Clinical outcome of anterior cruciate ligament reconstruction with modified transtibial and anteromedial portal.

Arthroscopic ACL reconstruction is the current standard care of treatment for anterior cruciate ligament (ACL) injuries. Modified transtibial (mTT) and anteromedial portal (AMP) techniques aim at the anatomical placement of femoral tunnel. Controversy existed in the literature with regard to the outcome of these techniques. Hence, we designed a retrospective comparative study to analyse the clinical and functional outcomes of mTT and AMP techniques. We hypothesized that there would be no difference between the clinical and functional outcomes in mTT and AMP techniques. This retrospective observational study was conducted in consecutive patients who underwent arthroscopic ACL reconstruction using semitendinosus-gracilis (STG) quadrupled graft in our tertiary care centre with a minimum follow-up of two years. Out of 69 patients, 37 had undergone ACL reconstruction by mTT technique and remaining by AMP technique. All the patients were assessed clinically by anterior drawer, Lachman's, pivot shift and single-legged hop test. Lysholm Knee Scoring Scale and International Knee Documentation Committee (IKDC) subjective knee evaluation score were used for the functional status. Knee instability was assessed objectively by KT-1000 arthrometer. There was no statistically significant difference in baseline demographic characteristics between mTT and AMP groups. At the end of 2 years, no statistically significant difference was noted in the anterior drawer and Lachman's test. Though not significant, IKDC scores and Lysholm's scores showed a better outcome in the AMP group when compared to the mTT group. AMP group showed significantly better outcome with KT-1000 arthrometer. Based on the results obtained, we presume that overall both mTT and AMP have similar functional outcome. However, as AMP technique offers significantly improved subjective rotational stability on pivot shift test, better hop limb symmetry index and KT 1000 readings compared to mTT, we suggest AMP over mTT.

MMP-9 Levels and NaOCl Lavage in Randomized Trial on Direct Pulp Capping.

Outcome expectations of direct pulp capping in carious teeth are obscured by a clinically unknown infiltration and breakdown of the dental pulp tissue. Histologic studies showed that this soft tissue breakdown is related to the innate immune system. We hypothesized 1) that a neutrophil biomarker could predict the outcome of direct pulp capping and 2) that using sodium hypochlorite (NaOCl) as a lavage solution to remove necrotized infected pulp tissue could improve it. In this randomized trial in mature posterior teeth causing no or mild discomfort with carious pulpal exposures, pulpal fluid was collected to assess neutrophil gelatinase (matrix metalloproteinase 9 [MMP-9]) per total protein (TP) levels as a predictive local biomarker. Subsequently, the dentin-pulp wound was randomly washed with a 2.5% NaOCl or a physiologic saline solution (1:1 allocation), capped with mineral trioxide aggregate, and the tooth was immediately restored with a resin-based composite restoration. Ninety-six patients were included, and 84 individuals could be followed up to treatment failure or clinically confirmed pulp survival after a minimum of 1 y. The entire data were fitted to a Cox proportional hazards model to assess the influence of the observational variables MMP-9/TP and discomfort with the randomized lavage treatment on pulp survival. The Kaplan-Meier pulp survival rates after 1 y were 55% for saline and 89% for NaOCl lavage. The inflammatory state of the pulp tissue as reflected by MMP-9/TP levels and NaOCl lavage had a highly significant (P < 0.001 and P = 0.004, respectively) impact on pulp survival, while mild preoperative discomfort did not. In conclusion, MMP-9/TP showed great promise as a predictive local biomarker, and NaOCl lavage considerably improved the survival time of cariously exposed and directly capped pulps.

The effect of fascia and free skin graft on the healing of mastoid cavity after canal wall down mastoidectomy.

OBJECTIVE: Post-mastoidectomy delayed cavity healing is a challenge to manage. This study aimed to cut down healing time with a simple technique (fascia with a skin graft) and compared it with controls without this technique. METHOD: The current study was a prospective non-randomised controlled study, conducted in a tertiary referral hospital. Thirty cases and 30 controls with squamosal type chronic otitis media were studied. RESULTS: By the end of first month, 23.3 per cent of cases had healed compared with 3.3 per cent of controls. At the third month follow up, 83.3 per cent of cases and 53.3 per cent of controls had healed. At the sixth month follow up, 93.3 per cent of cases and 86 per cent of controls had healed. CONCLUSION: Healing of the mastoid cavity, as evidenced by epithelialisation and formation of a dry cavity, was faster in cases that received the graft when compared with controls without the graft.

Magnon Modes of Microstates and Microwave-Induced Avalanche in Kagome Artificial Spin Ice with Topological Defects.

We investigate spin dynamics of microstates in artificial spin ice (ASI) in Ni_{81}Fe_{19} nanomagnets arranged in an interconnected kagome lattice using microfocus Brillouin light scattering, broadband ferromagnetic resonance, magnetic force microscopy, x-ray photoemission electron microscopy, and simulations. We experimentally reconfigure microstates in ASI using a 2D vector field protocol and apply microwave-assisted switching to intentionally trigger reversal. Our work is key for the creation of avalanches inside the kagome ASI and reprogrammable magnonics based on ASIs.

Shape-morphing living composites.

This work establishes a means to exploit genetic networks to create living synthetic composites that change shape in response to specific biochemical or physical stimuli. Baker's yeast embedded in a hydrogel forms a responsive material where cellular proliferation leads to a controllable increase in the composite volume of up to 400%. Genetic manipulation of the yeast enables composites where volume change on exposure to l-histidine is 14× higher than volume change when exposed to d-histidine or other amino acids. By encoding an optogenetic switch into the yeast, spatiotemporally controlled shape change is induced with pulses of dim blue light (2.7 mW/cm2). These living, shape-changing materials may enable sensors or medical devices that respond to highly specific cues found within a biological milieu.

Concentration-response studies of the chromosome-damaging effects of topoisomerase II inhibitors determined in vitro using human TK6 cells.

Topoisomerase II (topo II) inhibitors are commonly used as chemotherapy to treat multiple types of cancer, though their use is also associated with the development of therapy related acute leukemias. While the chromosome-damaging effects of etoposide, a topo II poison, have been proposed to act through a threshold mechanism, little is known about the chromosome damaging effects and dose responses for the catalytic inhibitors of the enzyme. The current study was designed to further investigate the potencies and concentration-response relationships of several topoisomerase II inhibitors, including the topoisomerase II poison etoposide, as well as catalytic inhibitors aclarubicin, merbarone, ICRF-154 and ICRF-187 using both a traditional in vitro micronucleus assay as well as a flow-cytometry based version of the assay. Benchmark dose (BMD) analysis was used to identify models that best fit the data and estimate a BMD, in this case the concentration at which a one standard deviation increase above the control frequency would be expected. All of the agents tested were potent in inducing micronuclei in human lymphoblastoid TK6 cells, with significant increases seen at low micromolar, and in the cases of aclarubicin and etoposide, at low nanomolar concentrations. Use of the anti-kinetochore CREST antibody with the microscopy-based assay demonstrated that the vast majority of the micronuclei originated from chromosome breakage. In comparing the two versions of the micronucleus assay, significant increases in micronucleated cells were observed at similar or lower concentrations using the traditional microscopy-based assay. BMD modeling of the data exhibited several advantages and proved to be a valuable alternative for concentration-response analysis, producing points of departure comparable to those derived using traditional no-observed or lowest-observed genotoxic effect level (NOGEL or LOGEL) approaches.

Safety assessment of an etidronate in a sodium hypochlorite solution: randomized double-blind trial.

AIM: To assess whether Dual Rinse HEDP, an etidronate that can be combined with NaOCl to create an endodontic irrigating solution containing both hypochlorite and a chelator in the form of 1-hydroxyethane 1,1-diphosphonic acid (HEDP), alters the clinical efficacy of NaOCl or adds any untoward clinical effects. METHODOLOGY: In this randomized controlled double-blind single-centre trial, a pure NaOCl solution was compared to a HEDP-containing counterpart regarding antimicrobial efficacy, postoperative pain, and the host response by means of changes in MMP-9 levels in periapical fluid. Sixty patients presenting with asymptomatic apical periodontitis (one tooth each) were randomly divided into two groups (N = 30) based on irrigation regime. Pre- and post-treatment microbial aerobic and anaerobic cultures and MMP-9/total protein (TP) periapical fluid samples were collected. Postoperative pain levels were assessed 24 h after treatment. Categorical data were compared between groups using the Fisher's exact test, continuous data using the Wilcoxon signed-rank test, α = 0.05. RESULTS: Irrigation with pure NaOCl rendered 40% canals free of culturable microorganisms, compared to 50% with the NaOCl/HEDP mixture (P = 0.60). As assessed by matrix-assisted laser desorption/ionization-time-of-flight analysis (MALDI-TOF), no apparent selection of aerobic or anaerobic taxa occurred in either group. One patient in the NaOCl group experienced moderate pain, whilst two patients in the NaOCl/HEDP group experienced mild postoperative pain. MMP-9/TP levels in periapical fluid declined significantly (P < 0.001) after 1 week with no medication in the root canal, without significant difference between treatment groups (P > 0.05). CONCLUSIONS: This trial found no influence of HEDP on clinical NaOCl effects.

Seven additional families with spondylocarpotarsal synostosis syndrome with novel biallelic deleterious variants in FLNB.

The location and/or type of variants in FLNB result in a spectrum of osteochondrodysplasias ranging from mild forms, like spondylocarpotarsal synostosis syndrome and Larsen syndrome, to severe perinatal lethal forms, such as atelosteogenesis I and III and Boomerang dysplasia. Spondylocarpotarsal synostosis syndrome is characterized by disproportionate short stature, vertebral anomalies and fusion of carpal and tarsal bones. Biallelic loss-of-function variants in FLNB are known to cause spondylocarpotarsal synostosis syndrome and 9 families and 9 pathogenic variants have been reported so far. We report clinical features of 10 additional patients from 7 families with spondylocarpotarsal synostosis syndrome due to 7 novel deleterious variants in FLNB, thus expanding the clinical and molecular repertoire of spondylocarpotarsal synostosis syndrome. Our report validates key clinical (fused thoracic vertebrae and carpal and tarsal coalition) and molecular (truncating variants in FLNB) characteristics of this condition.

Direct imaging of coexisting ordered and frustrated sublattices in artificial ferromagnetic quasicrystals.

We have used scanning electron microscopy with polarization analysis and photoemission electron microscopy to image the two-dimensional magnetization of permalloy films patterned into Penrose P2 tilings (P2T). The interplay of exchange interactions in asymmetrically coordinated vertices and short-range dipole interactions among connected film segments stabilize magnetically ordered, spatially distinct sublattices that coexist with frustrated sublattices at room temperature. Numerical simulations that include long-range dipole interactions between sublattices agree with images of as-grown P2T samples and predict a magnetically ordered ground state for a two-dimensional quasicrystal lattice of classical Ising spins.

Subcutaneous infection caused by Blastoschizomyces capitatus post allogeneic hematopoietic transplant and its successful treatment with voriconazole.

We describe a 33-year-old man with relapsed acute myelogenous leukemia who developed subcutaneous nodules >6 months after allogeneic hematopoietic stem cell transplant. These nodules were caused by Blastoschizomyces capitatus. The lesions progressed after treatment with a posaconazole suspension. The lesions resolved after switching to voriconazole, which was given for 21 weeks. B. capitatus is a rare infection affecting immunocompromised patients, which responds to azoles.

Cysticercosis of the masseter: MRI and sonographic correlation.

Cysticercal involvement of the masseter is an uncommon manifestation of a relatively common parasitic infestation. Sonographic evaluation of many isolated cases of cysticercosis has been extensively described. However, there are scanty reports on MRI appearance of cysticercal involvement of the masseter. This report presents classical imaging appearance of cysticercal involvement of the masseter on sonography and MRI. The pattern of the disease and MRI appearance of lesions in the masseter, highlighting the role of diffusion-weighted images, are described.

Pneumoparotid in "puffed cheek" computed tomography: incidence and relation to oropharyngeal conditions.

Pneumoparotid is common in patients with lesions of the oral cavity who have diagnostic computed tomography (CT) with the "puffed cheek" technique. Although such observations are often noted, we could find few papers about the incidence in relation to oropharyngeal conditions. We present a retrospective series of 47/300 patients who developed pneumoparotid during multidetector CT examination of the oropharyngeal region to assess the incidence and any possible correlation with regional disease. Patients were followed up for any symptoms and also for complications. In 14 patients the pneumoparotid was right-sided, in 17 left-sided, and in 16 it was bilateral. There was a significant association between the incidence of pneumoparotid and the site of disease, it being stronger (p<0.001) with lesions in the oral cavity than with those in the oropharynx and hypopharynx. Apart from brief discomfort, none of the patients had any symptoms after the procedure. In summary, pneumoparotid developed in 47/300 (16%) of our patients after multidetector CT when the "puffed cheek" technique was used, and was more common in patients with lesions of the oral cavity and anterior tongue than among patients with lesions of the oropharyngeal, nasopharyngeal, and hypopharyngeal regions. Few patients experienced transient fullness immediately after the procedure. None of our patients had lasting or infective symptoms.

Improved hemostasis in hemophilia mice by means of an engineered factor Va mutant.

BACKGROUND: Factor (F)VIIa-based bypassing not always provides sufficient hemostasis in hemophilia. OBJECTIVES: To investigate the potential of engineered activated factor V (FVa) variants as bypassing agents in hemophilia A. METHODS: Activity of FVa variants was studied in vitro using prothrombinase assays with purified components and in FV- and FVIII-deficient plasma using clotting and thrombin generation assays. In vivo bleed reduction after the tail clip was studied in hemophilia A mice. RESULTS AND CONCLUSIONS: FVa mutations included a disulfide bond connecting the A2 and A3 domains and ones that rendered FVa resistant to inactivation by activated protein C (APC). '(super) FVa,' a combination of the A2-A3 disulfide (A2-SS-A3) to stabilize FVa and of APC-cleavage site mutations (Arg506/306/679Gln), had enhanced specific activity and complete APC resistance compared with wild-type FVa, FVL eiden (Arg506Gln), or FVaL eiden (A2-SS-A3). Furthermore, (super) FVa potently increased thrombin generation in vitro in FVIII-deficient plasma. In vivo, (super) FVa reduced bleeding in FVIII-deficient mice more effectively than wild-type FVa. Low-dose (super) FVa, but not wild-type FVa, decreased early blood loss during the first 10 min by more than two-fold compared with saline and provided bleed protection for the majority of mice, similar to treatments with FVIII. During the second 10 min after tail cut, (super) FVa at high dose, but not wild-type FVa, effectively reduced bleeding. These findings suggest that (super) FVa enhances not only clot formation but also clot stabilization. Thus, (super) FVa efficiently improved hemostasis in hemophilia in vitro and in vivo and may have potential therapeutic benefits as a novel bypassing agent in hemophilia.

Controlled magnetic reversal in Permalloy films patterned into artificial quasicrystals.

We have patterned novel Permalloy thin films with quasicrystalline Penrose P2 tilings and measured their dc magnetization and ferromagnetic resonance absorption. Reproducible anomalies in the hysteretic, low-field data signal a series of abrupt transitions between ordered magnetization textures, culminating in a smooth evolution into a saturated state. Micromagnetic simulations compare well to experimental dc hysteresis loops and ferromagnetic resonance spectra and indicate that systematic control of magnetic reversal and domain wall motion can be achieved via tiling design, offering a new paradigm of magnonic quasicrystals.

Syringocystadenoma papilliferum of the scalp in an adult male - a case report.

Syringocystadenoma papilliferum is a benign adnexal skin tumour of the apocrine or the eccrine type with characteristic histological features and varied and non-distinct clinical findings. It is relatively a rare neoplasm, which is called as a childhood tumour, since it usually appears at birth or during puberty. A case of syringocystadenoma papilliferum of the scalp in an adult male has been presented, which was clinically diagnosed at first as keratocanthoma of the scalp but was later histologically confirmed as syringocystadenoma papilliferum.

A DPP-IV-resistant triple-acting agonist of GIP, GLP-1 and glucagon receptors with potent glucose-lowering and insulinotropic actions in high-fat-fed mice.

AIMS/HYPOTHESIS: We designed a chemically modified, enzyme-resistant peptide with triple-acting properties based on human glucagon with amino acid substitutions aligned to strategic positions in the sequence of glucose-dependent insulinotropic polypeptide (GIP). METHODS: Y(1)-dA(2)-I(12)-N(17)-V(18)-I(27)-G(28,29)-glucagon (termed YAG-glucagon) was incubated with dipeptidylpeptidase IV (DPP-IV) to assess stability, BRIN-BD11 cells to evaluate insulin secretion, and receptor-transfected cells to examine cAMP production. Acute glucose-lowering and insulinotropic properties of YAG-glucagon were assessed in National Institutes of Health (NIH) Swiss mice, while longer-term actions on glucose homeostasis, insulin secretion, food intake and body weight were examined in high-fat-fed mice. RESULTS: YAG-glucagon was resistant to DPP-IV, increased in vitro insulin secretion (1.5-3-fold; p < 0.001) and stimulated cAMP production in GIP receptor-, glucagon-like peptide-1 (GLP-1) receptor- and glucagon receptor-transfected cells. Plasma glucose levels were significantly reduced (by 51%; p < 0.01) and insulin concentrations increased (1.2-fold; p < 0.01) after acute injection of YAG-glucagon in NIH Swiss mice. Acute actions were countered by established GIP, GLP-1 and glucagon antagonists. In high-fat-fed mice, twice-daily administration of YAG-glucagon for 14 days reduced plasma glucose (40% reduction; p < 0.01) and increased plasma insulin concentrations (1.8-fold; p < 0.05). Glycaemic responses were markedly improved (19-48% reduction; p < 0.05) and insulin secretion enhanced (1.5-fold; p < 0.05) after a glucose load, which were independent of changes in insulin sensitivity, food intake and body weight. CONCLUSIONS/INTERPRETATION: YAG-glucagon is a DPP-IV-resistant triple agonist of GIP, GLP-1 and glucagon receptors and exhibits beneficial biological properties suggesting that it may hold promise for treatment of type 2 diabetes.

Emergency do not consume/do not use concentrations for blended phosphates in drinking water.

The U.S. Congress [PL 107-188] amended the Safe Drinking Water Act and required each community water system serving more than 3,000 people to conduct vulnerability assessments. These assessments address potential circumstances that could compromise the safety and reliability of municipal water. The present evaluation concerns the concentrations of the blended phosphates (also known as polyphosphates, condensed complex phosphates, polyphosphate glassy balls, and pyrophosphates) intended to aid regulatory agencies in decisions to avoid contact with affected water. Polyphosphates are direct food additives and they are used to treat municipal drinking water, but depending upon the concentration and duration of exposure these substances can induce chemical burns. Ingested polyphosphates are degraded by phosphatase enzymes to monophosphates, substances that are over-the-counter bowel purgatives. High oral doses of the monophosphates can induce transient hyperphosphatemia in older and susceptible young people, which can lead to acute phosphate nephropathy. In some patients, the condition is fatal. Based on the acute diarrhea after the ingestion of a single oral dose of monobasic (NaH2PO(4)) and dibasic (Na2HPO(4)) monophosphates in adults, a do not consume concentration of 600 mg PO(4)/L can be derived. Based on mild local irritation after topical application of 1.0% sodium metaphosphate [(NaPO(3))6 • H2O] to intact skin of sensitive volunteers, a do not use concentration of 8,000 mg PO4/L can be assigned. Given the lack of eye irritation in rabbits after direct instillation of 0.2% (NaPO(3))6 • H2O, an acute ocular contact limit of 50 mg PO4/L serves as the overall do not use level.

Emergency Do Not Consume/do Not Use concentrations for potassium permanganate in drinking water.

Over the past decade, regulatory authorities and water purveyors have become increasingly concerned with accidental or intentional adulteration of municipal drinking water. Emergency response guidelines, such as the 'Do Not Consume' or use concentration limits derived herein, can be used to notify the public in such cases. Potassium permanganate (KMnO(4)) is used to control iron concentrations and to reduce the levels of nuisance materials that affect odor or taste of finished drinking water. Manganese (Mn) is recognized an essential nutrient, permanganate (MnO4 (-)) and manganous (Mn(+2)) ions are caustic, and the acute toxicity of KMnO(4) is defined by its oxidant/irritant properties and by the toxicity of Mn. Ingestion of small amounts (4-20 mg/kg) of aqueous KMnO(4) solutions that are above 200 mg/L causes gastrointestinal distress, while bolus ingestion has caused respiratory arrest following coagulative necrosis and hemorrhage in the esophagus, stomach, or liver. Dilute KMnO(4) solutions (1-100 mg/L) are used as a topical antiseptics and astringents, but >1:5000 (200 mg/L) dilutions can irritate or discolor sensitive mucous membranes and direct skin or ocular contact with concentrated KMnO(4) can perforate tissues. Based on clinical experience with 200 mg/L KMnO(4), a Do Not Consume concentration of 7 mg/L KMnO(4) (equivalent to 2 mg Mn/L) is recommended. Recognizing limited empirical data from which to calculate an ocular reference value, a skin contact 'Do Not Use' concentration of 30 mg Mn/L is recommended based on the skin irritation in some patients after a 10-min contact with 100 mg KMnO4/L.