A Multidimensional Approach for School-Aged Children who Stutter.

Therapy for school-aged children who stutter (CWS) and their parents should be holistic, individualized, and multidimensional, considering the child within their real-life context and using a solution rather than problem-focused approach; highlighting and drawing on the strengths, resources, values; and coping skills that each family brings. Therapy at the Michael Palin Centre draws on a number of psychological approaches, including solution-focused brief therapy, cognitive behavior therapy, acceptance and commitment therapy, and compassion-focused therapy. Aspects of these approaches are discussed in this article to describe the therapeutic intervention for two school-aged CWS (aged 8 and 15 years). The Palin Model (2019) is used to conceptualize the factors that influence stuttering, as well as the different components of therapy that may be relevant for each individual family. The overarching aim of therapy, for children to become competent and effective communicators, whether they stutter or not, is described through a range of practical therapeutic activities, including exploring communication skills, openness and desensitization, exploring thoughts and feelings around stuttering, building confidence, expanding comfort zones, and developing self-efficacy. Qualitative and quantitative outcomes are presented for each clinical case.

Palin parent-child interaction therapy with children with autism spectrum disorder and stuttering.

INTRODUCTION: It is estimated that 8% of children who stutter (CWS) have autism spectrum disorder (ASD) Briley & Ellis (2018). There is evidence that interventions for CWS and interventions for children with ASD can be effective, but there is little evidence to guide clinical decision making when working with CWS with a co-existing diagnosis of ASD. Palin Parent-Child Interaction (PCI) therapy Kelman & Nicholas (2020) is an evidence-based intervention for CWS, with the authors suggesting that the approach may be beneficial for CWS with ASD. The aim of this study was to examine outcomes for three CWS with ASD who received Palin PCI at a specialist centre for stuttering in London. METHOD: The participants were three CWS with ASD aged 4;5, 6;7 and 7;7. Assessments were administered before therapy, and then at three, six and twelve months after therapy began. Outcome measures included stuttering frequency, child's communication attitude, parents' perception of the impact of stuttering on the child, the severity of stuttering and its impact on the parents, and parents' knowledge and confidence in managing stuttering. RESULTS: All three children showed improvement in three or more variables. Four out of five parents reported reduced impact of stuttering on the child and themselves following therapy, and change was maintained one year post-therapy. All five parents reported increased knowledge of stuttering and confidence in managing it after therapy, and four parents maintained these changes for a year. CONCLUSIONS: Over a one year period, these CWS with ASD who received Palin PCI showed change across multiple variables. The observed increases in parent knowledge and confidence were comparable to previously published data. These preliminary findings suggest that CWS with ASD and their parents can benefit from Palin PCI therapy and that further experimental evaluation of this approach with this client group is indicated.

Antibiogram and molecular characterization of multi-drug resistant microorganisms isolated from urinary tract infections.

Bacteria are the commonest etiological factor among the microbes that cause UTIs. The most prevalent bacteria identified in the lab are Escherichia coli, Klebsiella pneumonia and Pseudomonas aeruginosa. Antibiotics are the empiric therapy for such infections but the reoccurrence rate is becoming high owing to the development of resistance due to their irrational and indiscriminate use across the globe. This study was designed on UTI cases of OPD, Medical, Nephrology, Surgical, Main OT, Urology and ICU wards of Allied hospital Faisalabad. 11 antibiotics were used which showed that E. coli is sensitive to Amikacin, Gentamicin, Imipenem, Piperacillin tazobactam, and Polymyxin B. Klebsiella pneumonia showed sensitivity for Amikacin, Gentamicin, Nitrofurantoin, Imipenem, Polymyxin B, Piperacillin tazobactam and Trimethoprim-sulfamethoxazole. While Pseudomonas aurignosa showed resistance to Amikacin, Ciprofloxacin, Gentamicin, Piperacillin tazobactam, Imipenem, and Polymyxin B. E. coli exhibited the highest sensitivity for Piperacillin tazobactam, Klebsiella pneumonia for Imipenem and Pseudomonas aurignosa for Ciprofloxacin. Further, the isolated DNA samples of these microorganisms were confirmed by gel electrophoresis and subjected to molecular characterization by performing trace file and phylogenetic tree analysis.

Water Flow and Dissolved MnII Alter Transformation of Pipemidic Acid by Manganese Oxide.

Manganese oxides have been proposed as promising geomedia to remove trace organic contaminants in both natural soils and artificial infiltration systems. Although MnOx-based redox processes have been largely investigated, little is known on the effects of water flow and dissolved MnII on manganese-mediated redox reactions in saturated porous media. Here, we have demonstrated that the reactive transport of a widely used quinolone antibiotic, pipemidic acid (PIP), in MnO2-coated sand (MCS) columns is altered by the presence of dissolved MnII, generated in situ as reduced ions or present in inflow solution. Decreasing the flow rate or flow interruption facilitated oxidation reactions and generated redox byproducts (MnII and PIPox). However, preloading of MCS columns with dissolved MnII led to suppressed reactivity with PIP. When PIP and MnII are simultaneously injected, competition between PIP and MnII for binding at the edge sites takes place during the initial kinetic phase of reaction, while at a later breakthrough time MnII will occupy both edge and vacancy sites due to the continuous supply of MnII. We also developed a reactive transport model that accounts for adsorption kinetics to predict changes in transport behavior of antibiotics in the presence of different doses of dissolved MnII. This work has strong implications for an accurate assessment of the reactivity of manganese oxides used as engineered geomedia for quinolone remediation and in developing transport models of antibiotics in natural systems.

Bioactivity of Isostructural Hydrogen Bonding Frameworks Built from Pipemidic Acid Metal Complexes.

We report herein three novel complexes whose design was based on the approach that consists of combining commercially available antibiotics with metals to attain different physicochemical properties and promote antimicrobial activity. Thus, new isostructural three-dimensional (3D) hydrogen bonding frameworks of pipemidic acid with manganese (II), zinc (II) and calcium (II) have been synthesised by mechanochemistry and are stable under shelf conditions. Notably, the antimicrobial activity of the compounds is maintained or even increased; in particular, the activity of the complexes is augmented against Escherichia coli, a representative of Gram-negative bacteria that have emerged as a major concern in drug resistance. Moreover, the synthesised compounds display similar general toxicity (Artemia salina model) levels to the original antibiotic, pipemidic acid. The increased antibacterial activity of the synthesised compounds, together with their appropriate toxicity levels, are promising outcomes.

Earlier generation quinolones can be useful in identifying Haemophilus influenzae strains with low susceptibility to quinolone isolated from paediatric patients.

PURPOSE: Haemophilus influenzae strains with low susceptibility to quinolones have recently emerged in the paediatric field in Japan. These strains are judged as 'susceptible' in routine susceptibility tests, although they may survive after quinolone treatment. Therefore, we aimed to construct a simple and cost-effective identification method for low-susceptibility strains using disc diffusion assays. METHODOLOGY: A total of 33 H. influenzae clinical isolates and a control strain were used. For the disc diffusion assay, levofloxacin, norfloxacin, nalidixic acid and pipemidic acid were employed. Correlations between the inhibition zone diameter and amino acid substitutions were evaluated. RESULTS: All of the tested strains formed clear inhibition zones on both levofloxacin and norfloxacin discs. By contrast, none of the low-susceptibility strains showed inhibition zones against nalidixic acid, while the low-susceptibility strains with amino acid substitutions in both GyrA and ParC did not show inhibition zones against pipemidic acid discs, indicating that low-susceptibility strains can be detected with high sensitivity and specificity by the presence or absence of inhibition zones for earlier quinolones. CONCLUSION: A disc diffusion test combining results from nalidixic acid and pipemidic acid can detect low-susceptibility strains harbouring amino acid substitutions without the need for genetic analysis. This test can help reduce inappropriate and unnecessary fluoroquinolone use.

A New Approach for Improving the Antibacterial and Tumor Cytotoxic Activities of Pipemidic Acid by Including It in Trimethyl-ß-cyclodextrin.

Pipemidic acid (HPPA) is a quinolone antibacterial agent used mostly to treat gram-negative infections of the urinary tract, but its therapeutic use is limited because of its low solubility. Thus, to improve drug solubility, natural cyclodextrins (CDs) are used for their ability of including guest molecules within their cavities. The aim of this work was to evaluate the antibacterial activity and the preliminary anticancer activity of HPPA included into Heptakis (2,3,6-tri-O-methyl)-ß-cyclodextrin (TRIMEB) as a possible approach for a new innovative formulation. The inclusion complex of HPPA with TRIMEB was prepared in solid state by the kneading method and confirmed by FT-IR and powered X-ray diffraction. The association in aqueous solutions of pipemidic acid with TRIMEB was investigated by UV-Vis spectroscopy. Job's plots have been drawn by UV-visible spectroscopy to confirm the 1:1 stoichiometry of the host⁻guest assembly. The antibacterial activity of HPPA, TRIMEB and of their complex was tested on Escherichia coli, Pseudomonas aeruginosa, and Staphilococcus aureus. The complex was able to increase 47.36% of the median antibacterial activity of the free HPPA against E. coli (IC50 = 249 µM vs. 473 µM). Furthermore, these samples were tested on HepG-2 and MCF-7. After 72 h, the median tumoral cytotoxicity exerted by the complex was increased by 78.08% and 94.27% for HepG-2 and MCF-7 respectively, showing a stronger bioactivity of the complex than the single HAPPA.

How to unravel the chemical structure and component localization of individual drug-loaded polymeric nanoparticles by using tapping AFM-IR.

AFM-IR is a photothermal technique that combines AFM and infrared (IR) spectroscopy to unambiguously identify the chemical composition of a sample with tens of nanometer spatial resolution. So far, it has been successfully used in contact mode in a variety of applications. However, the contact mode is unsuitable for soft or loosely adhesive samples such as polymeric nanoparticles (NPs) of less than 200 nm of wide interest for biomedical applications. We describe here the theoretical basis of the innovative tapping AFMIR mode that can address novel challenges in imaging and chemical mapping. The new method enables gaining information not only on NP morphology and composition, but also reveals drug location and core-shell structures. Whereas up to now the locations of NP components could only be hypothesized, tapping AFM-IR allows accurately visualizing both the location of the NPs' shells and that of the incorporated drug, pipemidic acid. The preferential accumulation of the drug in the NPs' top layers was proved, despite its low concentration (<1 wt%). These studies pave the way towards the use of tapping AFM-IR as a powerful tool to control the quality of NP formulations based on individual NP detection and component quantification.

Synthesis and in vitro antimicrobial activity screening of new pipemidic acid derivatives.

This article describes the synthesis and antimicrobial activity evaluation of new pipemidic acid derivatives. New compounds were obtained on the basis of Mannich reaction of 4,5-disubstituted 1,2,4-triazole-3-thiones with pipemidic acid. Antimicrobial tests revealed high antibacterial activity of obtained derivatives. Gram-negative rods belonging to Enterobacteriaceae family were particularly most sensitive to new pipemidic acid derivatives. Synthesized compounds exhibited very strong activity towards Proteus mirabilis ATCC 12453, Salmonella typhimurium ATCC 14028 and Escherichia coli ATCC 25922. The minimum inhibitory concentrations of new pipemidic acid derivatives which inhibited the growth of these bacteria were 0.98-7.81 µg/ml, 0.98-7.81 µg/ml and 0.98-3.91 µg/ml, respectively. The antibacterial activity of newly synthesized pipemidic acid derivatives in many cases was far better than the activity of substances used as positive controls (nitrofurantoin, cefuroxime, ampicillin and pipemidic acid).

Synthesis of novel tetrazole containing hybrid ciprofloxacin and pipemidic acid analogues and preliminary biological evaluation of their antibacterial and antiproliferative activity.

A series of 1-substituted-1H-tetrazole-5-thiol building blocks were synthesized and introduced to the N-4 piperazinyl group at C-7 position of the quinolone core, and these novel compounds (5a-g and 8a-g) were screened for their antibacterial and antiproliferative activities. Bioactive assay studies manifested that most of new compounds exhibited significant antibacterial activity against the tested strains, including multi-drug-resistant MRSA in comparison with reference drugs ciprofloxacin, streptomycin B and pipemidic acid. Among the synthesized compounds, only ciprofloxacin (5a-g) derivatives displayed significant activity ([Formula: see text]) compared to reference drugs. In addition, these compounds were evaluated for their in vitro inhibition of human cancer cell lines viz human cervical carcinoma cell line (SiHA), breast adenocarcinoma (MDA-MB-235) and human pancreas carcinoma (PANC-1) cell lines by using the SRB assay method. Most of the target compounds showed broad potent growth inhibition activity ([Formula: see text]) against all the tested cancer cell lines compared with reference drug. The most promising active compounds in this series were 5c, 5d, 8c, 8d and 8f endowed with excellent antiproliferative activity. A new class of compounds was designed rationally by introducing tetrazole building block on N-4 piperazinyl group at C-7 position of quinolones core. The titled compounds were evaluated for their preliminary antibacterial and antiproliferative activities.

Effects of Pipemidic Acid, Phenazopyridine HCL and Sodium Diclofenac on Pain Perception Following Endoscopic Urological Surgery: Double-blinded Randomized-Controlled Trial.

AIM: to evaluate the analgesic effect, the side effects and the safety of analgesics following endoscopic urological procedure. METHODS: eighty patients who underwent endoscopic urological surgery at Kardinah Hospital, Tegal from June to July 2015 were divided into four groups. The experimental group was administered analgesic for 4 days pipemidic acid (A) 400 mg bid, or phenazopyridine (B) 200 mg tid, or sodium diclofenac (C) 50 mg bid and the control (D) group was administered placebo tid for 4 days. The analgesic effects were assessed using Visual Analog Scale (VAS). Association between variables was assessed using Cramers V and Kruskall Wallis. RESULTS: the endoscopic urological procedures consisted of 30 patients for URS, 6 patients for lithotripsy, 17 patients for TURP, 24 patients for removal JJ stent and 3 patients for cystoscopy. The mean age of group A, B, C and D (control) was 50.1 (13.7), 50.7 (14.8), 49.1 (13.4), and 49.6 (14.3) years, respectively, and follow-up period was 7 days. The VAS score in all experimental groups was less than control group on day 1 to 7 following endoscopic urological procedures (p<0.05). In the experimental group, there was no difference between groups B and C (p>0.05). Group A demonstrated a more favourable analgesic effect than B and C (p<0.05). No serious side effects were detected in any of the cases. CONCLUSION: we conclude that oral analgesics are effective for pain relief following endoscopic urological surgery. Pipemidic acid was found to have a superior analgesic effect than phenazopyridine HCl and sodium diclofenac.

Synthesis, characterization, and evaluation of the antimicrobial potential of copper(II) coordination complexes with quinolone and p-xylenyl-linked quinolone ligands.

The antimicrobial properties of copper have been known to mankind since the ancient times. In a coordination chemistry approach to develop novel antimicrobial agents, the quinolone antimicrobial agents ciprofloxacin (Hcipro) and pipemidic acid (Hpia), as well as dimers thereof (piperazinyl-linked with a p-xylenyl moiety) were complexed with copper(II). The synthesis and antimicrobial evaluation of bis(ciprofloxacino)copper(II) [Cu(cipro)2], bis(pipemido)copper(II) [Cu(pia)2], and the corresponding dimer complexes, [Cu2(ciproXcipro)2] and [Cu2(piaXpia)2], are reported. No combinational or synergistic effect between copper(II) and the respective quinolone ligands was observed in vitro.

[REHABILITATION OF PATIENTS WITH URIC ACID AND MIXED UROLITHIASIS].

This paper presents evaluation of rehabilitation effectiveness of 113 patients aged 19-78 years diagnosed as having mixed and uric acid stones. 88 patients with uric acid stones 0,5-2,5 cm were assigned to group 1 and treated with Trometamol N parenteral litholis and a complex metaprophilaxis by dietary supplements Prolit and Urisan. 25 patients with mixed stones 1-3,5 cm were allocated to group 2 and treated with external shock wave lithotripsy and complex metaprophilaxis by dietary supplements Prolit Super Septo and Urisan. Positive results were achieved in all the patients. In the patients of group 1 the stones were completely dissolved. In group 2 treatment resulted in stone disintegration and clearance of small fragments 0,4 cm after partial dissolution.

Clinical evaluation of herbal coded formulation Cran-off to Urixin in the treatment of urinary tract infection.

Urinary Tract Infections are the largest group of infections after the respiratory tract infections. In 85% of the cases the causative organism is E. Coli. A clinical trial was conducted to evaluate the efficacy of coded herbal formulation "Cranoff" (Test drug) for the treatment of Urinary tract infection comparing with Urixin (Control). One hundred and thirty patients suffering from Urinary tract infection from both groups (Males: 45, mean age: 34±14 and females: 85, mean age: 33±13 year, range: 15-55) were enrolled in the trial and divided in to two groups according to treatment regimens. Cranoff (Test drug) 500mg two capsules and Urixin (Pipemidic Acid Trihydrate JP15) (Control) 400mg capsules twice daily were prescribed for 2-3 weeks. Urinary tract infection was improved in 23 (35.38%) patients out of 65 patients by the use of Cranoff (Test drug), and in 15 (23.07%) patients out of 65 by the use of Urixin (Control drug). Furthermore, there was a significant improvement in Urinary tract infection associated clinical features as compared to Urixin. It is concluded that Cranoff possesses a therapeutic value for the improvement of urinary tract infection and its associated symptoms as compared to Urixin.

ß-Cyclodextrin inclusion complex to improve physicochemical properties of pipemidic acid: characterization and bioactivity evaluation.

The aptitude of cyclodextrins (CDs) to form host-guest complexes has prompted an increase in the development of new drug formulations. In this study, the inclusion complexes of pipemidic acid (HPPA), a therapeutic agent for urinary tract infections, with native ß-CD were prepared in solid state by kneading method and confirmed by FT-IR and 1H NMR. The inclusion complex formation was also characterized in aqueous solution at different pH via UV-Vis titration and phase solubility studies obtaining the stability constant. The 1:1 stoichiometry was established by a Job plot and the inclusion mechanism was clarified using docking experiments. Finally, the antibacterial activity of HPPA and its inclusion complex was tested on P. aeruginosa, E. coli and S. aureus to determine the respective EC50s and EC90s. The results showed that the antibacterial activity of HPPA:ß-CD against E. coli and S. aureus is higher than that of HPPA. Furthermore, HPPA and HPPA:ß-CD, tested on human hepatoblastoma HepG2 and MCF-7 cell lines by MTT assay, exhibited, for the first time, antitumor activities, and the complex revealed a higher activity than that of HPPA. The use of ß-CD allows an increase in the aqueous solubility of the drug, its bioavailability and then its bioactivity.

Prebiotic properties of galursan HF 7K on mouse gut microbiota.

BACKGROUND: With the rise of antibiotic resistance, new alternatives are being sought to effectively modulate the characteristics of gut microbiota to obtain pathogen resistance without the use of antibiotics. In the past, an oligosaccharide derivative of carrots, galursan HF 7K (GHF7K), has been used clinically in Austria and recently in the fowl-industry to promote health. This study examined the potential role of GHF7K as a prebiotic to alter the gut microbiota in mice. METHODS: Mice were fed either a control diet (CT) or a diet containing 2% GHF7K in the water and chow for 2 weeks, and weight, food and water consumption, gut microbiota and ion composition of the intestinal fluid were examined. RESULTS: Dietary supplement of GHF7K did not alter mouse weight or daily food consumption. Additionally, no changes were observed in the total number of luminal or mucosa-associated bacteria populations in GHF7K-fed mice. GHF7K supplementation significantly altered the composition of luminal, and to a less extent, mucosa-associated bacterial populations at the level of the phyla, with region-specific differences. Similar to antibiotic use, Proteobacteria number was increased in the ileum and colon of GHF7K-fed mice, with no changes in the number of beneficial Lactobacillus and Bifidobacterium genera of phylum Firmicutes. Corresponding with the altered gut microbiota, changes in the ion composition of the intestinal fluid were observed. An increased Cl(-) concentration was observed in the duodenum and jejunum, while the Na(+) concentration was increased in the cecum of GHF7K-fed mice. Decreases were observed in the K(+) concentration in the cecum and distal colon. CONCLUSIONS: Dietary supplement of GHF7K is capable of altering the gut microbiota, which correlates to changes in the intestinal environment. These data suggest that GHF7K dietary supplement can purposefully be used to alter the gut microbiota, and thus could potentially represent an alternative approach to prophylactic antibiotic use.

Quinolone prophylaxis in transrectal ultrasound guided prostate biopsy: an eight-year single center experience.

We retrospectively evaluated the efficacy of prophylaxis with pipemidic acid and levofloxacin in transrectal ultrasound guided prostate biopsy (TRUSP-Bx). From January 2002 to December 2004, patients receiving oral pipemidic acid 500 mg twice daily for three days with or without a preoperative intravenous cefazolin 1 gm injection comprised group A. Between January 2005 and December 2009, patients receiving oral levofloxacin 500 mg one hour before biopsy comprised group B. We calculated the annual febrile urinary tract infection (fUTI) rates. Patients' characteristics, including age, prophylactic antibiotics, biopsy core numbers, pathologic results, PSA, and the spectrums and susceptibility of pathogens, were also evaluated. A total of 1313 (35.5%) patients belonged to group A, while 2381 (64.5%) patients belonged to group B. Seventy-three patients experienced postoperative infectious complications. There was a significant difference in the fUTI rate between groups A and B (3.7% versus 1.0%, P < 0.001). The yearly fUTI rates varied from 0.6 to 3.9% between 2002 and 2009. Of the 73 patients with fUTI, those receiving levofloxacin prophylaxis were more likely to harbor fluoroquinolone-resistant pathogens (P < 0.001). E. coli was the most common pathogen in both groups. Levofloxacin remains effective and appears superior to pipemidic acid based prophylaxis.

[Treatment and metaphylaxis of urate and mixed urolithiasis].

We estimated the efficacy of combined treatment and metaphylaxis of urate and mixed urolithiasis in 87 patients aged 18-87 years. The patients were divided into two groups: 68 patients of group 1 (the size of the concrements between 5-25 mm) have undergone parenteral litholysis of the drug trometamol N and metaphylaxis with biologically active additives prolit and urisan; 19 patients of group 2 have undergone extracorporeal shock-wave lithotripsy with parenteral litholysis and metaphylaxis by using biologically active additives prolit septo and urisan. Positive results were achieved in all the patients. In group 1 the concrements dissolved completely. In group 2 small fragments up to 4 mm eliminated after partial solution.

[Treatment and metaphylaxis of gout complicated by nephropathy and urolithiasis].

The evaluation of clinical efficacy of combined treatment and metaphylaxis in 58 patients with gout complicated by nephropathy and urolithiasis was performed. The study included 41 (71%) men and 27 (29%) women aged 44 to 88 years (mean age - 58 +/- 7 years). All patients received parenteral therapy with trometamol H, 5 -10 infusion for the course, an average of 7 infusions. For the metaphylaxis, all patients received biologically active supplement urisan 2 tablets 2 times a day during next three months against the background of drug therapy. Findings indicate a high clinical efficacy of the trometamol H in the combined treatment of patients with gout, complicated by nephropathy and urolithiasis, considering that improvement of renal function, microcirculation in the renal parenchyma, increased glomerular filtration rate, normalization of nitrogenous wastes levels, partial or complete dissolution of concretions of the kidneys, a significant decrease in the tophs size, an increase in motor activity were observed, which ultimately improves the quality of life for these patients. Metaphylaxis using urisan for 3 months on a background of traditional therapy contributed to a stable normalization of blood uric acid levels, which prevented the exacerbation of underlying disease and recurrent stone formation. These data allow to recommend reducing the dose of traditional anti-gout drugs and conducting repeated course of metaphylaxis with the urisan after 5-6 months during 3 months.