used in clinical practice, and the effectiveness of pulsed radiofrequency (PRF) to the dorsal root ganglion (DRG) in the treatment of ZAP already has been reported.The purpose of this study was to compare the clinical efficacy of continuous epidural block and DRG PRF beyond acute phase of zoster, bur before PHN was well established (from 30 days to180 days after zoster onset).Retrospective comparative study.A total of 42 medical records were analyzed. Patients were divided into two groups according to the type of procedure utilized: continuous epidural block  and DRG PRF (PRF group). The clinical efficacy of the procedure was evaluated using a numeric rating scale (NRS) and the medication dose before and 1 to 6 months after the procedure.There was a significant decrease in the NRS value with time in both groups. However, this decrease was more significant in the PRF group than in the continuous epidural group. The medication doses decreased significantly in the PRF group over time, but not in the continuous epidural group. The rate of clinically meaningful PHN (NRS≥3) was also lower in the PRF group than in the continuous epidural group.This study revealed that DRG PRF was more effective than a continuous epidural block in treating ZAP after the acute phase of zoster. A neuromodulation method such as DRG PRF may be a useful option for reducing the progression of neuropathic changes caused by the persistent transmission of a pain signal after the acute phase of zoster. Herpes zoster is an infectious disease caused by reactivation of latent varicella zoster virus (VZV), with a lifetime incidence of 30% . Post-heThe acute phase of herpes zoster is usually defined within 30 days after onset of the rash, and various nerve blocks including epidural block are used in the acute stage to prevent PHN ; favorabThe presence of zoster-associated pain (ZAP) in spite of various nerve blocks during the acute phase of herpes zoster can be a challenge to pain physicians. In addition, few interventions for managing pain in the PHN period are supported by evidence ,11.The exact discriminative time point for PHN has not yet been standardized. Various criteria have been used, from 30 days to 180 days after zoster onset. If pain persists for more than 180 days after zoster onset, the likelihood of pain reduction is very low and such a condition is considered "well established" PHN . TherefoIntrathecal steroid injection or spinal cord stimulation (SCS) has been reported to be effective for ZAP control. However, there are also concerns about the risk of potential complications and high medical costs associated with each procedure, respectively. Therefore, it would be beneficial to find an intervention method that can be easily and safely applied in clinical practice.Continuous epidural block is often used in clinical practice in cases where pain is refractory to conservative treatment. The usefulness of repetitive epidural block using an indwelling catheter in acute herpes zoster has been reported , as wellPulsed radiofrequency (PRF) is a variant of thermal radiofrequency that applies pulsed current to limit heat generation to less than 42°C ,16, creaPRF also has been reported to be useful in controlling pain during PHN and herpes zoster –24. In pAlthough continuous epidural block is often used for ZAP management when pain persists after the acute phase of zoster in clinical practice, and DRG PRF was also reported to be useful for ZAP control in PHN or subacute herpes zoster, the clinical effects of these procedures in ZAP management after the acute phase of zoster have not been compared.We retrospectively compared the efficacy of continuous epidural block and DRG PRF for ZAP management beyond the acute phase of zoster, but before PHN was well established (between 30 and 180 days after zoster onset).We analyzed the medical records of patients who underwent continuous epidural block or DRG PRF to manage ZAP from January 2010 to September 2016. In this analysis, only the medical records of patients who underwent the procedure between 30 and 180 days after zoster onset were included. We classified patients with continuous epidural block as the continuous epidural group and those with DRG PRF as the PRF group.Trigeminal-nerve-involved zoster or follow-up loss within 6 months after the procedure was excluded from the analysis. We also excluded those who did not receive appropriate antiviral treatment during the acute phase of herpes zoster. To accurately compare the effects of the two procedures, we excluded cases where both procedures were performed between 30 and 180 days of zoster onset.This retrospective analysis was approved by the Institutional Ethics Committee of Daejeon St. Mary’s Hospital, Republic of Korea (DC17RESI0027).After placing the patient in the prone position, an 18-gauge Tuohy needle was introduced into the interlaminar space at the second or third level below the target level under fluoroscopic guidance.The epidural space was confirmed using the loss of resistance (LOR) technique; then a 20- gauge epidural catheter was inserted through the Tuohy needle and placed at the target level .After confirming the position of the catheter tip, 0.187% ropivacaine was infused at a rate of 1 ml per hour. Ropivacaine concentration and rate of administration were adjusted by the degree of pain relief or side effects. When appropriate pain relief was achieved, the catheter was removed. The period of catheterization was limited to within 2 weeks, due to concerns regarding infection.The patient was placed in the prone position and the fluoroscopy was slightly rotated to the lesion side. A 22-gauge, 10-cm electrode with a 10-mm active tip  was placed near the target DRG under fluoroscopic guidance.The needle tip was placed under the pedicle in the anteroposterior view and in the posterocranial portion of the intervertebral foramen in the lateral view for fluoroscopic imaging .Sensory stimulation was performed using a 50-Hz current. If a tingling sensation was observed in the affected dermatome below 0.5 V, the position of the needle was considered appropriate.After confirming the needle position, PRF of 42ºC  was applied for 360 seconds. Impedance was maintained at less than 500 Ω throughout the procedure.The following data were collected and analyzed: sex, age, involved dermatome, days from zoster onset to the procedure, types of procedures performed during acute herpes zoster, numerical rating scale (NRS) before the procedure, NRS 1 to 6 months after the procedure, and doses of anticonvulsants and analgesics before and 1 to 6 months after the procedure.We also investigated whether an additional nerve block was performed during the 6-month follow-up period after each procedure.The analgesic effect of each procedure was assessed by the NRS, as well as the dose of anticonvulsants and analgesics. The NRS and dose of anticonvulsants and analgesics were compared between groups both before the procedure, and 1 to 6 months after the procedure.For ease of analysis, anticonvulsant doses were converted to pregabalin-equivalent doses ,26 and aIn various studies, clinically meaningful PHN was defined as persistent pain with an intensity of three points or more on the NRS –30. In tData normality was evaluated using the Kolmogorov-Smirnov test. The Mann-Whitney U test or the independent t-test was used to compare the outcomes between the groups for continuous variables. Data are presented as mean ± standard deviation (SD) for continuous variables. For categorical variables, the Chi-square test or Fisher’s exact test was used.p values of <0.05 were considered statistically significant.Repeated measures analysis of variance was used to assess of the alterations in pain medication doses after the procedure over time. All data were analyzed using SPSS version 18.0 , and A total of 52 patient medical records were reviewed; of these, 9 patients were lost to follow-up before 6 months following the procedure. One patient underwent both continuous epidural block and DRG PRF between 30 and 180 days of zoster onset; the medical record of this patient was excluded from the analysis. In summary, the medical records of 42 patients were used for the analysis. Among them, 22 patients underwent continuous epidural block  and another 20 patients underwent DRG PRF (PRF group) .Age, sex, level of involved dermatome, and presence of underlying disease were not significantly different between the two groups. There were also no significant differences between the groups in pre-procedure NRS, dose of medication before the procedure, and types of intervention during the acute herpes zoster phase .The mean duration of catheter implantation in the continuous epidural group was 11.182±3.142 days, and the mean concentration of ropivacaine and infusion rates used were 0.224±0.07% and 1.818±0.646 ml/hr, respectively.p = 0.029). NRS values were significantly lower in the PRF group from 1 month to 3 months and 6 months after the procedure than those in the continuous epidural group  was significantly higher in the continuous epidural group at intervals of 1, 3 and 6 months .There was no significant difference in analgesic dose between the two groups. However, in the PRF group, there was a significant decrease in dose in the first month after the procedure compared to the pre-procedure dose, while there were no significant changes at all time points compared to pre-procedure in the continuous epidural group .p = 0.042). In the PRF group, there was a significant decrease in anticonvulsant dose at intervals of 4, 5 and 6 months compared to the pre-procedure dose, while in the continuous epidural group, it was significantly increased until 3 months after the procedure .The proportion of patients requiring additional nerve blocks for ZAP control after continuous epidural block or DRG PRF was lower in the PRF group than in the continuous epidural group; however, this difference was not statistically significant .There were no serious complications associated with the procedure in either group. However, 36.3% (8/22) of patients in the continuous epidural group showed evidence of mild complications,including catheter insertion site pain, headache, dizziness, dysuria, constipation, and motor weakness. In the case of one patient, the continuous epidural block was discontinued due to severe pain at the catheter insertion site. In contrast, in the PRF group, only one patient complained of pain at the procedure site, and it improved within a few days. This difference in the incidence of complications between the groups was significant  was also lower in the PRF group.Significant shortening of ZAP duration in continuous epidural block in acute herpes zoster has been reported . Even afThis study was the first to analyze the results of a continuous epidural block applied after the acute period of herpes zoster; however, the clinical results of the continuous epidural group were unsatisfactory compared to the PRF group.We started infusion with a low concentration of 0.187% ropivacaine, which is a relatively low concentration of local anesthetic compared to that utilized in other studies. This low concentration of local anesthetic may be the origin of the inferior outcomes of continuous epidural block in this analysis. However, it has been reported that the concentration of local anesthetic required to inhibit ectopic discharge from a damaged nerve is lower than the concentration required to block normal nerve conduction , 33.Moreover, the most common zoster-affected levels are thoracic dermatomes, and patients who undergo continuous epidural block to control ZAP are usually elderly. In these patients, persistent high rates of infusion and high concentrations of local anesthetic administered over several days may lead to extensive hemodynamic changes, and these changes can be particularly dangerous in the elderly. Therefore this can be a barrier to increasing the concentration and infusion rate of local anesthetics.On the other hand, DRG PRF may have a relatively lower risk of hemodynamic changes than continuous epidural block. Although the exact mechanism of the analgesic effect of PRF has not been fully elucidated, recent studies have reported increases in c-fos expression , 35, eviIn the present study, the decrease in the NRS value was greater in the PRF group than in the continuous epidural group, and doses of anticonvulsants and analgesics tended to decrease with time in the PRF group, while this tendency was not found in the continuous epidural group. These results may support the long-term effects of PRF.Spinal cord stimulation (SCS) is also a representative method of neuromodulation. The usefulness of SCS in the treatment of subacute herpes zoster or PHN has been reported . HoweverAlthough intrathecal steroid injection has been reported to be effective during the PHN period , the cliBecause of concerns associated with SCS and intrathecal steroid injection, these procedures are unlikely to become standard treatments for PHN or subacute herpes zoster. Continuous epidural block also poses the risk of infection due to the presence of an indwelling catheter. Moreover, epidural catheterization generally requires hospitalization.In contrast, DRG PRF is less likely to cause a fatal infection than the above-mentioned procedures, and can easily be performed in an outpatient clinic setting without hospitalization. In the present analysis, the incidence of mild complications was significantly lower in the PRF group than in the continuous epidural group.This was a retrospective study based on the analysis of medical records, and medication data relied on prescription records. In many cases, patients reported self-tapering of medication due to reduced pain. Therefore, there may be a difference between the actual dose taken and the prescribed medication dose, which, together with the small sample size, may be a limitation of the present study.Additionally, since this study was a retrospective analysis, we could not standardize the medications. Because of this, it is possible that there was a statistical error in the comparison of medication doses between groups.The absence of a "no-procedural" control group can also weaken the conclusions of the presentanalysis, which is another limitation of our study.In conclusion, the PRF group showed a significant decrease in ZAP over time compared with the continuous epidural block group, and the rate of clinically meaningful PHN in the PRF group was significantly lower than that in the continuous epidural block group. This is the first study to compare the clinical outcomes of different intervention methods applied in the period following the acute phase of herpes zoster. Based on these results, in cases with progressive neuropathic changes such as those following the acute stage of herpes zoster,a neuromodulation modality such as DRG PRF may be more effective for pain management than continuous blockade of nociceptive input.Further well-controlled, prospective trials with appropriate sample sizes are needed to confirm these findings.S1 File(XLSX)Click here for additional data file.


Within this paper, the assessment of tension stiffening effects on a reinforced concrete element with circular section subjected to axial and bending loads is presented. To this purpose, an enhancement of an analytical model already present within the actual technical literature is proposed. The accuracy of the enhanced method is assessed by comparing the experimental results carried out in past research and the numerical ones obtained by the model. Finally, a parametric study is executed in order to study the influence of axial compressive force on the flexural stiffness of reinforced concrete elements that are characterized by a circular section, comparing the secant stiffness evaluated at yielding and at maximum resistance, considering and not considering the effects of tension stiffness. Reinforced concrete elements are characterized—even for low force values—by nonlinear behavior, mainly due to the stress–strain relationship of the two forming materials: concrete and steel. The exact modeling of such behavior can prove to be a very hard issue, and for this reason, several simplifications are usually adopted in order to take into account only the most relevant nonlinear aspects affecting the particular studied problem.However, the low tensile strength of the concrete can be indicated as the most influencing nonlinearity source. The idea of the composite material “reinforced concrete” (r.c.) itself was originally developed to overcome such a limitation of the concrete. The low tensile strength does not influence so much the ultimate resistance of a reinforced concrete element. On the contrary, it can modify the element stiffness also for a high value of the external force due to the "tension stiffening". Tension stiffening can be defined as the phenomenon leading to an increase in the stiffness of a concrete section due to the transmission of stresses from the reinforcing bar to the boundary concrete in the tension between two adjacent cracks .The way of modeling this phenomenon is currently codified by different standards, and several studies have been carried out in the last decade.1 and α2 are the corresponding values computed in the uncracked and fully cracked sections, respectively; ζ is the distribution coefficient, β is a factor that takes into account long term effects ; Sσ is the stress in the reinforcement in tension calculated on the cracked section; and σSF is the evaluated stress under the loading conditions causing first cracking. Eurocode 2 [rm:−s is the mean value of the reinforcing bars’ diameter;Φ−1 is a coefficient that takes into account the bond properties of bond reinforcement;K−2 is a coefficient that takes into account the distribution of strain (pure tension or bending); andK−p,eff = Ast/Act is the effective reinforcement ratio evaluated as the ratio between the area of the reinforcing bars, Ast, contained within the concrete cross section portion effectively influenced by the bars in the formation of cracks.ρEurocode 2  and CEB-α=ζα2+, (h − x)/3 and h/2, where the meaning of the symbols is well explained by Eurocode 2  defines c,eff = (c + 8.5ϕ), with c being the concrete cover and ϕ the reinforcing bar diameter. Braga et al. [c,eff ≈ 1/4(1 + nρ)bh, with b and h the width and height of the section, respectively, n = Es/Ec, and ρ the ratio of steel reinforcement (As/bh). Castel et al. [c,eff, which is based on a multi-linear stress profile in the full depth of the concrete section between the flexural cracks:Several authors have proposed different expressions for the evaluation of the effective area. Manfredi and Pecce  recommena et al.  studied a et al. , in theil et al.  came up The meaning of the symbols is explained in All of these works deal with the definition of the effective area on rectangular r.c. sections. Very little work has been done on circular sections, even if they represent important elements in the field of r.c. construction. It is in fact sufficient to think about the bridge piers or pile foundations that are realized with circular sections: bridge piers are often realized this way, while pile foundations practically always are. Wiese et al. supplied an expression for the determination of the effective area of symmetrically reinforced circular sections, idealizing the reinforcement as a continuous ring. J. F. Carbonell-Marquez et al.  presenteThe influence of tension stiffening on the global behavior of elements with a circular cross section and subjected to the combined axial–flexural action has not, however, as far as the authors know, been ever quantified. The question of if, or in which conditions, it is necessary to model tension stiffening still remains without clear answers. Moreover, the influence on tension stiffening effects of the axial force, to which circular cross section elements such as bridge piers and pile foundations are usually subjected, or of the reinforcement ratio, has never been quantified.Within the present paper, the modeling approach adopted by Salvatore et al.  for rectb1 is the bond stress in the elastic phase, and τb2 is the bond stress at yielding. The bond and steel tensile stresses, together with the steel tensile strain resulting from the application of an increasing force to the steel bar, are schematically shown in Salvatore et al.  proposedct, for the concrete in tension in the post-cracking phase is defined.To consider the deformational effects consequent to sliding between the steel and the concrete and the consequent redistribution of stresses, a fictitious elasticity modulus, Ect is derived from the equilibrium equation of an infinitesimal length of bar surrounded by the portion of concrete involved in the transmission of stresses from the bar to the concrete itself. On the base of the stress condition of the steel bar, Salvatore et al. [ct:The definition of Ee et al.  derived scr ≤ σs,max < fy:s,min ≤ fy < σs,max and x ≥ xy:y < σs,min or σs,min ≤ fy < σs,max and x < xy:s,min and σs,max are the minimum and maximum stresses in the bar occurring respectively in the midline section and in the cross-sections of the element where the crack forms; σscr is the stress in the steel upon first cracking; and, finally, xy is the distance from the cracked section where the stress in the steel begins to be lower than the yield stress.for σct would be defined by Equation (5), but the following observations can be made:−ct(x), Ect,lim should be at least equal to the elastic modulus of the concrete in compression, Ec.for −ct should be equal to zero (corresponding to the cracked section).for The modelling approach adopted by Salvatore et al.  briefly scr.In ct should respect the following limits:ct,lim represents the likely maximum value of the elasticity modulus in tension, assumed, in the present study, to be equal to the concrete elasticity modulus in compression.It is immediate to understand that, in order to obtain real physical meaning, the fictitious elasticity modulus in tension Escr ≤ σs,max < fy,:For this reason, we assumed, for σct, evaluated by adopting Equation (9) is shown.In A-B, between the two consecutive cracked sections can be so evaluated as follows:A, χλ/4A, χλ/2, χλ/2B, and χB are, with reference to The moment–rotation behavior of the circular cross section portion of an element that is comprised between two consecutive cracks can be obtained by integrating the moment–curvature relationship along the length of the element itself, and adopting for the concrete in tension the fictitious elasticity modulus given by Equations (6), (7), and (9). Alternatively, as assumed in the present study, the element can be discretized in smaller elements, and the curvature considered to be constant within each element. The rotation, ΘTo evaluate the moment–curvature relationship, each section was so discretized into a finite number of longitudinal fibers , distingThe concrete behavior in compression was modeled using the Mander  approachThe displacement of a circular cross section element in bending was then easily estimated, by subdividing it into blocks. The length of each block in the cracked portion of the element was assumed to be equal to the crack’s distance. In the uncracked portion it was assumed to be the maximum block length observed in the cracked zone.tot, was computed by summing the displacements, δi, of each block comprised between the two sections.i, is the length of the i block; N is the number of blocks in which the portion of element is divided into; and Θi is the relative rotation between the two faces of the i block evaluated using Equation (10), as shown in The relative displacement between two sections, ΔThe procedure described in the previous paragraphs was validated by applying it to evaluate the load-deflection curves of several r.c. circular cross section elements, and then comparing them with the experimental results.For this purpose, the experimental tests conducted by Lehman and Moehle  and by CLehman and Moehle  tested aIn both cases, the transverse load was applied cyclically, and with an increasing amplitude. The envelope curve of each test was taken into consideration in order to compare the monotonic experimental behavior with the numerical behaviour. It was also assumed that phenomena such as low cycle fatigue do not influence the response of the column, given the low values of the imposed displacements .The cracks pattern recorded by Lehman and Moehle  and Cald−for column 407, not considering tension stiffening can lead to a sensible error in evaluating the element’s stiffness;−for more slender columns (828 and 1028), tension stiffening effects are more evident than for shorter ones (328 and 328T).Using the bending moment profile M(z) along the column calculated at each loading step, the corresponding deflections were obtained by adopting the procedure described in the previous paragraphs. The numerical curves were evaluated up to the point corresponding to the peak stress in the concrete in compression. The focus of this research is, indeed, to evaluate the influence of tension stiffening on flexural stiffness. So, the behavior of the r.c. elements with circular sections beyond this point was not investigated within this research. The comparison between the experimental and numerical results, as shown in To study the influence of tension stiffening on global behavior, in this section a parametric analysis was performed for different cross sections, varying: the diameter, the longitudinal reinforcing ratio, and the compressive force. The cases considered in the parametric analysis are summarized in The results presented herein were obtained in two ways: one by taking into account the influence of the tension stiffening, and adopting the model proposed in the previous paragraphs; the other by neglecting it. It was so possible to point out how tension stiffening can affect the performance of a reinforced concrete element with a circular section.sec at the first steel bar yielding and the intact flexural rigidity of the section (EcI = EcπD4/64), and the second referring to a normalized moment of inertia defined as the ratio between the secant flexural rigidity evaluated when the concrete reaches peak stress in compression and the intact flexural stiffness.Assuming that the concrete elastic modulus remains constant, the influence of tension stiffening was evaluated in terms of an equivalent moment of inertia. For every diameter considered and listed in −less evident on the secant stiffness at the first bar yielding than on that evaluated at the maximum bending moment;−increasing as the reinforcement ratio decreases;−not so much influenced by the axial force, except for low values of the reinforcement ratio; and−higher for smaller diameters.ct.Within this paper, the influence of tension stiffening on the global behavior of elements with a circular cross section and subjected to the combined axial–flexural action was studied. A preliminary analysis of the modeling approach adopted by Salvatore et al.  was carrThe comparison of numerical results, obtained with the enhanced model, and the experimental ones, provided by the studies of Lehman and Moehle  and Cald−is less evident on the yield stiffness than that of the one evaluated at the moment corresponding to the reaching of peak stress in compression in concrete;−increases as the reinforcement ratio decreases;−is not so much influenced by the axial force, except for low values of the reinforcement ratio; and−is higher for smaller section diameters.The parametric analysis carried out using the enhanced model, and varying the values of the axial force and reinforcement ratio, highlighted that the influence of tension stiffening:These results suggests that for r.c. elements characterized by a circular section with a diameter larger than 1 m and with a reinforcement ratio higher than 1%, such as usual bridge piers, the influence of tension stiffening can be neglected.The influence of tension stiffening becomes sensible for low diameters  and low values of the reinforcement ratio (lower than 1%). However, in general, in the case of foundation piles, it can be easily assumed that the influence of tension stiffening on global behavior is absorbed by the uncertainties in the definition of the soil’s mechanical properties.


The global rise and spread of antibiotic resistance is limiting the usefulness of antibiotics in the prevention and treatment of infectious diseases. The use of antibiotic stewardship programs guided by local data on prescribing practices is a useful strategy to control and reduce antibiotic resistance. Our objective in this study was to determine the prevalence and indications for use of antibiotics at the Korle-Bu Teaching Hospital Accra, Ghana.An antibiotic point prevalence survey was conducted among inpatients of the Korle-Bu Teaching Hospital between February and March 2016. Folders and treatment charts of patients on admission at participating departments were reviewed for antibiotics administered or scheduled to be administered on the day of the survey. Data on indication for use were also collected. Prevalence of antibiotic use was determined by dividing the number of inpatients on antibiotics at the time of survey by the total number of patients on admission.Of the 677 inpatients surveyed, 348  were on treatment with antibiotics. Prevalence was highest among Paediatric surgery where 20/22 patients  were administered antibiotics and lowest among Obstetrics patients with 77/214 . The indications for antibiotic use were 245/611 (40.1%) for community-acquired infections, 205/611 (33.6%) for surgical prophylaxis, 129/611 (21.1%) for healthcare associated infections and 33/611 (5.4%) for medical prophylaxis. The top five antibiotics prescribed in the hospital were metronidazole 107 (17.5%), amoxicillin-clavulinic acid 82 (13.4%), ceftriaxone 17(12.1%), cefuroxime 61 (10.0%), and cloxacillin 52 (8.5%) respectively. Prevalence of meropenem and vancomycin use was 12(2%) and 1 (.2%) respectively. The majority of patients 181 (52%) were being treated with two antibiotics.This study indicated a high prevalence of antibiotic use among inpatients at the Korle-Bu Teaching Hospital. Metronidazole was the most commonly used antibiotic; mainly for surgical prophylaxis. There is the need to further explore factors contributing to the high prevalence of antibiotic use and develop strategies for appropriate antibiotic use in the hospital.The online version of this article (10.1186/s13756-018-0299-z) contains supplementary material, which is available to authorized users. The discovery of antibiotics in the twentieth century immensely changed medical practice. It allowed for treatment of life threatening conditions and the conduct of complex medical procedures with a reduced risk of infections. Over time, global overuse of antibiotics has emerged as a major problem , 2, withExcessive use of antibiotics leads to the development of complications such as antibiotic related diarrhoea and healthcare associated infections , 5. It iContinuous evaluation of antibiotic use is important to preserve the effectiveness of antibiotics and minimize patient harm . The WHOn = 1321 patients per 2000 beds) [The Korle-Bu Teaching Hospital is a 2000-bed tertiary referral hospital situated in Accra, Ghana with about 200 admissions per day . The hosA multidisciplinary team of doctors and an infectious disease specialists conducted the survey at selected units. Training and piloting of the study instrument was conducted for the survey team prior to the start of the study. Briefly, the training session chaired by the lead investigator introduced survey personnel to the objectives of the study; the purpose of each item on the data collection tool including definition of terms and indicator codes; methods for assessment of individual patient data; and the roles and responsibilities of each survey personnel. The session was concluded with a 1-day pilot point-prevalence survey in a Medical ward. This session was conducted a week prior to study inception to allow for corrective action. The point prevalence survey was conducted from 8 am to 8 pm daily within a 2-week period. Data collection from each unit was completed within the 12-h period. The survey team performed retrospective data collection using standardized case report forms which primarily comprise a patient-level structured template for documenting antimicrobial use on the day of survey  for cleaning and analysis. The prevalence of antibiotic use was defined as a percentage of the total number of patients on any systemic antibiotic at the time of survey against the number of patients on admission. Descriptive statistics  were used to examine data on antibiotic use. Proportions were compared using Chi-square tests.n = 214), Child Health (n = 111), Medicine (106), Orthopaedics (n = 84), General Surgery (n = 55), Gynaecology (n = 38), Neurosurgery (n = 23), Urology (n = 24) and Paediatric Surgery (n = 22). The median age of included patients was 39 years and 54.2% were females. Adults (age > 15 years) comprised 71%, followed by children  and neonates .A total 677 in-patient folders were reviewed from participating units/departments. The majority of included patients were admitted at the Obstetrics unit (n = 366/611). They were administered in 32.8% (n = 222/677) of admitted patients. Significantly fewer patients  received oral antibiotics. Across hospital units, the proportion of patients on antibiotics ranged from 36%  in Obstetrics to 90.9%  in Paediatric surgery. Of 348 patients on antibiotics, 127  were on one antibiotic, 181  were on two antibiotics, 38  were on three antibiotics whilst 2  were on 4 antibiotics , nitroimidazoles , 3rd generation cephalosporins , 2nd generation cephalosporins , and aminoglycosides . The five most commonly used generic antibiotics (Table n = 83), ceftriaxone , cefuroxime , and cloxacillin . The obstetrics unit accounted for the highest use of metronidazole  and amoxicillin-clavulanic acid  respectively. Figure Table n = 205) was metronidazole , followed by amoxicillin-clavulanic acid  and cefuroxime . For community-acquired infections, the three commonly prescribed antibiotics were ceftriaxone , cloxacillin and gentamicin . Of the 128 antibiotics used for hospital-acquired infections, the top three drugs were ceftriaxone , metronidazole , and cloxacillin . The proportion of antibiotic use by anatomic site is presented in Table n = 101) of all antibiotic prescriptions were for undefined reasons. The majority of antibiotics were prescribed for genitourinary and obstetric systems , and skin, soft tissue, bones and joints . The three most prescribed antibiotics for the former were metronidazole , amoxicillin- clavulanic acid , and cefuroxime . Clindamycin , cefuroxime  and ciprofloxacin  were the most indicated antibiotics for skin, soft tissue, bones and joints.Overall, 245 (40.1%) of 611 prescriptions were administered for community-acquired infections, 128 (21.0%) for hospital-acquired infections, 205 33.6%) for surgical prophylaxis and 33 (5.4%) for medical prophylaxis  and surgical prophylaxis (33.6%). The prevalence level reported in this study is comparable to a prevalence rate of 53% recorded in a previous study among inpatients at KBTH in 2000 . These rThe prevalence rate is however lower than 59.9% prevalence of antibiotic use recorded among out patients in primary healthcare facilities in Ghana . It is aHigh rates of antibiotic use are usually associated with inappropriate use of antibiotics and the development of antibiotic resistance and healthcare associated infections , 8, 26. Enterobacteriaceae and vancomycin resistant enterococcus. Both pathogens are associated with very poor clinical outcomes [The prevalence of antibiotic use was highest among paediatric surgical patients (90.6%) and lowest among obstetric patients (36.0%). This fact could be explained by the high use of prophylactic antibiotics among paediatric surgical patients. The majority of patients (52%) were on two antibiotics. This is comparable to findings from the survey conducted in 2000, where 42.6% of patients in the hospital were on two antibiotics . A signioutcomes , 32.Streptococcus pneumoniae isolates in Ghana [The majority (40%) of antibiotics were prescribed for community-acquired infections. Community- acquired infections were commonly treated with ceftriaxone (18%), with infections of the respiratory tract being in the majority (32.4%). This reflects a common clinical practice of using ceftriaxone as a first line agent for community-acquired pneumonia. However, only moderate penicillin resistance has been reported among in Ghana , 34. Frein Ghana . The mosin Ghana . It is cin Ghana . High usin Ghana . This main Ghana . This stOur study has some limitations. It is a one site study and results may not be extrapolated to other health facilities. The prevalence of antibiotic use may be under estimated since the survey was not conducted in every unit of the hospital. However, based on 62.5%  bed occuIn this point prevalence survey, we found a high prevalence of antibiotic use among inpatients of the KBTH with a relatively high prevalence among paediatric patients. There is high use of metronidazole and amoxicillin-clavulanic acid and low percentage use of vancomycin and meropenem. Majority of the antibiotics were used treatment of community-acquired infections and surgical prophylaxis. Attempts aimed at reducing antibiotic use in the hospital should be focused on the use of the top five antimicrobial agents as well as antibiotics used for surgical prophylaxis. There is also the need to further explore the factors contributing to the high prevalence of antibiotic use and the changing epidemiology of antibiotic use in the hospital.