The utility of ChatGPT as a generative medical translator.

PURPOSE: Large language models continue to dramatically change the medical landscape. We aimed to explore the utility of ChatGPT in providing accurate, actionable, and understandable generative medical translations in English, Spanish, and Mandarin pertaining to Otolaryngology. METHODS: Responses of GPT-4 to commonly asked patient questions listed on official otolaryngology clinical practice guidelines (CPG) were evaluated with the Patient Education materials Assessment Tool-printable (PEMAT-P.) Additional critical elements were identified a priori to evaluate ChatGPT's accuracy and thoroughness in its responses. Multiple fluent speakers of English, Mandarin, and Spanish evaluated each response generated by ChatGPT. RESULTS: Total PEMAT-P scores differed between English, Mandarin, and Spanish GPT-4 generated responses depicting a moderate effect size of language, Eta-Square 0.07 with scores ranging from 73 to 77 (P-value = 0.03). Overall understandability scores did not differ between English, Mandarin, and Spanish depicting a small effect size of language, Eta-Square 0.02 scores ranging from 76 to 79 (P-value = 0.17), nor did overall actionability scores Eta-Square 0 score ranging 66-73 (P-value = 0.44). Overall a priori procedure-specific responses similarly did not differ between English, Spanish, and Mandarin Eta-Square 0.02 scores ranging 61-78 (P-value = 0.22). CONCLUSION: GPT-4 produces accurate, understandable, and actionable outputs in English, Spanish, and Mandarin. Responses generated by GPT-4 in Spanish and Mandarin are comparable to English counterparts indicating a novel use for these models within Otolaryngology, and implications for bridging healthcare access and literacy gaps. LEVEL OF EVIDENCE: IV.

Synthesis, In Silico Study, and In Vitro Antifungal Activity of New 5-(1,3-Diphenyl-1H-Pyrazol-4-yl)-4-Tosyl-4,5-Dihydrooxazoles.

The increase in multi-drug resistant Candida strains has caused a sharp rise in life-threatening fungal infections in immunosuppressed patients, including those with SARS-CoV-2. Novel antifungal drugs are needed to combat multi-drug-resistant yeasts. This study aimed to synthesize a new series of 2-oxazolines and evaluate the ligands in vitro for the inhibition of six Candida species and in silico for affinity to the CYP51 enzymes (obtained with molecular modeling and protein homology) of the same species. The 5-(1,3-diphenyl-1H-pyrazol-4-yl)-4-tosyl-4,5-dihydrooxazoles 6a-j were synthesized using the Van Leusen reaction between 1,3-diphenyl-4-formylpyrazoles 4a-j and TosMIC 5 in the presence of K2CO3 or KOH without heating, resulting in short reaction times, high compound purity, and high yields. The docking studies revealed good affinity for the active site of the CYP51 enzymes of the Candida species in the following order: 6a-j > 4a-j > fluconazole (the reference drug). The in vitro testing of the compounds against the Candida species showed lower MIC values for 6a-j than 4a-j, and for 4a-j than fluconazole, thus correlating well with the in silico findings. According to growth rescue assays, 6a-j and 4a-j (like fluconazole) inhibit ergosterol synthesis. The in silico toxicity assessment evidenced the safety of compounds 6a-j, which merit further research as possible antifungal drugs.

Assessing the effectiveness of antimicrobial pouch use for infection prevention in sacral neuromodulation.

INTRODUCTION AND HYPOTHESIS: Sacral neuromodulation (SNM) is a commonly performed procedure for various conditions. Infection rates range as high as 10% and often require operative explantation with resultant increased cost and morbidity. Pouches impregnated with antibiotic have been utilized in cardiovascular procedures with decreasing infectious complications. TYRX is an antibiotic pouch utilizing minocycline and rifampin manufactured by Medtronic. The objective of this study is to investigate the utility of antimicrobial pouches for patients undergoing SNM. METHODS: We retrospectively analyzed our patients undergoing SNM using an antimicrobial pouch and compared them with a historic cohort. Additional variables of interest included post-operative infection, diagnosis of diabetes, weight, and revision case or virgin implant. RESULTS: A total of 170 cases were identified, ranging from March 2017 to November 2022. Overall infection rate was 2.9% with 0 in the antimicrobial pouch cohort (0%) versus 5 in the historic cohort (5.5%; p = 0.04). Groups were similar in terms of body habitus. The group receiving an antimicrobial pouch was noted to be older with a higher percentage of female patients. 85 patients received an antimicrobial pouch and 85 did not. Of the infections, 4 occurred in revision cases (6.9%) and 1 in a virgin implant (0.9%; p = 0.03). No difference was noted in infection rate with regard to a diagnosis of diabetes or body habitus. CONCLUSION: The use of antimicrobial pouches in SNM is associated with a decreased rate of infectious complications. Revision cases displayed a higher rate of infectious complications.

The effect of sugammadex on postoperative urinary retention post-laparoscopic and robotic hysterectomy with and without concomitant procedures.

INTRODUCTION AND HYPOTHESIS: This study was aimed at determining the effect of sugammadex versus a combination of glycopyrrolate and neostigmine (GN) for neuromuscular reversal blockage on transient postoperative urinary retention (TPOUR) in patients undergoing a laparoscopic and robot-assisted laparoscopic hysterectomy. METHODS: We conducted a retrospective cohort study in patients undergoing a laparoscopic or robotic hysterectomy between February 2017 and December 2021. Patients with and without concomitant procedures were included. Demographics and perioperative data were extracted from the patient's medical record. Before discharge, all patients were required to spontaneously void and have a post-void residual of less than 150 ml. RESULTS: We identified 500 patients and 485 were included in the final analysis. We had 319 subjects who received sugammadex and 166 GN combination. Both groups had overall similar demographics and perioperative characteristics. Most patients had a conventional laparoscopy procedure (391 [82.5%]) compared with robotic (83 [17.5%]). Patients who received GN were significantly more likely to be discharged home with an indwelling catheter (odds ratio [OR], 1.82; 95% confidence interval [CI], 1.09-3.05). After adjusting for perioperative medications and sling implantation during the surgery a logistic regression model continued to demonstrate that patients who received GN had significantly higher odds of being discharged with a catheter (OR, 1.79; 95% CI, 1.03-3.12). CONCLUSIONS: Our findings suggest that sugammadex decreases the odds of TPOUR after laparoscopic hysterectomies with and without slings compared with the combination of GN. Additional prospective trials are required to confirm this finding.

Pyrrole-Based Enaminones as Building Blocks for the Synthesis of Indolizines and Pyrrolo[1,2-a]pyrazines Showing Potent Antifungal Activity.

As a new approach, pyrrolo[1,2-a]pyrazines were synthesized through the cyclization of 2-formylpyrrole-based enaminones in the presence of ammonium acetate. The enaminones were prepared with a straightforward method, reacting the corresponding alkyl 2-(2-formyl-1H-pyrrol-1-yl)acetates, 2-(2-formyl-1H-pyrrol-1-yl)acetonitrile, and 2-(2-formyl-1H-pyrrol-1-yl)acetophenones with DMFDMA. Analogous enaminones elaborated from alkyl (E)-3-(1H-pyrrol-2-yl)acrylates were treated with a Lewis acid to afford indolizines. The antifungal activity of the series of substituted pyrroles, pyrrole-based enaminones, pyrrolo[1,2-a]pyrazines, and indolizines was evaluated on six Candida spp., including two multidrug-resistant ones. Compared to the reference drugs, most test compounds produced a more robust antifungal effect. Docking analysis suggests that the inhibition of yeast growth was probably mediated by the interaction of the compounds with the catalytic site of HMGR of the Candida species.

Synthesis and Molecular Docking Studies of Alkoxy- and Imidazole-Substituted Xanthones as α-Amylase and α-Glucosidase Inhibitors.

Current antidiabetic drugs have severe side effects, which may be minimized by new selective molecules that strongly inhibit α-glucosidase and weakly inhibit α-amylase. We have synthesized novel alkoxy-substituted xanthones and imidazole-substituted xanthones and have evaluated them for their in silico and in vitro α-glucosidase and α-amylase inhibition activity. Compounds 6c, 6e, and 9b promoted higher α-glucosidase inhibition (IC50 = 16.0, 12.8, and 4.0 µM, respectively) and lower α-amylase inhibition (IC50 = 76.7, 68.1, and >200 µM, respectively) compared to acarbose (IC50 = 306.7 µM for α-glucosidase and 20.0 µM for α-amylase). Contrarily, derivatives 10c and 10f showed higher α-amylase inhibition (IC50 = 5.4 and 8.7 µM, respectively) and lower α-glucosidase inhibition (IC50 = 232.7 and 145.2 µM, respectively). According to the structure-activity relationship, attaching 4-bromobutoxy or 4'-chlorophenylacetophenone moieties to the 2-hydroxy group of xanthone provides higher α-glucosidase inhibition and lower α-amylase inhibition. In silico studies suggest that these scaffolds are key in the activity and interaction of xanthone derivatives. Enzymatic kinetics studies showed that 6c, 9b, and 10c are mainly mixed inhibitors on α-glucosidase and α-amylase. In addition, drug prediction and ADMET studies support that compounds 6c, 9b, and 10c are candidates with antidiabetic potential.

Nanotechnology as an efficient and effective alternative for wastewater treatment: an overview.

The increase in the surface and groundwater contamination due to global population growth, industrialization, proliferation of pathogens, emerging pollutants, heavy metals, and scarcity of drinking water represents a critical problem. Because of this problem, particular emphasis will be placed on wastewater recycling. Conventional wastewater treatment methods may be limited due to high investment costs or, in some cases, poor treatment efficiency. To address these issues, it is necessary to continuously evaluate novel technologies that complement and improve these traditional wastewater treatment processes. In this regard, technologies based on nanomaterials are also being studied. These technologies improve wastewater management and constitute one of the main focuses of nanotechnology. The following review describes wastewater's primary biological, organic, and inorganic contaminants. Subsequently, it focuses on the potential of different nanomaterials (metal oxides, carbon-based nanomaterials, cellulose-based nanomaterials), membrane, and nanobioremediation processes for wastewater treatment. The above is evident from the review of various publications. However, nanomaterials' cost, toxicity, and biodegradability need to be addressed before their commercial distribution and scale-up. The development of nanomaterials and nanoproducts must be sustainable and safe throughout the nanoproduct life cycle to meet the requirements of the circular economy.

Development and validation across trimester of the Prenatal Eating Behaviors Screening tool.

Rapid screening tools are useful for identifying at-risk patients and referring them for further assessment and treatment, but none exist that consider the unique medical needs of pregnant women with eating disorders (EDs). There is a need for a rapid, sensitive, and specific screening tool that can be used to identify a potential ED in pregnancy. We started with a set of 25 questions, developed from our qualitative work along with other ED screening tools, and tested on a development (n = 190) and validation sample (n = 167). Statistical analysis included factor analysis and logistic regressions with ROC curves. Development and validation samples were combined for trimester analysis (n = 357). Refining the tool to 12 items demonstrated strong internal reliability (development alpha = 0.95, validation alpha = 0.91). With correlated errors, questions demonstrated acceptable CFA fit (development: GFI: 0.91, RMSEA: 0.10, NNFI: 0.95; validation: GFI: 0.85, RMSEA: 0.14, NNFI: 0.86). Similar fits were seen by trimester: first trimester n = 127, GFI: 0.89, RMSEA: 0.12, NNFI: 0.94; second trimester n = 150, GFI: 0.83, RMSEA: 0.14, NNFI: 0.88; third trimester n = 80, GFI: 0.99, NNFI: 0.99. Validation against current ED diagnosis demonstrated acceptable sensitivity and specificity using a cutoff of 39 (development sensitivity = 80.7%, specificity = 79.7%, OR = 16.42, 95% CI: 7.51, 35.88; validation sensitivity = 69.2%, specificity = 86.5%, OR: 17.43, 95% CI: 6.46, 47.01). Findings suggest the PEBS tool can reliably and sensitively detect EDs across pregnancy trimesters with 12 questions. A further implication of this work is to reduce health and mental health treatment disparities through this standard and rapid screening measure to ensure early identification and treatment.

Molecular Recognition of Citroflavonoids Naringin and Naringenin at the Active Site of the HMG-CoA Reductase and DNA Topoisomerase Type II Enzymes of Candida spp. and Ustilago maydis.

Two agents from natural sources, citroflavonoids naringin and naringenin, can target enzymes in pathogenic yeasts responsible for hospital infections and crop failure. The aim of this study was to examine the molecular recognition site for naringin and naringenin on the HMGR and TOPOII enzymes of eleven Candida species and one phytopathogen, U. maydis, and evaluate yeast susceptibility to these flavonoids. The HMGR and TOPOII enzymes were analyzed in silico. The alignment of the two enzymes in the twelve pathogenic organisms with the corresponding enzyme of Homo sapiens revealed highly conserved amino acid sequences. Modeling studies of the enzymes indicated highly conserved structures. According to molecular docking simulations, both citroflavonoids recognized the amino acid residues of the active site of the enzymes. Binding energy values were higher for naringin (-10.75 and -9.38 kcal/mol, respectively) than simvastatin on HMGR (-9.9) and curcumin on TOPOII (-8.37). The appraisal of twenty-nine virtual mutations provided evidence of probable mechanisms of resistance (high binding energy) or susceptibility (low energy) to the drugs and emphasized the role of key residues. An in vitro susceptibility evaluation of the twelve yeasts demonstrated that the two flavonoids have similar or better MIC values than those reported for the reference compounds, obtaining the lowest with Candida dubliniensis (2.5 µg/ml) and U. maydis (5 µg/ml). Based on the present findings, naringin and naringenin could possibly be effective for treating diseases caused by pathogenic yeasts of the Candida species and U. maydis, presumably by inhibition of their HMGR and TOPOII enzymes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12088-021-00980-0.

Inhibitors of DNA topoisomerases I and II applied to Candida dubliniensis reduce growth, viability, the generation of petite mutants and toxicity, while acting synergistically with fluconazole.

The increasing resistance of Candida species to azoles emphasizes the urgent need for new antifungal agents with novel mechanisms of action. The aim of this study was to examine the effect of three DNA topoisomerase inhibitors of plant origin (camptothecin, etoposide and curcumin) on the growth of Candida dubliniensis. The phylogenetic analysis showed a close relationship between the topoisomerase enzymes of C. dubliniensis and Candida albicans. The alignment of the amino acid sequences of topoisomerase I and II of yeasts and humans evidenced conserved domains. The docking study revealed affinity of the test compounds for the active site of topoisomerase I and II in C. dubliniensis. Curcumin and camptothecin demonstrated a stronger in vitro antifungal effect than the reference drugs (fluconazole and itraconazole). Significant synergistic activity between the topoisomerase inhibitors and fluconazole at the highest concentration (750 µM) was observed. Fluconazole induced the petite phenotype to a greater degree than the topoisomerase inhibitors, indicating a tendency to generate resistance. Lower toxicity was found for such inhibitors versus reference drugs on Galleria mellonella larva. The topoisomerase inhibitors exhibited promising antifungal activity, and the DNA topoisomerase enzymes of C. dubliniensis proved to be an excellent model for evaluating new antifungal compounds.

Cyclooctadiene Rh(I) Bis- and Tris(pyrazolyl)aluminate Complexes and Their Catalytic Activity on the Polymerization of Phenylacetylene.

In this work, we report the transfer of alkyl bis- and tris(pyrazolyl)aluminates metalloligands to an electron-rich organotransition metal center. The 16-electron heterobimetallic complexes of rhodium [Rh(COD){Al(Ph2pz)2Me2}] (3) and [Rh(COD){Al(Ph2pz)3Me}] (4) were obtained by metathesis reaction of the sodium bis- (1) and tris(pyrazolyl)aluminate (2) with [RhCl(COD)]2. For 3, 1H and 13C NMR in solution along with DFT calculations are consistent with a κ2-coordination mode of the bis(pyrazolyl)aluminate to a square-planar Rh(I) center. The X-ray structure of 4 shows a similar κ2-coordination mode of the tris(pyrazolyl)aluminate to Rh(I) with a pendant pyrazolyl moiety. The attempted synthesis of aluminate-rhodium complexes with R = CF3, tBu on the pyrazolate ring afforded [Rh(R2pz)(COD)]2 and [R2pzAlMe2]2. Complexes 3 and 4 were investigated as homogeneous catalysts in the polymerization of phenylacetylene (PA). Both complexes showed enhanced catalytic activity compared to analogous rhodium poly(pyrazolyl)borates. Optimized gas-phase DFT geometries of 3, 4, [Rh(COD){B(Ph2pz)2Me2}], and [Rh(COD){B(Ph2pz)3Me}] were used to compare bite angles, while DFT geometries of 3-CO, 4-CO, [Rh(CO)2{B(Ph2pz)2Me2}], and [Rh(CO)2{B(Ph2pz)3Me}] were employed to probe the electronic situation of the rhodium center through IR CO stretching modes. The wider bite angles and the less electron-rich rhodium center of the poly(pyrazolyl)aluminates compared with their borate analogues could be implicated in the better performance of the active catalytic species during polymerization of PA.

Etoposide and Camptothecin Reduce Growth, Viability, the Generation of Petite Mutants, and Recognize the Active Site of DNA Topoisomerase I and II Enzymes in Candida glabrata.

Candidemia, one of the most common invasive fungal infections in hospitalized patients, can lead to death and huge financial losses. Candida albicans is the main causative agent of this disorder and Candida glabrata occupies the second or third place, for which new therapeutic alternatives must be found. The objective of the present study was to evaluate the inhibitory effect of etoposide and camptothecin (inhibitors of deoxyribonucleic acid (DNA) topoisomerase) on the C. glabrata CBS138 strain. Etoposide and camptothecin showed better or similar MIC (minimum inhibitory concentration) (5 and 2.5 µg/mL, respectively), with respect to fluconazole (8 µg/mL) and itraconazole (4 µg/mL). They also suppressed colony formation during the 12-h test. On the other hand, petite colonies were less formed by exposing C. glabrata to etoposide or camptothecin (indicating low toxicity), with respect fluconazole and itraconazole. Such colonies are phenotypically observed as limited growth in medium containing a non-fermentable carbon source, and are genotypically characterized by a partial or total loss of mitochondrial DNA (mtDNA) fragments. Using PCR techniques and cell staining with 4',6-diamidino-2-phenylindole (DAPI), loss of mtDNA was detected only in yeast cells treated with fluconazole. Additionally, molecular docking studies with etoposide and camptothecin showed recognition in the active site of the Topo I and II enzymes from C. glabrata. Since etoposide and camptothecin showed good inhibitory activity and low toxicity on C. glabrata; they should certainly be of interest for the treatment of C. glabrata infections and the design and development of new antifungal compounds derived from these drugs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12088-021-00942-6.

Factors in delay of diagnosis of gynecologic ureteral injuries at a rural academic hospital.

INTRODUCTION AND HYPOTHESIS: Ureteral injuries are a source of morbidity, and delays in diagnosis can increase the risk for long-term sequelae. Our aim was to quantify and describe iatrogenic ureteral injuries in a rural tertiary care center. Our secondary goal was to evaluate the impact of delayed diagnosis of ureteral injury on patient outcomes and whether cystoscopy had any influence on these outcomes. METHODS: A retrospective chart review was undertaken for ureteral injuries, identified by the ICD-9 code from 1997 to 2017 at West Virginia University (WVU) Hospital. Injuries were categorized by procedure, surgeon specialty, location (WVU versus community hospital), and intraoperative cystoscopy. A delay in diagnosis was defined as a ureteral injury sustained during surgery not diagnosed intraoperatively. RESULTS: Forty-six patients were identified with iatrogenic ureteral injury at WVU. Twenty-seven occurred during gynecologic procedures (59%). Fourteen ureteral injuries were sustained at community hospitals and transferred to WVU for evaluation and treatment. Fifty percent of those had a known delay in diagnosis. The average delay in diagnosis for transferred patients was 6.5 days vs. 3.6 days for patients with ureteral injury sustained at WVU. Cystoscopy was only utilized in 37% (10/27) of gynecologic cases involving a ureteral injury. When cystoscopy was utilized, it was 80% (8/10) effective in helping to identify ureteral injury. CONCLUSIONS: Within a rural population, approximately half of patients with ureteral injuries were transferred to a tertiary care center for evaluation and treatment. Transferred patients were more likely to have a delay to diagnosis than patients who had injuries sustained at WVU. The delayed diagnosis patients had comparatively worse outcomes. Gynecologic surgeons working in rural hospitals should be adequately trained to perform diagnostic cystoscopy.

Synthesis and highly potent anti-inflammatory activity of licofelone- and ketorolac-based 1-arylpyrrolizin-3-ones.

Since NSAIDs are commonly used anti-inflammatory agents that produce adverse effects, there have been ongoing efforts to develop more effective and less toxic compounds. Based on the structure of the anti-inflammatory pyrrolizines licofelone and ketorolac, a series of 1-arylpyrrolizin-3-ones was synthesized. Also prepared was a series of substituted pyrroles, mimicking similar known anti-inflammatory agents. The anti-inflammatory activity of the test compounds was determined with a phorbol ester (TPA)-induced murine ear edema protocol. For the most active derivatives, 19b-c/20b-c, the anti-inflammatory effect was the same as that of the reference compound (indomethacin) and was dose-dependent. These compounds have an aryl ring at the C-1 position and a methoxycarbonyl group at the C-2 position of the pyrrolizine framework, which represent plausible pharmacophore groups with anti-inflammatory activity. The anti-inflammatory activity of 1-substituted analogs containing a five- or six-membered heterocycles was lower but still good, while that of the pyrroles was only moderate. Although the docking studies suggests that the effect of analogs 19a-c/20a-c is associated with the inhibition of cyclooxygenase-2, experimental assays did not corroborate this idea. Indeed, a significant inhibition of NO was found experimentally as a plausible mechanism of action.

Subchronic exposure to titanium dioxide nanoparticles modifies cardiac structure and performance in spontaneously hypertensive rats.

BACKGROUND: Non-communicable diseases, intended as the results of a combination of inherited, environmental and biological factors, kill 40 million people each year, equivalent to roughly 70% of all premature deaths globally. The possibility that manufactured nanoparticles (NPs) may affect cardiac performance, has led to recognize NPs-exposure not only as a major Public Health concern, but also as an occupational hazard. In volunteers, NPs-exposure is problematic to quantify. We recently found that inhaled titanium dioxide NPs, one of the most produced engineered nanomaterials, acutely increased cardiac excitability and promoted arrhythmogenesis in normotensive rats by a direct interaction with cardiac cells. We hypothesized that such scenario can be exacerbated by latent cardiovascular disorders such as hypertension. RESULTS: We monitored cardiac electromechanical performance in spontaneously hypertensive rats (SHRs) exposed to titanium dioxide NPs for 6 weeks using a combination of cardiac functional measurements associated with toxicological, immunological, physical and genetic assays. Longitudinal radio-telemetry ECG recordings and multiple-lead epicardial potential mapping revealed that atrial activation times significantly increased as well as proneness to arrhythmia. At the third week of nanoparticles administration, the lung and cardiac tissue encountered a maladaptive irreversible structural remodelling starting with increased pro-inflammatory cytokines levels and lipid peroxidation, resulting in upregulation of the main pro-fibrotic cardiac genes. At the end of the exposure, the majority of spontaneous arrhythmic events terminated, while cardiac hemodynamic deteriorated and a significant accumulation of fibrotic tissue occurred as compared to control untreated SHRs. Titanium dioxide nanoparticles were quantified in the heart tissue although without definite accumulation as revealed by particle-induced X-ray emission and ultrastructural analysis. CONCLUSIONS: The co-morbidity of hypertension and inhaled nanoparticles induces irreversible hemodynamic impairment associated with cardiac structural damage potentially leading to heart failure. The time-dependence of exposure indicates a non-return point that needs to be taken into account in hypertensive subjects daily exposed to nanoparticles.

Spatial bias in figure placement in representational drawing: Associations with handedness and script directionality.

Spatial biases in graphomotor production tasks such as figure drawing may reflect biological (cerebral lateralization), biomechanical (limb movement), and/or cultural (reading/writing direction) influences. The present study examined sources of bias in the placement in graphic space of a symmetrical drawn figure (a tree). A previous study using a child sample found an overall leftward placement bias, independent of participants' reading/writing direction experience [Picard & Zarhbouch, 2014. Leftward spatial bias in children's drawing placement: Hemispheric activation versus directional hypotheses. Laterality: Asymmetries of Body, Brain and Cognition, 19(1), 96-112]; moreover, the left-side bias was greater in right handers. Using an adult sample, the present study also found an overall left placement bias. This effect was significantly greater in right-handed than left-handed participants. Importantly, a left placement bias was significantly greater in left-to-right readers (English) than in participants whose first learned language was from right-to-left (Urdu, Arabic or Farsi). The fact that script directionality is associated with figure placement in our study but not in the previous study suggests that a certain threshold of experience in reading/writing in a given direction may be needed for scanning biases to exert a demonstrable effect on representational drawing. These findings suggest that biomechanical and cultural factors offer a more parsimonious account of spatial biases in drawing.

Knot integrity using different suture types and different knot-tying techniques for reconstructive pelvic floor procedures.

INTRODUCTION AND HYPOTHESIS: Surgeons use a variety of sutures and knot-tying methods during pelvic reconstructive procedures. We hypothesized that knot-strength integrity will be similar with regards to type of knot, type of suture, and the knot-tying process. METHODS: Using six different suture materials, flat square knots and slip knots were tied robotically and by hand by two surgeons. Knot integrity was evaluated using an Instron 5544 machine. We measured force and elongation at suture failure or knot slippage (whichever came first) as well as force at 3-mm displacement. RESULTS: Four hundred and thirty-two knots were tie; one unraveled before the analysis, and 431 were tested. Three hundred and ninety-two knots reached or surpassed tensile strength of 30 N, the force at which tissue itself will fail. Knots tied with polyglyconate suture achieved the greatest tensile strength and those with OO-polydioxanone had the lowest. Hand-tied knots, regardless of technique and suture material, had greater tensile strength but greater elongation than robotically tied knots. Slip knots and flat square knots have similar integrity regardless of the tying technique. CONCLUSION: Hand-tied knots had greater tensile strength than robotic knots, but the strength to break all knots required supraphysiological conditions. The decision to use a specific type of suture based on strength is not supported by our results, suggesting that surgeons may choose sutures based on other characteristics and personal comfort.

Dibutyltin(IV) Complexes Derived from L-DOPA: Synthesis, Molecular Docking, Cytotoxic and Antifungal Activity.

A series of organotin(IV) complexes was herein prepared and characterized. A one-pot synthetic strategy afforded reasonable to high yields, depending on the nature of the ligand. All new complexes were fully characterized by spectroscopic techniques, consisting of IR, MS and NMR (1H, 13C and 119Sn). The in vitro cytotoxicity tests demonstrated that the organotin complexes produced a greater inhibition, versus cisplatin (the positive control), of the growth of six human cancer cell lines: U-251 (glioblastoma), K-562 (chronic myelogenous leukemia), HCT-15 (colorectal), MCF-7 (breast), MDA-MB-231 (breast) and SKLU-1 (non-small cell lung). The potency of this cytotoxic activity depended on the nature of the substituent bonded to the aromatic ring. All complexes exhibited excellent IC50 values. The test compounds were also screened in vitro for their antifungal effect against Candida glabrata and Candida albicans, showing minimum inhibitory concentration (MIC) values lower than those obtained for fluconazole. A brine shrimp bioassay was performed to examine the toxic properties. Molecular docking studies demonstrated that the organotin(IV) complexes bind at the active site of topoisomerase I in a similar manner to topotecan, sharing affinity for certain amino acid side chains (Ile535, Arg364 and Asp533), as well as for similar DNA regions (DA113, DC112 and DT10).

Synthesis, Molecular Docking, and Antimycotic Evaluation of Some 3-Acyl Imidazo[1,2-a]pyrimidines.

A series of 3-benzoyl imidazo[1,2-a]pyrimidines, obtained from N-heteroarylformamidines in good yields, was tested in silico and in vitro for binding and inhibition of seven Candida species (Candida albicans (ATCC 10231), Candida dubliniensis (CD36), Candida glabrata (CBS138), Candida guilliermondii (ATCC 6260), Candida kefyr, Candida krusei (ATCC 6358) and Candida tropicalis (MYA-3404)). To predict binding mode and energy, each compound was docked in the active site of the lanosterol 14α-demethylase enzyme (CYP51), essential for fungal growth of Candida species. Antimycotic activity was evaluated as the 50% minimum inhibitory concentration (MIC50) for the test compounds and two reference drugs, ketoconazole and fluconazole. All test compounds had a better binding energy (range: -6.11 to -9.43 kcal/mol) than that found for the reference drugs (range: 48.93 to -6.16 kcal/mol). In general, the test compounds showed greater inhibitory activity of yeast growth than the reference drugs. Compounds 4j and 4f were the most active, indicating an important role in biological activity for the benzene ring with electron-withdrawing substituents. These compounds show the best MIC50 against C. guilliermondii and C. glabrata, respectively. The current findings suggest that the 3-benzoyl imidazo[1,2-a]pyrimidine derivatives, herein synthesized by an accessible methodology, are potential antifungal drugs.