Co-delivery of paclitaxel and curcumin loaded solid lipid nanoparticles for improved targeting of lung cancer: In vitro and in vivo investigation.

The objective of this study was to develop nanotechnology-mediated paclitaxel (PAC) and curcumin (CUR) co-loaded solid lipid nanoparticles (PAC-CUR-SLNs) for the treatment of lung cancer, which is a leading cause of death worldwide. Around 85 % cases of lungs cancer constitute non-small cell lung cancer (NSCLC). PAC-CUR-SLNs were prepared via high pressure homogenization. The in vitro drug release of PAC-CUR-SLNs was checked followed by their in vitro cytotoxic investigation using adenocarcinomic human alveolar basal epithelial cells (A549) cell lines. Anticancer effects along with side effects of the synergistic delivery of PAC-CUR-SLNs were studied in vivo, using BALB/c mice. PAC-CUR-SLNs were nano sized (190 nm), homogeneously disseminated particles with %IE of both PAC and CUR above 94 %. PAC-CUR-SLNs released PAC and CUR in a controlled fashion when compared with free drug suspensions. The cytotoxicity of PAC-CUR-SLNs was higher than individual drug-loaded SLNs and pure drugs. Moreover, the co-delivery displayed synergistic effect, indicating potential of PAC-CUR-SLNs in lung cancer treatment. In vivo tumor investigation of PAC-CUR-SLNs exhibited 12-fold reduced tumor volume and almost no change in body weight of BALB/c mice, when compared with the experimental groups including control group. The inhibition of tumor rate on day 28 was 82.7 % in the PAC-CUR-SLNs group, which was significantly higher than the pure drugs and monotherapies. It can be concluded that, encapsulating the co-loaded antitumor drugs like PAC-CUR in SLNs may help in improved targeting of the tumor with enhanced anticancer effect.

Challenges of enbloc mid-sacrectomy as redo surgery for sacral chordoma: a case report.

Enbloc Sacrectomy is the procedure of choice for aggressive sacral lesions but not widely practiced in Pakistan, both by Neurosurgeons and Orthopaedic surgeons. Only one case has been mentioned in indexed local literature so far and that too not operated in Pakistan. The case of a 27 year old neurologically intact male is presented. He had a huge residual mass and midline non-healing wound after two attempts at intralesional debulking and one full course of local irradiation. He presented to the Mayo Hospital, Lahore on 29th December 2021 for a redo surgery of sacral chordoma. A marginal excision was achieved utilizing posterior only approach. This case will help to understand the key steps in enbloc mid-Sacrectomy and importance of involving multidisciplinary team for ensuring adequate wound closure.

Assessing Metal Exposure and Leaching from Discarded Cigarette Butts: Environmental Analysis and Integrated Waste Management Approaches.

Cigarette butts, often discarded as litter, are considered a common form of waste, containing a variety of pollutants within this hazardous residue. This study, which was designed to assess the environmental release of certain metals from cigarette butts, investigates a variety of scenarios under varying climatic conditions. Thus, in order to assess the level of metal contamination, samples of cigarette butts were collected in urban areas from seven popular brands in China, smoked artificially, and examined through graphite furnace atomic absorption (GF-AAS). The findings indicated mean concentrations of 1.77 for Cr, 2.88 for Ni, 12.93 for Cu, 24.25 for Zn, and 1.77 µg/g for Pb in the case of newly smoked butts. The emission of each of the metals increases to 8-10% when cigarette butts remain in the environment for an extended period of time. Furthermore, rainfall can accelerate metal leaching, reaching values of 18-20% compared to the controlled scenario. The worst-case scenario releases 2129.31 kg/year of metals into the environment, while the best-case scenario sees a lower release of 844.97 kg/year. The data reflect variations in metal emissions across different scenarios. There was also a strong correlation between cigarette butts in public spaces and cities. This research highlights the need to educate smokers and increase urban maintenance efficiency to reduce this litter and the metals it leaches into the environment.

Recent advances in nanoformulation-based delivery for cancer immunotherapy.

Cancer is one of the leading causes of mortality worldwide, and its treatment faces several challenges. Phytoconstituents derived from recently discovered medicinal plants through nanotechnology potentially target cancer cells via PI3K/Akt/mTOR pathways and exert their effects selectively through the generation of reactive oxygen species through ß-catenin inhibition, DNA damage, and increasing caspase 3/9 and p53 expression. These nanocarriers act specifically against different cancer cell lines such as HT-29, MOLT-4 human leukemia cancer and MCF-7 cell lines SKOV-3, Caov-3, SW-626, HepG2, A-549, HeLa, and MCF-7. This review comprehensively elaborates on the cellular and molecular mechanisms, and therapeutic prospects of various plant-mediated nanoformulations to attain a revolutionary shift in cancer immunotherapy.

Novel Natural Inhibitors for Glioblastoma by Targeting Epidermal Growth Factor Receptor and Phosphoinositide 3-kinase.

BACKGROUND/AIM: Glioblastoma is an extensively malignant neoplasm of the brain that predominantly impacts the human population. To address the challenge of glioblastoma, herein, we have searched for new drug-like candidates by extensive computational and biochemical investigations. METHOD: Approximately 950 compounds were virtually screened against the two most promising targets of glioblastoma, i.e., epidermal growth factor receptor (EGFR) and phosphoinositide 3-kinase (PI3K). Based on highly negative docking scores, excellent binding capabilities and good pharmacokinetic properties, eight and seven compounds were selected for EGFR and PI3K, respectively. RESULTS: Among those hits, four natural products (SBEH-40, QUER, QTME-12, and HCFR) exerted dual inhibitory effects on EGFR and PI3K in our in-silico analysis; therefore, their capacity to suppress the cell proliferation was assessed in U87 cell line (type of glioma cell line). The compounds SBEH-40, QUER, andQTME-12 exhibited significant anti-proliferative capability with IC50 values of 11.97 ± 0.73 µM, 28.27 ± 1.52 µM, and 22.93 ± 1.63 µM respectively, while HCFR displayed weak inhibitory potency (IC50 = 74.97 ± 2.30 µM). CONCLUSION: This study has identified novel natural products that inhibit the progression of glioblastoma; however, further examinations of these molecules are required in animal and tissue models to better understand their downstream targeting mechanisms.

Ascitic Fluid Lactate Level as a Predictor of Mortality in Cirrhotic Patients Having Spontaneous Bacterial Peritonitis (SBP).

Introduction Limited studies are available for predicting mortality in patients with spontaneous bacterial peritonitis (SBP) based on ascitic fluid analysis. Recently, a proposition has been made regarding the role of ascitic fluid lactate as a better prognostic indicator of mortality in cirrhotic patients with SBP. Therefore, we aimed to evaluate the utility of ascitic fluid lactate in predicting mortality in cirrhotic patients with SBP. Methods This was a prospective, observational study that was conducted in the Hepato-Gastroenterology Department of Sindh Institute of Urology and Transplantation (SIUT), Karachi from 1 January 2022 to 31 December 2022. All the patients having liver cirrhosis with ascites, aged between 18 and 65 years, and presenting with fever and/or abdominal pain were recruited in the study in the first six months (i.e., from 1 January 2022 to 30 June 2022) and were followed for six more months for the outcome. However, those patients on dialysis or those with hepatocellular carcinoma, any other malignancy as per a history of solid organ transplant, a history of HIV infection, or those underlying systemic sepsis or infections other than SBP were excluded from the study. The presence or absence of SBP was confirmed by doing the ascitic fluid analysis. Ascitic fluid lactate levels were also requested in each patient. Mortality was assessed at one, two, three, and six months, respectively. All the data were analyzed using SPSS version 23.0. The area under the receiver operating curve (AUROC) was obtained for ascitic fluid lactate for predicting mortality in SBP. At an optimal cutoff, the diagnostic accuracy of ascitic fluid lactate was obtained. Results The total number of cirrhotic patients included in the study was 123. The majority of the patients belong to Child Turcotte Pugh (CTP) class C (n = 88; 71%). Two third of the patients (65.8%; n = 81) had viral hepatitis i.e., hepatitis B, D, and/or C, as the cause of cirrhosis. Overall mortality was observed in 51(41.5%) patients. Ascitic fluid lactate was significantly raised in patients with SBP than in patients with non-SBP (p = 0.004). The AUROC of ascitic fluid lactate was highest at three months (AUROC = 0.88) followed by six months (AUROC = 0.84), two months (AUROC = 0.804), and one month (AUROC=0.773). At an optimal cut-off of more than or equal to 22.4 mg/dl, ascitic fluid lactate had a sensitivity of 84.9%, specificity of 85.7%, positive predictive value (PPV) of 97.3%, negative predictive value of 42.8% with diagnostic accuracy of 85% in predicting overall mortality in patients with SBP. On sub-analysis, the diagnostic accuracy of ascitic fluid lactate was highest at six months followed by at three, two, and one month, respectively. Conclusion Ascitic fluid lactate showed a good diagnostic utility in predicting the overall mortality in patients with SBP with the best diagnostic accuracy in predicting long-term (six months) mortality. However, further studies are required to validate our results.

Outcome of modified fleur-de-lis latissimus dorsi myocutaneous flap for breast reconstruction.

BACKGROUND: Reconstruction of breast following mastectomy is important in terms of rehabilitating patients of breast cancer. Numerous approaches have been used in the reconstruction process. A procedure that has gained interest of the patients is reconstruction of breast using the autologous form. Main objective of this study is to determine the outcomes of modified fleur-de-lis latissimus dorsi flap in patients undergoing breast reconstruction. METHODOLOGY: This is a retrospective case series which was conducted at the Department of Plastic Surgery, SIMS/Services Hospital, Lahore, from January 2020 till December 2022. 184 patients age 25-60 years and Females with a history of mastectomy, who had to undergo creation of breast shape using a tissue flap from another part of the body at the site of breast following mastectomy were included. All patients were subjected to standard procedure of breast reconstruction with latissimus dorsi flap using modified fleur-de-lis technique and postoperatively weekly assessment in the first month and then monthly until 3 months was carried out and outcome of the study was analysed. RESULTS: The mean age and VAS score of the patients was 49.7 ± 9.17 and 6 ± 2.21, respectively. 57.1 % patients have DCIS, benign in 38 % patients and other tumours were present in 4.9 % patients. Immediate versus delayed reconstruction was done in 63.6 % versus 36.4 % patients respectively. Good aesthetic outcome was achieved in 80.3 % patients CONCLUSION: Modified fleur-de-lis latissimus dorsi flap in patients undergoing breast reconstruction yielded a good aesthetic outcome in the majority of the patients.

Female-specific pancreatic cancer survival from CT imaging of visceral fat implicates glutathione metabolism in solid tumors.

RATIONALE AND OBJECTIVES: To identify if body composition, assessed with preoperative CT-based visceral fat ratio quantification as well as tumor metabolic gene expression, predicts sex-dependent overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: This was a retrospective analysis of preoperative CT in 98 male and 107 female patients with PDAC. Relative visceral fat (rVFA; visceral fat normalized to total fat) was measured automatically using software and corrected manually. Median and optimized rVFA thresholds were determined according to published methods. Kaplan Meier and log-rank tests were used to estimate OS. Multivariate models were developed to identify interactions between sex, rVFA, and OS. Unsupervised gene expression analysis of PDAC tumors from The Cancer Genome Atlas (TCGA) was performed to identify metabolic pathways with similar survival patterns to rVFA. RESULTS: Optimized preoperative rVFA threshold of 38.9% predicted significantly different OS in females with a median OS of 15 months (above threshold) vs 24 months (below threshold; p = 0.004). No significant threshold was identified in males. This female-specific significance was independent of age, stage, and presence of chronic pancreatitis (p = 0.02). Tumor gene expression analysis identified female-specific stratification from a five-gene signature of glutathione S-transferases. This was observed for PDAC as well as clear cell renal carcinoma and glioblastoma. CONCLUSION: CT-based assessments of visceral fat can predict pancreatic cancer OS in females. Glutathione S-transferase expression in tumors predicts female-specific OS in a similar fashion.

Heavy metals mitigation and growth promoting effect of endophytic Agrococcus terreus (MW 979614) in maize plants under zinc and nickel contaminated soil.

Introduction: Heavy metals such as iron, copper, manganese, cobalt, silver, zinc, nickel, and arsenic have accumulated in soils for a long time due to the dumping of industrial waste and sewage. Various techniques have been adapted to overcome metal toxicity in agricultural land but utilizing a biological application using potential microorganisms in heavy metals contaminated soil may be a successful approach to decontaminate heavy metals soil. Therefore, the current study aimed to isolate endophytic bacteria from a medicinal plant (Viburnum grandiflorum) and to investigate the growth-promoting and heavy metal detoxification potential of the isolated endophytic bacteria Agrococus tereus (GenBank accession number MW 979614) under nickel and zinc contamination. Methods: Zinc sulfate and nickel sulfate solutions were prepared at the rate of 100 mg/kg and 50 mg/kg in sterilized distilled water. The experiment was conducted using a completely random design (CRD) with three replicates for each treatment. Results and Discussion: Inoculation of seeds with A. tereus significantly increased the plant growth, nutrient uptake, and defense system. Treatment T4 (inoculated seeds), T5 (inoculated seeds + Zn100 mg/kg), and T6 (inoculated seeds + Ni 100 mg/kg) were effective, but T5 (inoculated seeds + Zn100 mg/kg) was the most pronounced and increased shoot length, root length, leaf width, plant height, fresh weight, moisture content, and proline by 49%, 38%, 89%, 31%, 113%, and 146%, respectively. Moreover the antioxidant enzymes peroxidase and super oxidase dismutase were accelerated by 211 and 68% in contaminated soil when plants were inoculated by A. tereus respectively. Similarly the inoculation of A. tereus also enhanced maize plants' absorption of Cu, Mn, Ni, Na, Cr, Fe, Ca, Mg, and K significantly. Results of the findings concluded that 100 mg/kg of Zn and Ni were toxic to maize growth, but seed inoculation with A. tereus helped the plants significantly in reducing zinc and nickel stress. The A. tereus strain may be employed as a potential strain for the detoxification of heavy metals.

Intravesical mitomycin C efficacy in acidic and alkaline urinary pH: impact on recurrence-free survival rate after TURBT.

Background: Urinary bladder tumor recurrence following transurethral resection of bladder tumor (TURBT) is a common issue. This study aims to determine how urine alkalinization affects bladder tumor recurrence after surgery. Materials and methods: Sixty patients receiving mitomycin C (MMC) therapy after TURBT were divided into two groups based on mean pH values. Twenty-six patients were in group A, whose urine pH was below 5.5. However, there were 34 patients in group B, and their urine pH was higher than 5.5. Both groups of patients were given intravesical MMC once weekly for 6 weeks following TURBT. A cystoscopy was performed as a follow-up at 3, 6, and 12 months. Urine pH and the recurrence-free survival rate were compared using Kaplan-Meier survival analysis and the COX proportional hazard model. Results: The mean time to tumor recurrence in group A (intravesical MMC in acidic urine) and group B (intravesical MMC in alkaline urine) was 12.48 versus 16.84 months, respectively. Alkaline urine pH was identified as an independent predictor of preventing the recurrence of superficial bladder tumors by univariate COX regression analysis. Age, sex, and mean tumor size did not affect the likelihood of tumor recurrence. However, smoking had an association with increased tumor recurrence. Conclusion: Tumor recurrence post-TURBT is delayed in patients with alkaline urine pH. Smoking is an independent risk factor for bladder tumors.

Comparing Efficacy and Safety of Different Doses of Tirzepatide for the Treatment of Type 2 Diabetes Mellitus: A Meta-Analysis of Randomized Controlled Trials.

Our study assessed the efficacy and safety of the three primary tirzepatide (TZP) doses, 5 mg, 10 mg, and 15 mg using network meta-analysis to assess their relative impact on type 2 diabetes mellitus (T2DM) treatment. This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Two authors independently screened online databases, including PubMed, Cochrane Library, and Embase. We employed the keywords "Type 2 diabetes OR T2DM or diabetes" AND "Tirzepatide OR LY3298176 OR twincretin OR dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist" AND "randomized controlled trial". The outcomes evaluated in this study comprised changes in hemoglobin (Hb)A1c levels from baseline (%), changes in weight from baseline (Kg), changes in fasting serum glucose from baseline (mg/dL), and occurrences of serious adverse events (SAE), adverse events (AE) and major adverse cardiovascular events (MACE). A total of eight studies met the inclusion criteria and were included in this meta-analysis. Our findings suggest that among the evaluated doses, TZP at 15 mg demonstrated superior effectiveness in reducing HbA1c, weight, and fasting serum glucose compared to doses of 10 mg and 5 mg. Notably, the reduction in HbA1c and weight showed a dose-dependent trend, with the 15 mg dose achieving the most substantial benefits. The safety analysis indicated that while serious adverse events and major adverse cardiovascular events (MACE) did not significantly differ among the three doses, the risk of overall adverse events was notably higher in the 10 mg and 15 mg TZP groups compared to the 5 mg group.

Predictive ability of physiochemical properties of benzene derivatives using Ve-degree of end vertices-based entropy.

Topological indices relate chemical structure to chemical reactivity, physical properties, and biological activity. Quantitative structure-activity relationships (QSPR) are mathematical models proposed for the correlation of various types of chemical reactivity, biological activity, and physical properties with topological indices/entropies. In this article, we have proposed the QSPR between the ve-degree of end vertices of edge based entropies and the physiochemical properties of benzene derivatives. We have designed a Maple-based algorithm for the computation of entropies. The relationship was analyzed using SPSS. We have shown that the physiochemical properties such as critical pressure, Henry's law, critical temperature, Gibb's energy, logP, critical volume, and molar refractivity can be predicted by entropies. All the results were highly positive and significant. The Randic, Balaban, and redefined third Zagreb entropies showed the best relations with physiochemical properties.Communicated by Ramaswamy H. Sarma.

Dual AAV-based PCDH15 gene therapy achieves sustained rescue of visual function in a mouse model of Usher syndrome 1F.

Mutations in the PCDH15 gene, encoding protocadherin-15, are among the leading causes of Usher syndrome type 1 (USH1F), and account for up to 12% USH1 cases worldwide. A founder truncating variant of PCDH15 has a ∼2% carrier frequency in Ashkenazi Jews accounting for nearly 60% of their USH1 cases. Although cochlear implants can restore hearing perception in USH1 patients, presently there are no effective treatments for the vision loss due to retinitis pigmentosa. We established a founder allele-specific Pcdh15 knockin mouse model as a platform to ascertain therapeutic strategies. Using a dual-vector approach to circumvent the size limitation of adeno-associated virus, we observed robust expression of exogenous PCDH15 in the retinae of Pcdh15KI mice, sustained recovery of electroretinogram amplitudes and key retinoid oxime, substantially improved light-dependent translocation of phototransduction proteins, and enhanced levels of retinal pigment epithelium-derived enzymes. Thus, our data raise hope and pave the way for future gene therapy trials in USH1F subjects.

An Unusual Case of Sublingual Epidermoid Cyst Mimicking Plunging Ranula.

Epidermoid cyst in the oral cavity is uncommon. It is even more rare to see an epidermoid cyst in the sublingual region. We report the case of a 30-year-old male presenting with a swelling in the floor of the mouth extending into the submental and submandibular regions. The midline swelling was painless, soft, and dome-shaped. CT scan contrast revealed the site and extent of swelling. The complete surgical excision of the lesion was performed via a transcervical approach. Histopathology revealed cystic fibrocollagenous tissue covered by squamous epithelium containing some keratin flakes.

Regeneration and modification of cellulose acetate from cigarette waste: Biomedical potential by encapsulation of tetracycline hydrochloride.

Cigarette waste are pervasive litter on Earth, posing a major threat to organisms and ecosystems. However, these waste contain cellulose acetate (CA) and can be recycled, transforming into raw materials for new products. Polymers like CA can be used in biomedical applications as drug carriers and scaffolds for drug release. In this study, cigarette filters waste was collected, recycled and used for fabricating the nanofibrous membrane of cellulose acetate nanofibers (CFCA) through electrospinning technique. Tetracycline hydrochloride (TC) was encapsulated in the nanofibers to prevent bacterial infections. Various analyses were conducted: Scanning Electron Microscope (SEM), Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction Analysis (XRD) and Thermogravimetric analysis (TGA). CA and CFCA exhibited high water uptake properties and exhibited similar breaking stress and strain values. Both CA and CFCA effectively acted as stable drug carriers, with sustained in vitro drug release. Antibacterial activity was demonstrated by the drug-loaded CA and CFCA nanofibers against, Gram-positive bacteria Staphylococcus aureus and Gram-negative bacteria Escherichia coli. Based on their cytotoxicity evaluations on mouse fibroblast cells (L929), CA and CFCA fibrous mats demonstrated no cytotoxicity and similar cell viability results. Consequently, the TC-loaded nanofibers made from CA and CFCA exhibited suitable properties for wound healing applications.

The transcription factor EMB1444-like affects tomato fruit ripening by regulating YELLOW-FRUITED TOMATO 1, a core component of ethylene signaling transduction.

The fleshy fruit of tomato (Solanum lycopersicum) are climacteric and, as such, ethylene plays a pivotal role in their ripening and quality traits. In this study, a basic helix-loop-helix transcription factor, EMB1444-like, was found to induce the expression of YELLOW-FRUITED TOMATO 1 (YFT1), which encodes the SlEIN2 protein, a key element in the ethylene signaling pathway. Yeast one-hybrid and EMSA analyses revealed that EMB1444-like binds to the E-box motif (CACTTG, -1295 bp to -1290 bp upstream of the ATG start codon) of the YFT1 promoter (pYFT1). Suppression of EMB1444-like expression in tomato lines (sledl) using RNAi reduced ethylene production by lowering the expression of 1-AMINOCYCLOPROPANE-1-CARBOXYLATE SYNTHASE 2/4 (ACS2/4) and ACC OXIDASE1 (ACO1) in a positive feedback loop. sledl tomato also showed differences in numerous quality traits related to fruit ripening, compared with the wild type, such as delayed chromoplast differentiation, a decrease in carotenoid accumulation, and delayed fruit ripening in an ethylene-independent manner, or at least upstream of ripening mediated by YFT1/SlEIN2. This study elucidates the regulatory framework of fruit ripening in tomato, providing information that may be used to breed tomato hybrid cultivars with an optimal balance of shelf-life, durability, and high quality.

Smart Nanocarrier-Based Cancer Therapeutics.

Considerable advances in the field of cancer have been made; however, these have not been translated into similar clinical progress which results in the high prevalence and increased cancer-related mortality rate worldwide. Available treatments have several challenges such as off-target side effects, non-specific long-term potential biodisruption, drug resistance, and overall inadequate response rates and high probability of recurrence. The limitations associated with independent cancer diagnosis and therapy can be minimized by an emerging interdisciplinary research field of nanotheranostics which include successful integration of diagnosis and therapy on a single agent using nanoparticles. This may offer a powerful tool in developing innovative strategies to enable "personalized medicine" for diagnosis and treatment of cancer. Nanoparticles have been proven to be powerful imaging tools or potent agents for cancer diagnosis, treatment, and prevention. The nanotheranostic provides minimally invasive in vivo visualization of drug biodistribution and accumulation at the target site with real-time monitoring of therapeutic outcome. This chapter intends to cover several important aspects and the advances in the field of nanoparticles-mediated cancer therapeutics including nanocarrier development, drug/gene delivery, intrinsically active nanoparticles, tumor microenvironment, and nanotoxicity. The chapter represents an overview of challenges associated with cancer treatment, rational for nanotechnology in cancer therapeutics, novel concepts of multifunctional nanomaterials for cancer therapy along with their classification and their clinical prospective in different cancers. A special focus is on the nanotechnology: regulatory perspective for drug development in cancer therapeutics. Obstacles hindering further development of nanomaterials-mediated cancer therapy are also discussed. In general, the objective of this chapter is to improve our perceptive in the design and development of nanotechnology for cancer therapeutics.

Frequency of low birth weight and its relationship with maternal serum zinc: a cross-sectional study.

Fetal and neonatal mortality and morbidity are connected to low birth weight (LBW), which is also associated with slow growth and cognitive development. Several factors, such as maternal nutrition, LBW deliveries, and additional dietary intake, contribute to pregnancy outcomes. This study aimed to compare the maternal serum zinc levels between the LBW and normal birth weight neonates. Moreover, we will also determine the frequency of LBW in the local population. Material and method: This cross-sectional study was conducted at a tertiary care hospital from June 2021 to June 2022. Three hundred eighty-two gravid females with active labor (≥2 uterine contractions in 10 min) were enrolled in the study. Neonates at birth were weighed and divided into two groups: LBW and average or normal birth weight. Maternal serum zinc levels were performed by serum multi-element spectrometry (ICP-DRC-MS method). The data were analyzed using SPSS software. Results: Three hundred eighty-two patients enrolled in this study. The results showed the mean age of patients was 24.04±3.49 years, and the mean maternal zinc levels were found to be 75.32±13.80 µg/dl, respectively. Babies delivered at LBW had low maternal mean serum zinc levels (63.88±10.95 mg/dl) compared to babies with normal birth weight whose levels were comparatively high (83.83±8.57 mg/dl). Conclusion: It can be concluded that maternal dietary factors and nutrition are essential during fetal development and have an important association with birth weight.Zinc supplementation and other minerals should be prioritized because they may increase these infants' birth weight. Increasing maternal zinc consumption has a significant positive linear relationship with infant birth weight.

Sevoflurane inhibited reproductive function in male mice by reducing oxidative phosphorylation through inducing iron deficiency.

Sevoflurane (Sev) is one of the commonly used inhalation anesthetic chemicals in clinics. It has great impact on spermatogenesis and fertilization in male animals. The underlying mechanism remains largely unexplored. Based on our previous research, we hypothesized that Sev induced iron metabolism disturbance in the testis and epididymis and inhibited the spermatogenesis. In this study, two-month-old C57BL/6 male mice were treated with 3% Sev for 6 h, and their fertility (including sperm concentration, sperm mobility, and the number of offspring) was evaluated. Mice testis, epididymis, and sperm were harvested and subjected to Western blot analysis and immunofluorescence analysis. Iron levels were reflected by the gene expression of iron metabolism-related proteins (including ferritin, TfR1, and FpN1) and ICP-MS and Perl's iron staining. Electron transport and oxidative phosphorylation levels were measured by Oxygraph-2k and ATP contents. The activity of ribonucleotide reductase was evaluated by assay kit. DNA synthesis status in testis and/or epididymis was marked with BrdU. Cell proliferation was evaluated by double immunofluorescence staining of specific protein marker expression. Our results revealed that the mice exposed to Sev showed damaged testicular and epididymis structure and significantly reduced the sperm concentration, sperm motility, and fertility. Sev decreases the iron levels through down-regulating the expression of H-ferritin, L-ferritin, and FpN1, and up-regulating the expression of TfR1 in the testis and epididymis. Iron levels also significantly reduced in germ cells which decrease the number of germ cells, including sperm, Sertoli cells, and primary spermatocyte. Iron deficiency not only decreases electron transport, oxidative phosphorylation level, and ATP production but also suppresses the activity of ribonucleotide reductase and the expression of Ki67, DDX4, GATA1, and SCP3, indicating that Sev affects the spermatogenesis and development. Meanwhile, Sev impaired the blood-testis barrier by decreasing the ZO1 expression in the testis and epididymis. The damage effect induced by Sev can be significantly ameliorated by iron supplementation. In conclusion, our study illustrates a new mechanism by which Sev inhibits spermatogenesis and fertility through an oxidative phosphorylation pathway due to iron deficiency of epididymis and testis or sperm. Furthermore, the damaging effects could be ameliorated by iron supplementation.

Evaluating the Safety and Quality of Diagnostic Colonoscopies Performed by General Surgeons: A Retrospective Study.

Introduction Colonoscopy, which is a challenging procedure and requires adequate time to master the skill, is the procedure of choice to visualize colonic mucosa to rule out many colonic pathologies. There is a dearth of published information from real clinical experiences regarding successful procedures and limitations. The end point of colonoscopy is the visualization of the cecal pole by intubating the cecum. Many Europeans and English health organizations recommend that the procedure should have a completion rate of around or above 90%. Gut preparation is an important determinant for a successful procedure and obviates the need for further invasive and/or expensive procedures such as imaging. The majority of colonoscopies are being performed by gastroenterologists (GI) throughout the world, and the role of a surgeon as an endoscopist is in debate. Before this study, neither a retrospective nor a prospective evaluation of the general surgeon's (GS) endoscopy's quality and safety had been evaluated in our institution. Material and method This retrospective observational study was carried out from 1 January 2022 to 31 August 2022 in the Department of Surgery at Mayo Hospital, Lahore, to evaluate colonoscopy completion rates, reason for failure, and complications in terms of bleeding and perforation. All patients undergoing lower gastrointestinal endoscopy (LGiE), both elective and emergency, were included. Patients under 15 years of age and patients known to be hepatitis B-positive or hepatitis C-positive were excluded from the study. All relevant data were entered into a data sheet. Qualitative variables such as gender, cecal intubation, adjusted cecal intubation, gut preparation, reasons for failed colonoscopy, analgesia use, and complications (bleeding and perforation) were calculated as frequency and percentage. Quantitative data such as age and pain score were reported as mean and standard deviation (SD). Details obtained were tabulated and analyzed via the Statistical Package for Social Sciences (SPSS) version 29.0 (IBM SPSS Statistics, Armonk, NY). Results A total of 57 patient data were collected; 35.1% (n=20) were female, and 64.9% (n=37) were males. The cecal intubation rate (CIR) was 49.1% (n=28), and the adjusted rate was 71.9%, excluding incompleteness due to mass obstructing lumen, 8.8% (n=5); planned left colonoscopy, 7% (n=4); sigmoidoscopy, 3.5% (n=2); distal stoma scope, 1.8% (n=1); and colonic stricture, 1.8% (n=1). The prevalent reason for failed colonoscopy was inadequate gut preparation (15.8% {n=9}). Other reasons include patient discomfort, 3.5% (n=2); looping of scope, 7% (n=4); and acute colonic angulation, 1.8% (n=1). No complications were recorded. Conclusion This study shows that colonoscopy can be done by general surgeons safely and effectively with adequate training. High rates of cecal intubation emerge during colonoscopies performed under deep sedation and by skilled colonoscopists. Adequate bowel preparatory regimen is compulsory for quality procedure.