Silver nanoparticles, a promising treatment against clinically important fluconazole-resistant Candida glabrata.

Resistance to azole antifungal agents is a challenging limitation in Candida glabrata treatment. It is associated with decreased intracellular concentrations of antifungal agents as a result of overexpression of efflux pumps on the cellular plasma membranes. This work evaluates the potential of silver nanoparticles (AgNPs) to reverse the resistance of fungal cells to fluconazole. Silver nanoparticles were prepared using wet chemical method and characterised by UV-Vis spectrophotometry, dynamic light scattering, and zeta potential. Broth microdilution and pour plates methods were used to study the anticandidal activity using two C. glabrata fluconazole-resistant strains (DSY565 and CBS138) known to overexpress active efflux pumps, and a standard fluconazole sensitive strain ATCC 22553. Silver nanoparticles-fluconazole combinations decreased concentrations of fluconazole substantially without compromising the activity. These findings suggest that AgNPs enhance the efficacy of fluconazole and offer a promising application in therapy of C. glabrata infections.

Correction to: Cesarean delivery to prevent anal incontinence: a systematic review and meta-analysis.

The original article can be found online.

Cesarean delivery to prevent anal incontinence: a systematic review and meta-analysis.

BACKGROUND: Cesarean delivery (CD), is increasingly recommended as a mode of delivery that prevents the anal incontinence (AI) that arises in some women after vaginal delivery (VD). The assessment of the efficacy of CD in this regard was the subject of this systematic review. METHODS: Searches were conducted in Medline, EMBASE and the Cochrane Library. Both randomized (RCTs) and non-randomized trials (NRTs) comparing the risk of sustained fecal and/or flatus incontinence after VD or CD were sought from 1966 to 1 January, 2019. Studies were eligible if they assessed AI more than 6 months after birth, and had statistical adjustment for at least one of the three major confounders for AI: age, maternal weight or parity. In addition, each study was required to contain more than 250 participants, more than 50 CDs and more than 25 cases of AI. Data after screening and selection were abstracted and entered into Revman for meta-analysis. Analyses were done for combined fecal and flatus incontinence (comAI), fecal incontinence (FI), gas incontinence (GI), CD before or during labor, time trend of incontinence after delivery, assessment of both statistical and clinical heterogeneity, parity and late incident AI. RESULTS: Out of the 2526 titles and abstracts found, 24 eligible studies were analyzed, 23 NRTs and one RCT. These included women with 29,597 VDs and women with 6821 CDs. Among the primary outcomes, VD was found not to be a significant predictor of postpartum comAI compared to CD in 6 studies, incorporating 18,951 deliveries (OR = 0.74; 0.54-1.02). VD was also not a significant predictor of FI in 14 studies, incorporating 29,367 deliveries, (OR = 0.89; 0.76-1.05). VD was not a significant predictor of GI in six studies, incorporating 6724 deliveries (OR = 0.96; 0.79-1.18). The strength of the grading of recommendations, assessment, development and evaluations (GRADE) evidence for each of these was low for comAI and moderate for FI and GI (upgrade for lack of expected effect). Time trend FI showed incontinence at 3 months often resolved at 1 year. Other secondary analyses assessing parity, delayed incidence of FI, clinical and statistical heterogeneity, spontaneous VD only, late risk of incidence of AI, and CD in or prior to labor all had similar results as in the primary outcomes. CONCLUSIONS: There are three components of pelvic floor dysfunction that are thought to be caused by VD and hopefully prevented by CD: AI, urinary incontinence and pelvic floor prolapse. Of these, AI was not found to be reliably prevented by CD in this review.

Development of a transmission alpha particle dosimetry technique using A549 cells and a Ra-223 source for targeted alpha therapy.

PURPOSE: In targeted radionuclide therapy, regional tumors are targeted with radionuclides delivering therapeutic radiation doses. Targeted alpha therapy (TAT) is of particular interest due to its ability to deliver alpha particles of high linear energy transfer within the confines of the tumor. However, there is a lack of data related to alpha particle distribution in TAT. These data are required to more accurately estimate the absorbed dose on a cellular level. As a result, there is a need for a dosimeter that can estimate, or better yet determine the absorbed dose deposited by alpha particles in cells. In this study, as an initial step, the authors present a transmission dosimetry design for alpha particles using A549 lung carcinoma cells, an external alpha particle emitting source (radium 223; Ra-223) and a Timepix pixelated semiconductor detector. METHODS: The dose delivery to the A549 lung carcinoma cell line from a Ra-223 source, considered to be an attractive radionuclide for alpha therapy, was investigated in the current work. A549 cells were either unirradiated (control) or irradiated for 12, 1, 2, or 3 h with alpha particles emitted from a Ra-223 source positioned below a monolayer of A549 cells. The Timepix detector was used to determine the number of transmitted alpha particles passing through the A549 cells and DNA double strand breaks (DSBs) in the form of γ-H2AX foci were examined by fluorescence microscopy. The number of transmitted alpha particles was correlated with the observed DNA DSBs and the delivered radiation dose was estimated. Additionally, the dose deposited was calculated using Monte Carlo code SRIM. RESULTS: Approximately 20% of alpha particles were transmitted and detected by Timepix. The frequency and number of γ-H2AX foci increased significantly following alpha particle irradiation as compared to unirradiated controls. The equivalent dose delivered to A549 cells was estimated to be approximately 0.66, 1.32, 2.53, and 3.96 Gy after 12, 1, 2, and 3 h irradiation, respectively, considering a relative biological effectiveness of alpha particles of 5.5. CONCLUSIONS: The study confirmed that the Timepix detector can be used for transmission alpha particle dosimetry. If cross-calibrated using biological dosimetry, this method will give a good indication of the biological effects of alpha particles without the need for repeated biological dosimetry which is costly, time consuming, and not readily available.

Jaundice, phototherapy and DNA damage in full-term neonates.

OBJECTIVE: Phototherapy is the standard therapeutic approach for neonatal hyperbilirubinemia. Oxidative effects of phototherapy may have potential harms, including DNA damage. Unconjugated bilirubin (UCB) might also possess antigenotoxic potential. Intensive phototherapy is more efficacious than conventional phototherapy in treating hyperbilirubinemia. This study aimed to assess the impact of hyperbilirubinemia and the two different types of phototherapy on DNA damage in peripheral blood mononuclear cells of neonates. STUDY DESIGN: The study was conducted on term neonates with non-hemolytic hyperbilirubinemia and control healthy neonates. Genotoxicity was assessed using single-cell gel electrophoresis (Comet assay) in peripheral mononuclear cells. Blood samples were obtained at enrollment in all infants and after intensive or conventional phototherapy in jaundiced infants. RESULT: DNA damage did not significantly differ between jaundiced and non-jaundiced neonates (11.4±8.7 and 10.9±8.3 arbitrary units (AU), respectively, P=0.58). It increased significantly after exposure to phototherapy compared with prephototherapy values (45.6±14.7 vs 11.4±8.7 AU, respectively, P<0.001). The duration of phototherapy correlated positively with markers of DNA damage (r=0.86, P<0.001); however, the intensity of used light did not significantly impact genotoxicity. CONCLUSION: Hyperbilirubinemia does not influence DNA damage, whereas both conventional and intensive phototherapy are associated with DNA damage in term infants with hyperbilirubinemia.

Breed and experience effect on the sexual behaviors of Damascus and Egyptian-Nubian goat bucks.

This study compares the sexual behaviors of bucks from two pure breeds of goats, Damascus and Egyptian-Nubian (Zaraibi), and assesses their relationships with the pregnancy and kidding rates of their inseminated does. Twenty-three bucks (12 Damascus and 11 Egyptian-Nubian bucks) were used in this study. These bucks were either in their first season of service (N =12, with an average age of 1.51 years) or had been previously used in service for several seasons (N = 11, with an average age of 3.34 years). Buck service behaviors toward estrous does were continuously recorded for 30 minutes from the moment of appearance of the doe. Egyptian-Nubian bucks were highly sexually active with estrous does in comparison with Damascus bucks. They required less time to mount and ejaculate for the first (P < 0.04) and second times (P < 0.0002) and tended to sniff, nudge and vocalize more frequently than Damascus bucks. In addition, Egyptian-Nubian bucks had more ejaculations and a higher mating efficiency (27.48% vs. 10.21%, P < 0.001), and their inseminated does had a higher pregnancy rate and larger litter sizes. Regarding the effect of experience, the data revealed a limited influence. No significant differences in sexual behavior were recorded between younger and older bucks. Conversely, pregnancy, kidding rates, and litter size were not influenced by the total number of ejaculations. From these results, it can be concluded that there were sexual behavior differences as a function of breed between Damascus and Egyptian-Nubian bucks and that experience had little impact in this study.

The impact of lambing stress on post-parturient behaviour of sheep with consequences on neonatal homeothermy and survival.

During lambing the expression of an appropriate behavioural response from both the ewe and the lamb are extremely important to lamb survival. The aim of this study was to show the effect of length and difficulty of the birth process on the expression of maternal and neonatal behaviour with consequences on homeothermy and survival of the neonate lamb. Data were collected from 61 Finnish Landrace × Rahmani crossbred (second generation) primiparous ewes and their single born lambs. Based on the average length of parturition, the ewes were grouped into short birth (less than 32.5 min) and long birth (equal to or higher than 32.5 min) classes. The data recorded include maternal and neonatal behaviour, lamb body temperature over the first 3 days of life and survival rate of the neonate lamb during the first week after birth. Blood samples were also collected from the lamb, pre-suckling and at 24 and 72 h after birth. The obtained sera were assayed for thyroid hormones (T(3) and T(4)) that are associated with heat production. Ewes that had prolonged and difficult births did not show competent maternal behaviour compared to mothers with short and un-complicated deliveries, as they were slower to begin grooming their lambs after birth, spent less time licking their lambs, made less low-pitched vocalizations and nosing, were more likely to show rejection behaviour (10.34 % vs 5.4 %, P < 0.05), and were more likely to move away when the lamb sought the udder in an attempt to suck (acceptance rate, 55.5 % vs 64.79 %, P < 0.05). Similarly, lambs from a prolonged and difficult birth were significantly less vigorous after birth, as they had taken more time to stand, reach the udder and to suck successfully. These lambs had lower serum concentrations of T(3) and T(4), and they also had a reduced ability to maintain body temperature after birth. This effect persisted over the first 3 days of life and was associated with higher neonatal mortality in the first week after birth (11.54 %), compared to lambs from short and non-stressful birth processes (2.86 %, P < 0.01). From the present study, it can be concluded that, prolonged deliveries with birthing difficulty were one of the main causes of death of large, single-born lambs, as these complications cause the expression of inappropriate behavioural responses from both the ewe and neonatal lamb. Thus, interventions designed to reduce the incidence of prolonged parturitions are likely to be associated with better welfare for the ewe and the lamb and consequently improved lamb homeothermy and survival.

Hemodynamic instability during treatment of intracranial dural arteriovenous fistula and carotid cavernous fistula with Onyx: preliminary results and anesthesia considerations.

BACKGROUND AND AIM: 9 patients with 10 arteriovenous fistulas were treated with Onyx at our institution over a period of 19 months: 4 direct and indirect carotid-cavernous fistulas (CCFs) and 6 dural arteriovenous fistula (DAVFs). Complete occlusion was achieved with no recurrences or permanent complications in our small series. We report hemodynamic instability, including severe bradycardia and asystole, during embolization of DAVF and CCF with Onyx in several patients. These changes were reversible with interruption of Onyx injection and administration of atropine. No recurrence of symptoms after atropine administration was noted as Onyx embolization continued during the same session or during postprocedural 24 h monitoring. No adverse clinical consequences were noted. RESULTS: Bradycardia was observed in 4 cases, with a brief asystole in 2 of these patients during transarterial and transvenous Onyx delivery at cavernous sinus and orbital levels. Based on our observation, hemodynamic instability was demonstrated during Onyx injection into the vessels that were in close proximity to the trigeminal nerve or its branches, especially in low-flow/low-volume compartment and may represent a direct effect of dimethyl sulfoxide/Onyx on the trigeminal nerve, resulting in vagal response from trigeminocardiac reflex. CONCLUSION: Proposed measures to prevent this complication include pretreatment with atropine or prophylactic placement of transvenous pacemakers in patients with underlying heart block and patients with contraindications to atropine use.

Embolization of a Cavernous Sinus Dural Arteriovenous Fistula with Onyx via Direct Puncture of the Cavernous Sinus through the Superior Orbital Fissure: Asystole Resulting from the Trigeminocardiac Reflex. A Case Report.

SUMMARY: Treatment of cavernous sinus dural arteriovenous fistula (CSDAVF) may be challenging.We describe a patient who had presented with progressive ocular symptoms due to CSDAVF requiring urgent interventional therapy. Initial attempts to embolize the fistula utilizing a transvenous approach through the inferior petrosal sinus failed because of difficult anatomy. Successful occlusion of the fistula was subsequently achieved with injection of ethylene vinyl alcohol copolymer, Onyx (EV3 Neurovascular, Irvine, CA, USA), via direct percutaneous puncture of the cavernous sinus through the superior orbital fissure.A brief period of asystole during the initial injection of Onyx may be the result of the trigeminocardiac reflex.

Treatment of arteriovenous malformations with hydrocoils in a Swine model.

SUMMARY: Arteriovenous malformations (AVM) of the brain are the most common symptomatic congenital vascular malformation of the central nervous system, with significant associated morbidity and mortality. This study compared the feasibility and efficacy of treating AVMs by embolization with hydrocoils with similar treatment with bare platinum coils, using the swine rete mirabile as a model. A right carotid-jugular fistula was created in ten swine.A microcatheter was positioned into the rete mirabile, which was unilaterally (contralateral to the fistula) embolized with hydrocoils in six and bare platinum coils in four swine. Angiograms were evaluated during and immediately after embolization. Embolization with complete cessation of bloodf low in the unilateral rete mirabile was achieved in all animals treated with hydrocoils. The number of coils needed varied from four to seven (diameter 2-4 mm; mean coil length 22.3 cm). Embolization with platinum coils of similar number (seven) and slightly longer length (mean 37.75 cm) had a minimal effect on blood flow, resulting in occlusion of only small compartments. No immediate complications were noted with either coil. Hydrocoils are more effective in achieving embolization than bare platinum coils. Expansion of the hydrocoil over only a few minutes allows precise placement and stabilization of the coil before detachment. Hydrocoilscan be safely placed into small vessels. This approach may be particularly useful to decrease the flow rate, as a first stage of AVM embolizationin high flow AVMs that contain arteriovenous fistulae.

Evaluation of dental waste management in two cities in Palestine.

Disposal of dental waste was investigated at 37 randomly selected clinics in Ramallah and AI-Bireh cities: 31 private practices and 6 public/NGO clinics. Dentists were interviewed regarding their disposal of different forms of dental waste. Disinfectants and X-ray processing solution were thrown down the drain. For sharps, 13.5% of dentists used puncture-resistant containers (only in the public/ NGO clinics), 45.9% discarded needles directly in the garbage after being recapped and 40.5% placed the used needles and blades in closed plastic bottles before throwing in the general garbage. Blood-soaked dressings and amalgam waste were also thrown in the garbage. While 10.75% of dentists were vaccinated against hepatitis B, 47% of the staff at private clinics were not.

Evaluation of dental waste management in two cities in Palestine

Disposal of dental waste was investigated at 37 randomly selected clinics in Ramallah and Al-Bireh cities: 31 private practices and 6 public/NGO clinics. Dentists were interviewed regarding their disposal of different forms of dental waste. Disinfectants and X-ray processing solution were thrown down the drain. For sharps, 13.5% of dentists used puncture-resistant containers [only in the public/ NGO clinics], 45.9% discarded needles directly in the garbage after being recapped and 40.5% placed the used needles and blades in closed plastic bottles before throwing in the general garbage. Blood-soaked dressings and amalgam waste were also thrown in the garbage. While 10.75% of dentists were vaccinated against hepatitis B, 47% of the staff at private clinics were not

The effects of some formulation factors used in ophthalmic preparations on thiomersal activity against Pseudomonas aeruginosa and Staphylococcus aureus.

AIMS: To investigate the effects of formulation ingredients used in ophthalmic preparations on thiomersal activity against Staphylococcus aureus and Pseudomonas aeruginosa. METHODS AND RESULTS: Minimum inhibition concentrations (MICs) of the tested ingredients and their combinations were studied using partial broth dilution checkerboard method. Complex formation was determined using differential scanning calorimetry (DSC) and u.v. scan. Isotonic agents showed insignificant difference in thiomersal activity. Low concentrations of propylene glycol and glycerol (2 to about 6.5%) significantly reduced the activity of thiomersal against P. aeruginosa. Higher concentrations up to about 40%, of the two cosolvents did not affect the antibacterial activity. Viscosity increasing agents significantly reduced the antibacterial activity of thiomersal. Low concentrations of 0.05% and 0.05-0.1% of ethylenediaminetetraacetic acid resulted in a significant decrease in thiomersal activity against S. aureus and P. aeruginosa, respectively. However, concentrations above 0.25 and 0.5 up to 4% caused significant increase on the antibacterial activity against the two later micro-organisms, respectively. CONCLUSIONS: Results showed that thiomersal formed complexes with ingredients containing polyhydroxy groups and chelating agents, thus thiomersal is not recommended to be used with such ingredients. SIGNIFICANCE AND IMPACT OF THE STUDY: This study highlighted the importance of proper selection of ingredients and preservatives for ophthalmic preparations.

Screening of antibiotic resistant inhibitors from local plant materials against two different strains of Pseudomonas aeruginosa.

The methanolic extracts of 19 Jordanian plants were combined with seven different antibiotics and applied to check the inhibitory effects of the combination on the resistance of Pseudomonas aeruginosa. A resistant strain of Ps. aeruginosa, which was isolated from a patient and a standard strain of the same microorganism were used in this study. Our results showed that there are significant variations in the effects of some combinations used on the resistant and the standard strains probably due to structural changes. Almost all the plant materials used in combination with penicillin G and erythromycin allowed full growth of the standard strain, while the combination with some plant materials like Gundelia tournefortii L. and Lepidium sativum L. inhibited the growth of the resistant strain. Chloramphenicol, gentamicin and cephalosporin can be given advantageously with almost all the plant materials used with few exceptions on the resistant strain. Nalidixic acid activity was improved significantly when combined with all plant materials and tested on standard strain. On the other hand, its activity on the resistant strain was slightly improved using the same combinations.

Evaluation of an enrofloxacin-treatment program against Mycoplasma gallisepticum infection in broilers.

Three chicken broiler breeder flocks, 7 months of age, were confirmed to have Mycoplasma gallisepticum (MG) infection, based on culture of tracheal swabs. A total of fifty-five 7-day-old embryos from the three MG-positive flocks had an average 27.4% prevalence of MG-infection in their vitelline membrane. Sixty randomly selected MG isolates (30 from individual tracheas of breeders and another 30 from individual vitelline membrane of embryos) were highly sensitive in vitro to enrofloxacin (100%). Three broiler flocks (averaging 15,000 birds per flock) from the same three MG-infected chicken boiler breeders were divided into halves. The first halves were subjected to an enrofloxacin-treatment program and the other halves were controls. Sera collected at different ages of the broiler flocks were tested by the enzyme-linked immunosorbent assay for antibodies to MG. The absence of MG titers at 45 days of age in birds subjected to the enrofloxacin-preventive program was compared to an average prevalence of 15.9% in the controls (p < 0.05). The lack of MG titers in 45-day-old birds subjected to the enrofloxacin-treatment program was associated with lower better feed-conversion ratios (p < 0.05).

Giardia lamblia and chronic gastritis.

One hundred and two patients suffering from giardiasis and/or chronic gastritis were subjected for upper gastrointestinal endoscopy. Purified immune rabbit's serum against Giardia lamblia was used in ELISA and immunoperoxidase (IIP) techniques for detection of Giardia antigen in the stomach. Results showed that out of 70 cases with intestinal giardiasis, 8 (11.4%) by ELISA and 6 (8.6%) by IIP showed gastric giardiasis. Higher percentage of gastric giardiasis (14%) was encountered in cases with both giardiasis and chronic gastritis (50) than in cases with giardiasis alone (5%) but with statistically insignificant difference (P > 0.05). None of the cases with chronic gastritis alone (without giardiasis) was positive for gastric giardiasis. Dyspepsia was the main presenting symptom in cases with gastric giardiasis (P < 0.05) with significant (P < 0.05) association. Helicobacter pylori was encountered in 6 out of 8 cases (75%) with gastric giardiasis (P < 0.05) with significant (P < 0.05) association. Duodenogastric reflux was detected in 4 out of 8 cases (50%). Histopathological changes in antral mucosa were detected in all cases of gastric giardiasis. This study indicates that under abnormal circumstances most probably with decreased gastric acidity, gastric giardiasis can occur in concomitance with intestinal giardiasis. So, one has to search for Giardia in gastric biopsies, particularly those showing chronic atrophic gastritis and H. pylori. Also, one has to be aware of gastric giardiasis as a possible cause of upper gastrointestinal symptoms.

Immunization against Trichinella spiralis using antigens from different life-cycle stages experimental study in mice.

Crude antigen preparations from different life-cycle stages of T. spiralis using 10 micrograms and 100 micrograms antigen/dose, were tested for their ability to immunize mice against homologous challenge infection. Immunization was assessed by accelerated expulsion of adult worms, reduction in female worm fecundity and decreased yield of muscle larvae. The dose of 100 micrograms proved to be more protective in all antigen preparations. The AA provided highly significant protection against adult stages (89%) and muscle larvae (80%). NLA produced highly significant protection against muscle larvae only (76%). MLA provided highly significant protection against adult stages (74%), female fecundity (74%) and muscle larvae (80%). Combination of AA and MLA produced highly significant protection against adult stages (96%), female fecundity (73%) and muscle larvae (86). The results show that all antigen preparations provided variable, considerable but partial protection against challenge infection. The variations in immunization potential are discussed.

Detection of Pneumocystic carinii in immuno-suppressed rats by different histological stains and immunological assays.

Detection of P. carinii in lung sections of 35 immuno-suppressed albino rats was evaluated using five histological stains (toluidine blue "O", Giemsa, Gram's stain, PAS and H & E) and two immunological assays (indirect immunofluorescence [IIF],, and indirect immunoperoxidase [IIP]) using polyclonal antibody, raised in white New Zealand rabbits, against rat P. carinii. In spite of the high sensitivity of the histological stains, they yield hazy details insufficient for easy identification with difficult interpretation. However, Gram and PAS stains provided a better visualization with easy identification of the parasite. On the other hand, both immunological assays allowed an accurate rapid interpretation of the stained slides. The IIP technique, having 100% sensitivity in detecting the precipitated parasite antigens with absolute specificity, seems to be a good diagnostic tool for detecting P. carinii in lung sections.

The hemodynamic effects of isoflurane before and after sternotomy in patients undergoing coronary artery bypass grafting.

The hemodynamic effects of isoflurane were studied in 30 patients undergoing coronary artery bypass grafting, and receiving high dose of fentanyl (40 micrograms/kg). In 15 patients, isoflurane 2% was administered for ten minutes before sternotomy, while the same concentration of isoflurane was administered in the other 15 patients after sternotomy for the same interval of time. Isoflurane administration before sternotomy produced a significant decrease in cardiac index and mean arterial pressure, without a significant change in systemic vascular resistance or other hemodynamic variables. On the other hand, when isoflurane was used to counteract sternotomy-induced hypertension, it produced a significant decrease of systemic vascular resistance, associated with a significant increase in cardiac index.