Highly Soluble Dacarbazine Multicomponent Crystals Less Prone to Photodegradation.

Dacarbazine (DTIC) is a widely prescribed oncolytic agent to treat advanced malignant melanomas. Nevertheless, the drug is known for exhibiting low and pH-dependent solubility, in addition to being photosensitive. These features imply the formation of the inactive photodegradation product 2-azahypoxanthine (2-AZA) during pharmaceutical manufacturing and even drug administration. We have focused on developing novel DTIC salt/cocrystal forms with enhanced solubility and dissolution behaviors to overcome or minimize this undesirable biopharmaceutical profile. By cocrystallization techniques, two salts, two cocrystals, and one salt-cocrystal have been successfully prepared through reactions with aliphatic carboxylic acids. A detailed structural study of these new multicomponent crystals was conducted using X-ray diffraction (SCXRD, PXRD), spectroscopic (FT-IR and 1H NMR), and thermal (TG and DSC) analyses. Most DTIC crystal forms reported display substantial enhancements in solubility (up to 19-fold), with faster intrinsic dissolution rates (from 1.3 to 22-fold), contributing positively to reducing the photodegradation of DTIC in solution. These findings reinforce the potential of these new solid forms to enhance the limited DTIC biopharmaceutical profile.

Intracanal removal and apical extrusion of filling material after retreatment using rotary or reciprocating instruments: A new approach using human cadavers.

AIM: This study compared intracanal removal of filling as well as the frequency and volume of extruded material after retreatment with either HyFlex or Reciproc instruments in mandibular teeth from cadavers. METHODOLOGY: The root canals of 14 pairs of contralateral single-rooted teeth in mandibles of cadavers were instrumented with Reciproc R40 and filled using lateral compaction. The mandibles were scanned in a micro-computed tomographic (micro-CT) device before and after retreatment procedures. The contralateral teeth were assigned to two groups (n = 14) according to the retreatment protocol using either HyFlex or Reciproc instrument systems. In the HyFlex group, the HyFlex Remover instrument was worked 3 mm short of the working length (WL), followed by HyFlex CM 40.04 and 50.04 at the WL. In the Reciproc group, the R50 instrument was worked up at the coronal two thirds, followed by two more cycles until the WL was reached. Pre- and post-operative micro-CT images were analysed for extrusion and intracanal removal of filling material. RESULTS: After retreatment, extrusion of filling material occurred in 11 (78%) and 14 (100%) teeth from HyFlex and Reciproc groups respectively (p > .05). A similar volume of extruded material was observed after retreatment with both systems (p > .05). A significant decrease in the intracanal filling volume was verified after retreatment with both tested systems (p < .05). However, residual filling material was found in all root canals, regardless of the system. The amount of filling material removed (HyFlex = 80.8%; Reciproc = 65.9%) and the operation time was similar between systems (p > .05). CONCLUSIONS: A high frequency of filling material extrusion was observed after retreatment with the two systems in a cadaver model, with no significant difference between them. Both protocols obtained similar efficacy in filling material removal procedures, although none completely cleaned the canals.

[A case of communicating oncocytic carcinoma of the naso-orbit].

A patient with a left eyelid mass for more than 1 year was admitted. One year ago, the patient underwent left sinus mass resection in another hospital, and the postoperative histopathology showed oncocytic carcinoma. Imaging examination in our hospital revealed lesions in the left eyelid and inner canthus, involving the canalis nasolacrimalis and orbit. The orbital mass was removed under general anesthesia. The histopathological diagnosis was oncocytic carcinoma.

Efficacy and Safety of Everolimus Plus Low-Dose Tacrolimus Versus Mycophenolate Mofetil Plus Standard-Dose Tacrolimus in De Novo Renal Transplant Recipients: 12-Month Data.

In this 12-month, multicenter, randomized, open-label, noninferiority study, de novo renal transplant recipients (RTxRs) were randomized (1:1) to receive everolimus plus low-dose tacrolimus (EVR+LTac) or mycophenolate mofetil plus standard-dose Tac (MMF+STac) with induction therapy (basiliximab or rabbit anti-thymocyte globulin). Noninferiority of composite efficacy failure rate (treated biopsy-proven acute rejection [tBPAR]/graft loss/death/loss to follow-up) in EVR+LTac versus MMF+STac was missed by 1.4%, considering the noninferiority margin of 10% (24.6% vs. 20.4%; 4.2% [-3.0, 11.4]). Incidence of tBPAR (19.1% vs. 11.2%; p < 0.05) was significantly higher, while graft loss (1.3% vs. 3.9%; p < 0.05) and composite of graft loss/death/lost to follow-up (6.1% vs. 10.5%, p = 0.05) were significantly lower in EVR+LTac versus MMF+STac groups, respectively. Mean estimated glomerular filtration rate was similar between EVR+LTac and MMF+STac groups (63.1 [22.0] vs. 63.1 [19.5] mL/min/1.73 m2 ) and safety was comparable. In conclusion, EVR+LTac missed noninferiority versus MMF+STac based on the 10% noninferiority margin. Further studies evaluating optimal immunosuppression for improved efficacy will guide appropriate dosing and target levels of EVR and LTac in RTxRs.

Transformation of the CmACS-7 gene into melon (Cucumis melo L.) using the pollen-tube pathway.

The aim of the present study was to develop a transformation system that may be useful for introducing agronomically and biotechnologically relevant traits into melon. The production of transplanted melon with maternal inheritance of the transgene could solve problems related to outcrossing between genetically modified crops and conventional crops or their wild relatives. By analyzing the main influencing factors systematically, the pollination time was ascertained and the pollen-tube pathway genetic transformation system was optimized. A screening system for resistant seeds from the T1 generation was established. The transformed seedlings were grown under standard field conditions and selected using a polymerase chain reaction-based analysis. The resistant plants were detected at a rate of 5%. These results indicate that enhanced production hastens the initiation of bisexual flowers, development of mature bisexual flowers, and fruit set in melon. We have established a melon transformation system based on the pollen-tube method.

Overexpression of the CmACS-3 gene in melon causes abnormal pollen development.

Sexual diversity expressed by the Curcurbitaceae family is a primary example of developmental plasticity in plants. Most melon genotypes are andromonoecious, where an initial phase of male flowers is followed by a mixture of bisexual and male flowers. Over-expression of the CmACS-3 gene in melon plants showed an increased number of flower buds, and increased femaleness as demonstrated by a larger number bisexual buds. Transformation of CmACS-3 in melons showed earlier development of and an increased number of bisexual buds that matured to anthesis but also increased the rate of development of the bisexual buds to maturity. Field studies showed that CmACS-3-overexpressing melons had earlier mature bisexual flowers, earlier fruit set, and an increased number of fruits set on closely spaced nodes on the main stem.

Marker-assisted selection of Fusarium wilt-resistant and gynoecious melon (Cucumis melo L.).

In this study, molecular markers were designed based on the sex determination genes ACS7 (A) and WIP1 (G) and the domain in the Fusarium oxysporum-resistant gene Fom-2 (F) in order to achieve selection of F. oxysporum-resistant gynoecious melon plants. Markers of A and F are cleaved amplified polymorphic sequences that distinguish alleles according to restriction analysis. Twenty F1 and 1863 F2 plants derived from the crosses between the gynoecious line WI998 and the Fusarium wilt-resistant line MR-1 were genotyped based on the markers. The results showed that the polymerase chain reaction and enzyme digestion results could be effectively used to identify plants with the AAggFF genotype in F2 populations. In the F2 population, 35 gynoecious wilt-resistant plants were selected by marker-assisted selection and were confirmed by disease infection assays, demonstrating that these markers can be used in breeding to select F. oxysporum-resistant gynoecious melon plants.

Analysis of microbial diversity and niche in rhizosphere soil of healthy and diseased cotton at the flowering stage in southern Xinjiang.

Understanding how microbial community composition and diversity respond to continuous cropping obstacle is not well understood. However, determining the community composition vs assessing the diversity of molecular operational taxonomic units is often difficult. In this study, we focused on the microbial diversity and niche differentiation in rhizosphere soils between healthy and diseased cotton using a molecular approach based on a culture-independent method. A total of 124 operational taxonomic units (OTUs) from 1076 DNA fragments were detected, including 46, 57, and 21 OTUs from fungi, bacteria, and actinomycetes, respectively. The identified OTUs were confirmed by sequencing after polymerase chain reaction-restriction fragment length polymorphism analysis. The number of OTUs from Fusarium species in diseased rhizosphere soils was higher than that in healthy rhizosphere, which was consistent with field observations. Overall, the results showed that microbes in healthy rhizosphere soils were more diverse and occupied a wider niche in the healthy rhizosphere soil environment of the cotton field. Beneficial microbes should further be analyzed in studies examining the soil ecology of fields in which continuous cropping of cotton takes place.

Molecular tracing of white muscardine in Asian corn borer using inter-simple sequence repeat (ISSR) analysis.

Beauveria bassiana is a soil fungus that parasitizes arthropod species, and is used to control the Asian corn borer in Northeast China. In this study, B. bassiana was investigated in Xiaoxian County and Baicheng City, and the results were compared with those of Gongzhuling City, where the fungus was not applied. Using the inter-simple sequence repeat (ISSR) molecular marker technique, 198 isolates were extracted from Asian corn borer and other insect cadavers, and soil and air, and two released strains were analyzed to trace the infection source. In Xiaoxian and Baicheng populations, artificially released B. bassiana subpopulations were more abundant than indigenous fungi, and the released strains were the main cause of disease in those areas. Artificial B. bassiana displayed positive effect on overwintering of Asian corn borers in corn straw stacks in Xiaoxian County. Indigenous populations in Gongzhuling City showed higher genetic variation. In summary, we identified a significant correlation between genetic distance and geographic distance (P < 0.01).

Fiber-integrated 780 nm source for visible parametric generation.

We report the development of a fully fiber-integrated pulsed master oscillator power fibre amplifier (MOPFA) source at 780 nm, producing 3.5 W of average power with 410 ps pulses at a repetition rate of 50 MHz. The source consists of an intensity modulated 1560 nm laser diode amplified in an erbium fiber amplifier chain, followed by a fiber coupled periodically poled lithium niobate crystal module for frequency doubling. The source is then used for generating visible light through four-wave mixing in a length of highly nonlinear photonic crystal fiber: 105 mW at 668 nm and 95 mW at 662 nm are obtained, with pump to anti-Stokes conversion slope efficiencies exceeding 6% in both cases.

Early hospital readmissions post-kidney transplantation are associated with inferior clinical outcomes.

Unplanned hospital readmissions are common early post-kidney transplantation. We investigated the relationship between early hospital readmissions and clinical outcomes in a single-center retrospective study that included all adult kidney transplant patients between 2004 and 2008 with follow-up to December 2012. The early hospital readmissions within the first 30 d were numbered and the diagnosis ascertained. Patients were grouped as none, once, and twice or more readmissions. Predictors of early readmissions were assessed, and clinical outcomes and patient and death-censored kidney survival were compared. Among 1064 patients, 203 (19.1%) patients had once and 83 (7.8%) patients had twice or more readmissions within 30 d. Surgical complications, infections, and acute kidney injuries/acute rejection were three most common diagnoses. The length of initial hospital stay and African American race were among the variables associated significantly with readmissions. Patients with early readmissions had lower baseline renal function (p < 0.01) and more early acute rejection (p < 0.01). During follow-up, only frequent readmissions, twice or more, within 30 d were associated with increased risk of death (AHR 1.75, p = 0.01) and death-censored kidney failure (AHR 2.20, p < 0.01). Frequent early hospital readmissions post-transplantation identify patients at risk for poor long-term outcomes, and more studies are needed to understand the mechanisms.

An efficient regeneration protocol for Agrobacterium-mediated transformation of melon (Cucumis melo L.).

An efficient selection and plant regeneration protocol for Agrobacterium-mediated transformation, using cotyledon node zone-stem connection region of melon, has been developed. The new Agrobacterium-mediated transformation methodology, independent of organ culture, used the entire germinated seed as explants. The transformation system was maximized to maintain the integrity of melon itself, thus avoiding the limitations of traditional tissue culture methods. The transformation was carried out under a non-sterile environment. The incorporation of a selectable marker (neomycin phosphotransferase II) into the genome of transgenic plants was confirmed by PCR and Southern blot analyses. The transformation frequency based on the PCR was 13%. Transgenic melon plants were usually detected by PCR in less than 1 month after Agrobacterium inoculation, and seeds could be harvested in 3 months. The growth characteristics and morphology of the transgenic plants were identical to the untransformed wild-type plants. This method would be beneficial for facilitating the characteristics of gene functions and for boosting the manipulation of melon transformation for commercial purposes.

Kinetics, mechanism, and tautomerism in ametryn acid hydrolysis: From molecular structure to environmental impacts.

The excessive use of pesticides and the demand for environmentally friendly compounds have driven the focus to detailed studies of the environmental destination of these compounds. Degradation by hydrolysis of pesticides, when released into the soil, can result in the formation of metabolites with potentially adverse effects on the environment. Moving in this direction, we investigated the mechanism of acid hydrolysis of the herbicide ametryn (AMT) and predicted the toxicities of metabolites through experimental and theoretical approaches. The formation of ionized hydroxyatrazine (HA) occurs with the release of the SCH3- group and the addition of H3O+ to the triazine ring. The tautomerization reactions privileged the conversion of AMT into HA. Furthermore, the ionized HA is stabilized by an intramolecular reaction that provides the molecule in two tautomeric states. Experimentally, the hydrolysis of AMT was obtained under acidic conditions and at room temperature with HA as the main product. HA was isolated in a solid state through its crystallization as organic counterions. The mechanism of conversion of AMT to HA and the experimental investigation of the reaction kinetics allowed us to determine the dissociation of CH3SH as the rate-controlling step in the degradation process that culminates in a half-life between 7 and 24 months under typical acid soil conditions of the Brazilian Midwest - region with strong agricultural and livestock vocation. The keto and hydroxy metabolites showed substantial thermodynamic stability and a decrease in toxicity compared to AMT. We hope that this comprehensive study will support the understanding of the degradation of s-triazine-based pesticides.

Impact of cytomegalovirus disease in D+/R- kidney transplant patients receiving 6 months low-dose valganciclovir prophylaxis.

Late-onset cytomegalovirus (CMV) disease remains common in CMV serology naïve kidney transplant patients of CMV serology positive organs (D+/R-) despite the use of antiviral prophylaxis. We studied clinical efficacy of 6-month low-dose valganciclovir (VGCV) prophylaxis, risk factors for late-onset CMV disease and its impact on kidney transplant outcomes. Between October 2005 and December 2009, 166 consecutive D+/R- kidney alone and simultaneous pancreas and kidney transplant patients received VGCV 450 mg daily for 6 months after transplantation. After a median follow-up of 3.2 years, 30 cases of CMV disease occurred within the first 2 years after transplantation with a cumulative incidence of 11.5 and 18.1% at 1 and 2 years, respectively. The use of an induction agent with rabbit antithymocyte globulin and older donor age were factors associated with the risk of late-onset CMV disease (AHR 2.91, 95% CI 1.18-7.20, p = 0.021 and AHR 1.03, 95% CI 1.01-1.06, p = 0.016, respectively). Late-onset CMV disease was associated with increased risk for death-uncensored graft loss (AHR 2.95, 95% CI 1.15-7.61, p = 0.025). In conclusion, late-onset CMV disease continues to negatively impact kidney transplant outcome despite 6-month low-dose VGCV prophylaxis. Investigations focusing on novel preventive approaches should be emphasized.

Preliminary efficiency evaluation of development methods applied to aged sebaceous latent fingermarks.

Latent fingermarks are important trace evidence found in crime scenes mainly used for identification purposes. Once deposited, the composition of samples changes over time influencing the efficacy of latent fingermark development methods. In this sense, the aims of this work were to characterize the fatty acid (FA) profile of sebaceous latent fingermarks by GC-FID and to preliminarily evaluate the development efficiency of enhancement methods (powder dusting, iodine fuming and silver nitrate method) in a 30-day period of aging under controlled parameters of temperature, photoperiod and humidity. Results showed that myristic (7.51 ± 0.76% - 13.39 ± 1.26%), palmitic (35.91 ± 1.07% - 40.81 ± 2.52%), stearic (6.67 ± 0.36% - 9.13 ± 0.36%) and oleic (18.08 ± 0.25% - 20.93 ± 0.26%) acid varied significantly (p < 0.05) over the 30-day period of analysis. Regarding development efficiency, fluorescent orange powder and the silver nitrate method also increased their efficacy to develop latent fingermarks over time while the iodine fuming method decreased its efficiency. Silver black powder had constant efficacy in the tested period. Changes in the constitution of sebaceous marks possibly influenced the development efficiency of enhancement techniques. This knowledge is important to better understand the kinetic of aging and its influence on the development method.

[Distribution characteristics of blood pressure in Hainan centenarians].

Objective: To explore the blood pressure levels and the influencing factors of hypertension among Hainan centenarians, and provide basic data for the further blood pressure related studies of the centenarian population. Methods: The baseline data were from China Hainan Centenarian Cohort Study (CHCCS). This cross-sectional data, based on the community population, was a complete sample study of centenarians, including questionnaire survey, physical examination and physiological index detection. A total of 1 002 centenarians were recruited to describe the blood pressure level. According to the guidelines for the prevention and treatment of hypertension in Chinese adults in 2018, the prevalence of hypertension was analyzed. Results: The median levels of systolic blood pressure, diastolic pressure and pulse pressure were 152.0, 76.0 and 76.5 mmHg, respectively. Blood pressure level was higher in females than in males. The prevalence of hypertension was 71.9%, mainly in isolated systolic hypertension with the prevalence of 60.1%. The results of multivariate analysis showed that the risk of hypertension in women was higher than that in men (OR=1.624, 95%CI: 1.155-2.283), and the risk of hypertension in the northern (OR=0.625, 95%CI: 0.434-0.901) and central areas (OR=0.586, 95%CI: 0.346-0.993) was lower than that of the Eastern. Conclusion: The prevalence of hypertension, mainly in isolated systolic hypertension, showing gender and regional distribution differences.

Pattern-Reversal Visual Evoked Potential in Children With Congenital Zika Syndrome.

PURPOSE: To objectively evaluate the visual function in children with congenital Zika syndrome using pattern-reversal visual evoked potential (PR-VEP). METHODS: This was a cross-sectional study composed of two patient groups: children aged between 18 and 24 months who were positive for the Zika virus (congenital Zika syndrome group) and age-matched healthy children (control group). All patients underwent a comprehensive ophthalmologic examination and PR-VEP was performed binocularly in a room with constant dim illumination. The P100 peak time in the 60' arc stimuli was used, and the results were correlated with visual acuity, cephalic perimeter at birth, and funduscopic findings. RESULTS: Thirty-seven children were included in the congenital Zika syndrome group and 15 in the control group. The mean age was 18.5 ± 0.9 months (range: 17 to 20 months) in the congenital Zika syndrome group and 24.3 ± 1.6 months (range: 21 to 28 months) in the control group. The P100 response was normal in 7 patients (18.9%) with congenital Zika syndrome, borderline in 2 (5.4%), abnormal with prolonged latency in 18 (48.6%), and abnormal with no response in 10 (27.0%). A significant correlation between the visual acuity and P100 peak time was observed (P < .001). The P100 values were not correlated significantly with the cephalic perimeter at birth (P = .412) or the funduscopic findings (P = .510). PR-VEP in children with congenital Zika syndrome and no funduscopic findings was significantly worse than in the control group (P = .001). CONCLUSIONS: Children with congenital Zika syndrome have characteristically abnormal PR-VEPs regardless of the funduscopic findings and severe microcephaly. The PR-VEP findings supported the diagnosis of cortical visual impairment in these children. [J Pediatr Ophthalmol Strabismus. 2021;58(2):78-83.].

Multicomponent ionic crystals of diltiazem with dicarboxylic acids toward understanding the structural aspects driving the drug-release.

Diltiazem (DIL) is a calcium channel blocker antihypertensive drug commonly used in the treatment of cardiovascular disorders. Due to the high solubility and prompt dissolution of the commercial form hydrochloride (DIL-HCl) that is closely related to short elimination drug half-life, this API is known for exhibiting an unfitted pharmacokinetic profile. In an attempt to understand how engineered multicomponent ionic crystals of DIL with dicarboxylic acids can minimize these undesirable biopharmaceutical attributes, herein, we have focused on the development of less soluble and slower dissolving salt/cocrystal forms. By the traditional solvent evaporation method, two hydrated salts of DIL with succinic and oxalic acids (DIL-SUC-H2O and DIL-OXA-H2O), and one salt-cocrystal with fumaric acid (DIL-FUM-H2FUM) were successfully prepared. An in-depth crystallographic description of these new solid forms was conducted through single and powder X-ray diffraction (SCXRD, PXRD), Hirshfeld surface (HS) analysis, energy framework (EF) calculations, Fourier Transform Infrared (FT-IR) spectroscopy, and thermal analysis (TG, DSC, and HSM). Structurally, the inclusion of dicarboxylic acids in the crystal structures provided the formation of 2D-sheet assemblies, where ionic pairs (DIL+/anion-) are associated with each other via H-bonding. Consequently, a substantial lowering in both solubility (16.5-fold) and intrinsic dissolution rate (13.7-fold) of the API has been achieved compared to that of the hydrochloride salt. These findings demonstrate the enormous potential of these solid forms in preparing of novel modified-release pharmaceutical formulations of DIL.

Influence of recipient race on the outcome of simultaneous pancreas and kidney transplantation.

Racial differences on the outcome of simultaneous pancreas and kidney (SPK) transplantation have not been well studied. We compared mortality and graft survival of African Americans (AA) recipients to other racial/ethnic groups (non-AA) using the national data. We studied a total of 6585 adult SPK transplants performed in the United States between January 1, 2000 and December 31, 2007. We performed multivariate logistic regression analyses to determine risk factors associated with early graft failure and immune-mediated late graft loss. We used conditional Kaplan-Meier survival and multivariate Cox regression analyses to estimate late death-censored kidney and pancreas graft failure and death between the groups. Although there was no racial disparity in the first 90 days, AA patients had 38% and 47% higher risk for late death-censored kidney and pancreas graft failure, respectively (p = 0.006 and 0.001). AA patients were twice more likely to lose the kidney and pancreas graft due to rejection (OR 2.31 and 1.86, p = 0.002 and 0.008, respectively). Bladder pancreas drainage was associated with inferior patient survival (HR 1.42, 95% CI 1.15, 1.75, p = 0.001). In the era of modern immunosuppression, AA SPK transplant patients continue to have inferior graft outcome. Additional studies to explore the mechanisms of such racial disparity are warranted.

Optical phase conjugation by an As(2)S(3) glass planar waveguide for dispersion-free transmission of WDM-DPSK signals over fiber.

We report the first demonstration of optical phase conjugation (OPC) transmission of phase encoded and wavelength-division multiplexed (WDM) signals by the Kerr effect in a planar structured waveguide. The phase conjugated electric field of the signal is produced by four wave mixing pumped by a CW laser during co-propagating with the signal in a highly nonlinear waveguide fabricated in As(2)S(3) glass. Experiments demonstrate the capability of the device to perform dispersion-free transmission through up to 225 km of standard single mode fiber for a 3 × 40 Gb/s WDM signal, with its channels encoded as return-to-zero differential phase shift keying and spaced either 100 or 200 GHz apart. This work represents an important milestone towards demonstrating advanced signal processing of high-speed and broadband optical signals in compact planar waveguides, with the potential for monolithic optical integration.