Impact of haemodialysis on plasma carnitine concentrations in haemodialysis patients.

Objective: To evaluate the impact of haemodialysis on plasma carnitine levels. METHODS: The cross-sectional study was conducted from April 20, 2020 to May 10, 2022, at the dialysis unit of the nephrology ward of Jinnah Postgraduate Medical Centre, Karachi, and the Pakistan Navy Ship Shifa Hospital, Karachi, in collaboration with the Department of Biochemistry, University of Karachi, and comprised patients of either gender aged >18 years. They were divided into chronic kidney disease group A and end-stage renal disease group B. Control group C included subjects from the general population. Free carnitine and total carnitine values were detected using enzyme-linked immunosorbent assay. Acyl carnitine was estimated by applying the standard formula, and the ratio between acyl carnitine and free carnitine was calculated for accurate assessment of the carnitine status. Data was analysed using SPSS 23. RESULTS: Of the 203 subjects, 143(70.44%) were cases and 60(29.55%) were controls. Among the cases, 120(84%) were recruited from Jinnah Postgraduate Medical Centre and 23(16%) from Pakistan Navy Ship Shifa Hospital. There were 60(29.55%) patients in group A, 83(40.88%) in group B and 60(29.55%) in group C. The mean age in group A was 47.90 5.±65 years, it was 44.10 ±8.92 years in group B and 40.90 ± 6.73 years in group C. There was a significant difference related to free carnitine, total carnitine, acyl carnitine values and the ratio between acyl carnitine and free carnitine values in groups A and B compared to control group C (p<0.05). Conclusion: Patients on maintenance haemodialysis developed were found to have developed carnitine deficiency.

The Association of HLA Alleles and Haplotypes with Age of Disease Onset in Pakistani Psoriatic Patients.

INTRODUCTION: The human leukocyte antigen (HLA) region on chromosome 6p21 is well known to carry the most important genetic factors in susceptibility to psoriasis. Different HLA alleles and haplotypes have been reported to be associated with psoriasis in different populations. Psoriasis has a variable age of onset and, based on this, it can be classified into two types; type I with age of onset before 40 years of age and type II with age of onset after 40 years of age. The objective of this study was to determine the association of HLA class I and class II alleles and haplotypes with disease and stratification using age of onset in Pakistani psoriatic patients. METHODS: A group of 603 individuals (326 cases and 277 controls) were analyzed for HLA class I and II alleles and haplotype association by sequence specific PCR. The association was further analyzed according to the age of onset of the patients. RESULTS: We found that HLA alleles B*57 and Cw*06:02, DQB1*03:03:02 are strongly associated with early onset psoriasis, while alleles B*15, DRB1*13:02 and DQB1*03:03:02 are associated with late-onset psoriasis. Cw*06:02 allele was not associated with late-onset psoriasis patients. Allele DQB1*03:03:02 had the highest odds ratio in all patients. We found a novel association specifically with late-onset psoriasis samples with the haplotype HLA-A*11; B*15; Cw*04; DRB1*15; DQB1*05 (Pc = 3.60 × 10-7). We also found strong association with previously reported extended haplotype EH-57.1: HLA-B*57; Cw*06:02; DRB1*07:01; DQB1*03:03:02 in all our patients (Pc = 8.34 × 10-07). CONCLUSION: Our results show that different HLA class I and II alleles and haplotypes are associated with psoriasis at different age of onset. In this study, we have reported novel alleles and haplotype association with late-onset psoriasis. Our data confirm the previous strong associations with HLA alleles and haplotypes and also reports novel alleles and haplotype association in Pakistani psoriasis patients.

Virtual Reality for Anxiety Reduction in Women Undergoing Colposcopy: A Randomized Controlled Trial.

OBJECTIVE: To test whether headset-delivered virtual reality (VR) content affects satisfaction and/or anxiety in women with cervical squamous intraepithelial lesions undergoing colposcopy and colposcopically guided cervical biopsy. METHODS: In this single-center, randomized trial, the authors measured overall satisfaction (100-mm visual analog scale) and situation-specific anxiety (STAI-S) in 247 women with suspected cervical squamous intraepithelial lesions wearing either no VR headset (arm 1, control) or a VR headset before (arm 2) or before and during colposcopy (arm 3). Secondary endpoints were pain, discomfort, and anxiety during colposcopy, heart rate, and 72-hour follow-up parameters: overall satisfaction, bleeding severity, bleeding duration, pain, and use of analgesics. Analysis was by intention to treat. RESULTS: Median values for overall satisfaction were 100 (interquartile range, 90-100) in controls (n = 83), 100 (95-100) in arm 2 (n = 82), and 100 (95-100) in arm 3 (n = 82), respectively ( p = .92). The median Δ of situational anxiety (baseline vs after colposcopy) was -8 (-13 to -3), -8 (-16.5 to -4), and -10 (-20.5 to -4.5), respectively ( p = .09). The secondary endpoints pain during colposcopy (20 [10-50] vs 20 [10-40] vs 30 [10-50]; p = .65), discomfort during colposcopy (30 [10-50] vs 30 [10-50] vs 20 [10-50]; p = .46), and anxiety during colposcopy (20 [0-50] vs 10 [0-40] vs 10 [0-30]; p = .44), were not different between arms. Follow-up data showed no improvement in the 2 VR arms compared with controls (overall satisfaction, p = .37; bleeding severity, p = .09; pain level, p = .89; duration of pain; p = .23; and use of analgesics; p = .39). Per-protocol analysis did not change the results. CONCLUSIONS: A VR headset showing a 360-degree surround vision film has no effect on satisfaction or anxiety in women undergoing colposcopy.

Effects Of Excessive Screen Time During Online Teaching On The Physical And Mental Health Of Medical And Dental Students.

To assess the effects of excessive screen time on the health of medical and dental students due to online teaching during the COVID-19 pandemic. It was a descriptive cross-sectional study, conducted in Bahria University of Health Sciences from June 2022 to September 2022 after getting ethical approval. A total of 200 students who attended online teaching modules for at least one year through online teaching Apps, were included. A structured questionnaire was distributed using google forms. The results revealed that factors including strain on the eyes, restlessness, declined academic performance and exercise during lockdown, along with feeling connected as a group had a significant association with increased screen time. Excessive screen time has various adverse effects on the physical and mental health of medical and dental students. For improving students' physical and mental health during online teaching we need to change teaching strategies and support the introduction of flipped classroom.

Psychopharmacological impact of ferulic acid on depressive-like behaviors induced by high fat diet in rats models of depression.

Previous studies have been demonstrated that high fat diet can leads to the development of obesity. Obesity is strongly linked with several kinds of neurological and physiological disorders such as type 2 diabetes and cardiovascular diseases. Furthermore studies also suggested that obesity may cause behavioral changes that mainly deal with less locomotor activity and anxiety obesity linked behavioral changes induced by HFD. By using different parameters like growth rate, food intake, levels of anxiety and locomotor activity the finding of this study showed that, that repeated administration of ferulic acid has great profound effect on impairments that were caused by HFD. In our experiments we have observed that those rats which were on HFD and were treated with water only was seemed to be more depressed, less active, and more anxious than those which were administered by ferulic acid doses. From these results we can also suggest that there must be disturbance in the levels of neurotransmitters in an obese individual that caused such kind of changes in the body. This study has implications in the recovery of the changes in the body that were produced by HFD. And ferulic acid can be used as the drug to cure behavioral consequences that were induced by HFD.

Assessment of neuropharmacological consequences induced by dexamethasone administration in rats model of neurodegenerative diseases.

Stress is a well-known and frequently used term among present generation. It has been referred to the response of body to any challenge for a change. It is a natural process and our body is designed to cope with it. However, if stress becomes chronic, it can lead to mental health problems. Stress due to the prolonged administration of glucocorticoid is enabled to produce impressive alterations in rats model shoeing depressive like behavior. In this investigation; purpose was to study the impact of episodic treatment of dexamethasone with respect to behavioral changes in rats. It was hypothesized that repeated administration of dexamethasone could increase stress and thus, psychological stress leading to mood disorders and behavior deficits in rats. Rats were injected daily with DEX (10 mg/ml/kg, orally) and the different behavioral models of the animals were assessed. DEX-treated rats exhibited depressive behavior like greater time to start mobility in a novel environment and elevated anxiety-like behavior in elevated plus maze. However, time spent in light compartment was shorter with repeated administration of DEX. From results it is demonstrated that the administration of DXM for weeks induced stress and consequently, induced a depression-like behaviors in rats models.

Study of HLA class II loci reveals DQB1*03:03:02 as a risk factor for asthma in a Pakistani population.

Asthma, a chronic inflammatory disorder of the lungs and airways, typically results from a combination of multiple environmental and genetic factors. Human leucocyte antigen (HLA) region on chromosome 6p21 encodes the most highly polymorphic loci in the human genome, encoding genes with central roles in the immune function where HLA loci are strongly associated with various immune-mediated diseases such as autoimmunity, allergies and infection. The alleles of HLA class II genes such as DRB1 and DQB1 are the key genetic markers in the development of asthma and have been extensively studied in different ethnicities of the world population. However, the genetic screening of HLA class II alleles and haplotypes in Pakistani asthmatics has not been studied so far. The aim of the present study was to screen the HLA class II DRB1 and DQB1 alleles in asthma cases and controls in a Pakistani population. Seven hundred and two healthy controls and asthma patients were genotyped for HLA class II by sequence-specific polymerase chain reaction assays. The HLA-DRB1 and HLA-DQB1 allele and haplotype frequencies were calculated, and their risk or protective association with asthma was determined. Two-locus haplotypes of DRB1 and DQB1 alleles were imputed using Arlequin version 3.1 software. The signals of association with asthma were stronger at the DQB1 locus as compared to DRB1. HLA DQB1*03:03:02 (odds ratio [OR] = 2.42, 95% confidence interval [CI] = 1.34-4.25) was significantly associated with an increased risk of asthma, as was the haplotype comprised allele DRB1*07:01-DQB1*03:03:02 (OR = 2.40, 95% CI = 1.25-4.62). In contrast, DQB1*06 (OR = 0.39, 95% CI = 0.22-0.70) and DQB1*06:02 (OR = 0.27, 95% CI = 0.10-0.71) emerged as protective alleles for asthma. Our data concludes that the HLA DQB1*03:03:02 allele was a risk allele for asthma, whereas two DQB1 alleles, DQB1*06 and DQB1*06:02, were associated with asthma protection. Our findings highlight a prominent role for HLA-DQB1 alleles in asthma pathogenesis in studied Pakistani cases. More studies, especially with a larger study cohort are needed to confirm the utility of HLA DQB1*03:03:02 as a predictive marker.

Video colposcopy versus headlight for large loop excision of the transformation zone (LLETZ): a randomised trial.

PURPOSE: To compare resected cone mass and resection margin status when performing Large Loop Excision of the Transformation Zone (LLETZ) using video colposcopy (LLETZ-VC) versus a headlight (LLETZ-HL) in women with cervical dysplasia. METHODS: Prospective, randomised trial (monocentric) at a specialised cervical dysplasia unit in a University Hospital. Women with a biopsy-proven CIN2 + or persisting CIN1 or diagnostic LLETZ were recruited and randomised. LLETZ was performed either under video colposcopic vision or using a standard surgical headlight. The primary endpoint was resected cone mass. Secondary endpoints were the rate of involved margins, fragmentation of the specimen, procedure time, time to complete haemostasis (TCH), blood loss, pain, intra- and postoperative complications, and surgeon preference. RESULTS: LLETZ-VC and LLETZ-HL (109 women each) had comparable cone masses (1.57 [0.98-2.37] vs. 1.67 [1.15-2.46] grams; P = 0.454). TCH was significantly shorter in the LLETZ-VC arm (60 [41-95.2] vs. 90 [47.2-130.2] seconds; P = 0.008). There was no statistically significant difference in involved resection margins (6/87 [6.5%] vs. 16/101 [13.7%], P = 0.068) and postoperative complications (13/82 [13.7%] vs. 22/72 [23.4%], P = 0.085). Patient-reported outcomes favoured LLETZ-VC with a lower use of analgesics (6/80 [7.0%] vs. 17/87 [16.3%]; P = 0.049). However, LLETZ-VC was more difficult to perform with significantly lower ratings for handling (7 [5-9] vs. 9 [8-10]; P < 0.001) and general satisfaction (7.5 [5-9] vs. 10 [8-10]; P < 0.001). CONCLUSION: Intraoperative video colposcopy for LLETZ has minimal benefits at the cost of surgeons' satisfaction. CLINICAL TRIAL REGISTRATION: NCT04326049 (ClinicalTrials.gov).

Synthesis, characterization, antioxidant, antileishmanial, anticancer, DNA and theoretical SARS-CoV-2 interaction studies of copper(II) carboxylate complexes.

Copper(II) carboxylate complexes [Cu2(OOCR)4L2] (1) and [Cu2(OOCR`)4OCO(R`)CuL2]n (2), where L = 2-methyl pyridine, R = 2-chlorophenyl acetate and R` = 2-fluorophenyl acetate were synthesized and characterized by FT-IR spectroscopy and single crystal X-ray analysis. Complex 1 exhibits the typical paddlewheel array of a dinuclear copper(II) complex with carboxylate ligands. In complex 2, this scaffold is further extended into a polymeric arrangement based on alternate paddlewheel and square planar moieties with distinct coordination spheres. The complexes showed better 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl radical scavenging activities and have been found to be more potent antileishmanial agents than their corresponding free ligand acid species. UV-Vis absorption titrations revealed good DNA binding abilities {Kb = 9.8 × 104 M-1 (1) and 9.9 × 104 M-1 (2)} implying partial intercalation of the complexes into DNA base pairs along with groove binding. The complexes displayed in vitro cytotoxic activity against malignant glioma U-87 (MG U87) cell lines. Computational docking studies further support complex-DNA binding by intercalation. Molecular docking investigations revealed probable interactions of the complexes with spike protein, the nucleocapsid protein of SARS-CoV-2 and with the angiotensin converting enzyme of human cells.

Design, Synthesis, Crystal Structure, In Vitro and In Silico Evaluation of New N'-Benzylidene-4-tert-butylbenzohydrazide Derivatives as Potent Urease Inhibitors.

BACKGROUND: Hydrazides play a vital role in making biologically active compounds in various fields of chemistry. These determine antioxidant, antidepressant, antimalarial, anti-inflammatory, antiglycating, and antimicrobial activity. In the present study, twenty-three new N' benzylidene-4-(tert-butyl)benzohydrazide derivatives (4-26) were synthesized by the condensation of aromatic aldehydes and commercially available 4-(tert-butyl)benzoic acid. All the target compounds were successfully synthesized from good to excellent yield; all synthesized derivatives were characterized via spectroscopic techniques such as HREI-MS and 1H-NMR. Synthesized compounds were evaluated for in vitro urease inhibition. All synthesized derivatives demonstrated good inhibitory activities in the range of IC50 = 13.33 ± 0.58-251.74 ± 6.82 µM as compared with standard thiourea having IC50 = 21.14 ± 0.425 µM. Two compounds, 6 and 25, were found to be more active than standard. SAR revealed that electron donating groups in phenyl ring have more influence on enzyme inhibition. However, to gain insight into the participation of different substituents in synthesized derivatives on the binding interactions with urease enzyme, in silico (computer simulation) molecular modeling analysis was carried out.

Natural Polymer-Based Graphene Oxide Bio-nanocomposite Hydrogel Beads: Superstructures with Advanced Potentials for Drug Delivery.

The current study sought to create graphene oxide-based superstructures for gastrointestinal drug delivery. Graphene oxide has a large surface area that can be used to load anti-cancer drugs via non-covalent methods such as surface adsorption and hydrogen bonding. To enhance the bio-applicability of graphene oxide, nano-hybrids were synthesized by encapsulating the graphene oxide into calcium alginate hydrogel beads through the dripping-extrusion technique. These newly developed bio-nanocomposite hybrid hydrogel beads were evaluated in structural analysis, swelling study, drug release parameters, haemolytic assay, and antibacterial activity. Doxorubicin served as a model drug. The drug entrapment efficiency was determined by UV-spectroscopy analysis and was found to be high at ⁓89% in graphene oxide hybrid hydrogel beads. These fabricated hydrogel beads ensure the drug release from a hybrid polymeric matrix in a more controlled and sustained pattern avoiding the problems associated with a non-hybrid polymeric system. The drug release study of 12 h shows about 83% release at pH 6.8. In vitro drug release kinetics proved that drug release was a Fickian mechanism. The cytotoxic effect of graphene oxide hybrid alginate beads was also determined by evaluating the morphology of bacterial cells and red blood cells after incubation. Additionally, it was determined that the sequential encapsulation of graphene oxide in alginate hydrogel beads hides its uneven edges and lessens the graphene oxide's negative impacts. Also, the antibacterial study and biocompatibility of fabricated hydrogel beads made them potential candidates for gastrointestinal delivery.

Correlation between Serum Malondialdehyde levels and prevalence of cardiovascular disease in Haemodialysis treated patients.

OBJECTIVE: To investigate the role of serum malondialdehyde as a diagnostic biomarker of free radical production and cardiovascular disease in patients treated with maintenance haemodialysis. METHODS: The case-control study was conducted in the Department of Biochemistry, Basic Medical Sciences Institute (BMSI) of the Jinnah Postgraduate Medical Centre (JPMC), Karachi, and the JPMC Nephrology ward from January 12, 2018, to January 15, 2019, and comprised patients receiving haemodialysis as the cases and healthy controls. Blood samples were obtained from all the subjects for checking the level of serum malondialdehyde. Doppler ultrasonography was employed to detect the intima media thickness ratio of the common carotid artery of all the subjects. Data ws analysed using SPSS 23. RESULTS: Of the 90 subjects, 45(50%) each were cases and controls. There were significant differences in mean values related to age, body mass index and blood pressure between the groups. A statistically significant rise was seen in serum malondialdehyde and carotid artery intima media thickness ratio in the cases compared to the controls (p<0.05). CONCLUSIONS: Serum malondialdehyde was found to be significantly raised in haemodialysis patients compared to the healthy controls.

Inhibition of drug induced Parkinsonism by chronic supplementation of quercetin in haloperidol-treated wistars.

Haloperidol is a neuroleptic medication that is used to treat a wide range of neuropsychiatric conditions. It has been shown to produce medicinal effects against hyperactivity, agitation and mania, as well as schizophrenia. Long-term usage of haloperidol raises the risk of acquiring a neurological condition like Parkinson's disease. Haloperidol causes drug-induced Parkinsonism (DIP) by blocking central dopamine receptors and causing extrapyramidal symptoms during long-term treatment. Quercetin has been shown to reduce the loss of striatal neurons, which may enhance motor capabilities and protect against agents that cause the production of reactive oxygen species (ROS). As a result, present study intended to evaluate the efficacy of quercetin on haloperidol-related motor abnormalities. To develop behavioral impairments, rats (n=24) randomly divided to control and haloperidol group for four weeks. The animals were split into four groups after four weeks: Control, quercetin, haloperidol and haloperidol + quercetin. Animals were administered haloperidol i.p injections of 5mg/kg and quercetin (100mg/kg) orally for 21 days. The treatment of haloperidol-treated rats with quercetin was successful in reversing the haloperidol alterations. It decreased animal food intake and alleviated anxiogenic behavior. The chronic treatment of quercetin further reduced the movement abnormalities in animal model of drug induced pseudo-Parkinson.

Follicular sensitivity index and insulin growth factor-1: Predictor of success after intracytoplasmic sperm injection.

To compare follicular sensitivity index (FSI) and Insulin Growth Factor (IGF) -1 for prediction of oocyte yield, embryo quality and the pregnancy consequence in infertile females booked for Intracytoplasmic Sperm Injection (ICSI). Study design was cross sectional where in 133 infertile females enrolled for ICSI were included. Antral follicle count (AFC), Pre-ovulatory follicle count (PFC), FSI, total dosages of follicle stimulating hormone (FSH); designed as pre-ovulatory follicle count × 100,000/ (antral follicle count × total administered stimulation doses) were estimated. IGF was measured by Enzyme Linked Immuno Sorbent Assay. Efficacious pregnancy conception after Intracytoplasmic Sperm Injection (ICSI) was established by means of intrauterine gestational sac with cardiac activity after transfer of embryo. Odds ratio was determined for clinical pregnancy by means of FSI and IGF-I, p-values <0.05 were considered significant. FSI was found to be a stronger predictor of pregnancy than IGF-I. Both IGF-I and FSI contributed positive association with clinical pregnancy consequences but FSI was found to be a more reliable predictor of clinical pregnancy. The advantage of using FSI over IGF-I is that FSI is a noninvasive test while IGF-I needs blood sampling. We recommend calculation of FSI for prediction of pregnancy outcomes.

Quercetin impact against psychological disturbances induced by fat rich diet.

Obesity is a metabolic disease which promotes by consuming fat rich diet. The consequences may include leptin resistant and initiation of metabolic syndromes. Beside the fact, obesity has psychological impacts it act as a signal of depression by stimulating endogenous stress stimulation. Quercetin is a natural polyphenol, considered as nutraceutical agent which produce antioxidant effects. It is reported to promote energy expenditure and protective mechanism against obesity. This presented work was designed to observe the effects of quercetin on high fat diet treated obese animals with impaired psychological behavior. The study comprised on 36 animals, divided in to different groups as follow: I Normal Diet and II. High fat diet. After the induction of obesity both groups divided in to further three subgroups as control, Quercetin and sertraline. Food intake and body weight along with behavioral analysis for four weeks were done for the assessment of anti-obesity and antidepressant effects of quercetin. The results showed the effective treatment of quercetin in obese animals, it significantly reduced the food intake and body weight of animals. The behavioral test showed the increased locomotor activity in the activity box and improved psychological behavior in quercetin-treated rats in the open field and light-dark box. It is concluded from the present study that quercetin exhibits the ameliorative effects against obesity and associated neuroendocrine alterations.

Fabrication, Evaluation, In Vivo Pharmacokinetic and Toxicological Analysis of pH-Sensitive Eudragit S-100-Coated Hydrogel Beads: a Promising Strategy for Colon Targeting.

The aim of present research aims to fabricate a system of enteric coating of hydrogel beads with pH-sensitive polymer, which shows solubility at pH > 7, and explore their potential to target the colon for drug delivery. Hydrogel beads were fabricated through the extrusion-dripping technique followed by ion gelation crosslinking. Moreover, freeze-thaw cycle was implemented for crosslinking of polyvinyl alcohol (PVA)/Ca-alginate blend beads. The oil-in-oil solvent evaporation method was adopted for the Eudragit coating of hydrogel beads using different coat: core ratios (4:1 or 8:1). Coated and uncoated hydrogel beads were evaluated by in vitro physicochemical properties, swelling and drug release behaviours, and in vivo pharmacokinetics, swelling, and toxicity evaluation. Diclofenac sodium was loaded as an experimental drug. Drug entrapment efficiency for the PVA/Ca-alginate beads was calculated as 98%, and for Ca-alginate beads, it came out to a maximum of 74%. Drug release study at various pH suggested that, unlike uncoated hydrogel beads, the coated beads delay the release of diclofenac sodium in low pH of the gastric and intestinal environment, thus targeting the colon for the drug release. It was concluded that Eudragit S-100-coated hydrogel beads could serve as a more promising and reliable way to target the colon for drug delivery.Graphical abstract.

Drive for muscularity and tendencies of muscle dysmorphia among Pakistani bodybuilders: A prevalence study.

OBJECTIVE: To assess the relationship between drive for muscularity and muscle dysmorphic tendencies in Pakistani bodybuilders. METHODS: The cross-sectional study was conducted in Lahore, Pakistan, from June to September 2017, and comprised male bodybuilders in their early and middle adulthood. Data was collected using an indigenous Drive for Muscularity Inventory and the Body Dysmorphic Disorder factors of the Yale-Brown Obsessive Compulsive Scale. Data was analysed using SPSS 21. RESULTS: There were 211 subjects with a mean age of 26.25±5.946 years. There was a positive relationship between drive for muscularity and tendencies of muscle dysmorphia (p<0.05). Of the total, 130(62%) bodybuilders had a moderate level of drive for muscularity. Unmarried bodybuilders aged 18-25 years had more drive for muscularity compared to married bodybuilders age 26 years and above (p<0.001). CONCLUSIONS: The drive for muscularity and muscle dysmorphic tendencies were found prevalent in Pakistani culture.

How long is too long? Application of acetic acid during colposcopy: a prospective study.

BACKGROUND: Application of acetic acid to the cervix followed by colposcopic assessment with or without colposcopically directed biopsy is the standard test used to detect dysplastic lesions of the cervix. However, there is no evidence-based common standard defining how exactly to perform this test. OBJECTIVE: To prospectively define the optimal timing for the colposcopic assessment of acetowhite lesions. MATERIALS AND METHODS: Consecutive women referred to our colposcopy unit were recruited. Using a standardized colposcopy protocol, we recorded the most severe colposcopic lesion 1, 3, and 5 minutes after application of acetic acid (primary study end point). The time to first appearance of the most severe colposcopic lesion, highest staining intensity, and fading of the most severe colposcopic lesion were video documented (secondary study end points, assessed independently by 3 raters). Results were compared using parametric and nonparametric tests. RESULTS: A total of 300 women were included. After 1 minute, 290 of 300 patients (96.7%) were diagnosed with the most severe colposcopic lesion. This proportion did not improve after 3 minutes (290/300 [96.7%]) or after 5 minutes (233/264 [88.3%]). The proportion of minor and major changes continuously declined over time from 142 in 300 (47.3%; 1 minute) to 107 in 264 (40.5%; 5 minutes) and from 110 in 300 (36.7%) to 91 in 264 (34.5%), respectively. The median time until the first appearance of the most severe colposcopic lesion was 13.5 (interquartile range, 3-27.25) seconds and was significantly lower in high-grade squamous intraepithelial lesion (7 [interquartile range, 1-20] seconds) compared to low-grade squamous intraepithelial lesion (19 [interquartile range, 9-39.5] seconds; P < .001). We observed fading of acetowhite lesions in 78% of cases, occurring at a median of 191 (interquartile range, 120-295) seconds after application of acetic acid. Fading started earlier in high-grade squamous intraepithelial lesion compared to low-grade squamous intraepithelial lesion (179.5 [interquartile range, 110- 253.25] versus 212.5 [interquartile range, 146.5-300]; P = .044). Overall, the net difference between colposcopic assessments at 3 minutes versus at 1 minute was 1 more high-grade squamous intraepithelial lesion and 1 less low-grade squamous intraepithelial lesion. CONCLUSION: It is reasonable to conclude that the best time to identify lesions is 1 minute after the application of acetic acid. Continued evaluation for up to 3 minutes may be considered reasonable for an optimal high-grade squamous intraepithelial lesion yield. However, fading of acetowhite lesions is common, especially in high-grade squamous intraepithelial lesions, and supports a recommendation of not prolonging colposcopy beyond 3 minutes.

Syringe or mask? Loop electrosurgical excision procedure under local or general anesthesia: a randomized trial.

BACKGROUND: Loop electrosurgical excision procedure may be performed under local anesthesia or general anesthesia, and practice patterns differ worldwide. No randomized head-to-head comparison has been published to confirm or refute either practice. OBJECTIVE: This study aimed to compare loop electrosurgical excision procedure under local anesthesia vs general anesthesia regarding patient satisfaction and procedure-related outcomes such as rates of involved margins, complications, pain, and blood loss. STUDY DESIGN: Consecutive women referred to our colposcopy unit were recruited. Loop electrosurgical excision procedure was performed under local anesthesia with 4 intracervical injections of bupivacaine hydrochloride 0.5% or under general anesthesia with fentanyl, propofol, and a laryngeal mask with sevoflurane maintenance. The primary endpoint was patient satisfaction assessed on the day of surgery and 14 days thereafter using a Likert scale (score 0-100) and a questionnaire. Secondary endpoints included rates of involved margins, procedure-related complications, pain, blood loss, and surgeon preference. Results were compared using nonparametric and chi-square tests. RESULTS: Between July 2018 and February 2020, we randomized 208 women, 108 in the local anesthesia arm and 100 in the general anesthesia arm. In the intention-to-treat analysis, patient satisfaction did not differ between the study groups directly after surgery (Likert scale 100 [90-100] vs 100 [90-100]; P=.077) and 14 days thereafter (Likert scale 100 [80-100] vs 100 [90-100]; P=.079). In the per-protocol analysis, women in the local anesthesia arm had significantly smaller cone volumes (1.11 cm3 [0.70-1.83] vs 1.58 cm3 [1.08-2.69], respectively; P<.001), less intraoperative blood loss (Δhemoglobin, 0.2 g/dL [-0.1 to 0.4] vs 0.5 g/dL [0.2-0.9]; P<.001), and higher satisfaction after 14 days (100 [90-100] vs 100 [80-100]; P=.026), whereas surgeon preference favored general anesthesia (90 [79-100] vs 100 [90-100], respectively; P=.001). All other secondary outcomes did not differ between groups (resection margin status R1, 6.6% vs 2.1% [P=.26]; cone fragmentation, 12.1% vs 6.3% [P=.27]; procedure duration, 151.5 seconds [120-219.5] vs 180 seconds [117-241.5] [P=.34]; time to complete hemostasis, 60 seconds [34-97] vs 70 seconds [48.25-122.25] [P=.08]; complication rate, 3.3% vs 1.1% [P=.59]). In a multivariate analysis, parity (P=.03), type of transformation zone (P=.03), and cone volume (P=.02) and not study group assignment, age, body mass index, and degree of dysplasia independently influenced the primary endpoint. CONCLUSION: Loop electrosurgical excision procedure under local anesthesia is equally well tolerated and offers patient-reported and procedure-related benefits over general anesthesia, supporting the preferred practice in some institutions and refuting the preferred practice in others.

Mechanistic Approaches of Internalization, Subcellular Trafficking, and Cytotoxicity of Nanoparticles for Targeting the Small Intestine.

Targeting the small intestine employing nanotechnology has proved to be a more effective way for site-specific drug delivery. The drug targeting to the small intestine can be achieved via nanoparticles for its optimum bioavailability within the systemic circulation. The small intestine is a remarkable candidate for localized drug delivery. The intestine has its unique properties. It has a less harsh environment than the stomach, provides comparatively more retention time, and possesses a greater surface area than other parts of the gastrointestinal tract. This review focuses on elaborating the intestinal barriers and approaches to overcome these barriers for internalizing nanoparticles and adopting different cellular trafficking pathways. We have discussed various factors that contribute to nanocarriers' cellular uptake, including their surface chemistry, surface morphology, and functionalization of nanoparticles. Furthermore, the fate of nanoparticles after their uptake at cellular and subcellular levels is also briefly explained. Finally, we have delineated the strategies that are adopted to determine the cytotoxicity of nanoparticles.