Comprehensive Computational Screening and Analysis of Natural Compounds Reveals Promising Estrogen Receptor Alpha Inhibitors for Breast Cancer Therapy.

Breast cancer remains a leading cause of death among women, with estrogen receptor alpha (ERα) overexpression playing a pivotal role in tumor growth and progression. This study aimed to identify novel ERα inhibitors from a library of 561 natural compounds using computational techniques, including virtual screening, molecular docking, and molecular dynamics simulations. Four promising candidates-Protopine, Sanguinarine, Pseudocoptisine, and Stylopine-were selected based on their high binding affinities and interactions with key ERα residues. Molecular dynamics simulations conducted over 500 nanoseconds revealed that Protopine and Sanguinarine exhibited more excellent stability with minimal fluctuations, suggesting strong and stable binding. In contrast, Pseudocoptisine and Stylopine showed higher flexibility, indicating less stable interactions. Binding free energy calculations further supported the potential of Protopine and Sanguinarine as ERα inhibitors, though their binding strength was slightly lower than that of the reference compound. These findings highlight Protopine and Sanguinarine as leading candidates for further investigation, and in vitro and in vivo studies are recommended to evaluate their therapeutic potential in breast cancer treatment.

Identification of chemoresistance targets in doxorubicin-resistant lung adenocarcinoma cells using LC-MS/MS-based proteomics.

Acquired chemoresistance remains a significant challenge in the clinics as most of the treated cancers eventually emerge as hard-to-treat phenotypes. Therefore, identifying chemoresistance targets is highly warranted to manage the disease better. In this study, we employed a label-free LC-MS/MS-based quantitative proteomics analysis to identify potential targets and signaling pathways underlying acquired chemoresistance in a sub-cell line (A549DR) derived from the parental lung adenocarcinoma cells (A549) treated with gradually increasing doses of doxorubicin (DOX). Our proteomics analysis identified 146 upregulated and 129 downregulated targets in A549DR cells. The KEGG pathway and Gene ontology (GO) analysis of differentially expressed upregulated and downregulated proteins showed that most abundant upregulated pathways were related to metabolic pathways, cellular senescence, cell cycle, and p53 signaling. Meanwhile, the downregulated pathways were related to spliceosome, nucleotide metabolism, DNA replication, nucleotide excision repair, and nuclear-cytoplasmic transport. Further, STRING analysis of upregulated biological processes showed a protein-protein interaction (PPI) between CDK1, AKT2, SRC, STAT1, HDAC1, FDXR, FDX1, NPC1, ALDH2, GPx1, CDK4, and B2M, proteins. The identified proteins in this study might be the potential therapeutic targets for mitigating DOX resistance.

C-reactive protein and procalcitonin: As predictor biomarkers of severity and outcome in children with community-acquired pneumonia.

Our cohort study aimed to compare serum C-reactive protein (CRP) and procalcitonin (PCT) levels in children with community-acquired pneumonia defined by WHO. The former differentiated between pneumonia and severe pneumonia while the latter was better for the outcome of pneumonia.

Comprehensive Review on the Virulence Factors and Therapeutic Strategies with the Aid of Artificial Intelligence against Mucormycosis.

Mucormycosis, a rare but deadly fungal infection, was an epidemic during the COVID-19 pandemic. The rise in cases (COVID-19-associated mucormycosis, CAM) is attributed to excessive steroid and antibiotic use, poor hospital hygiene, and crowded settings. Major contributing factors include diabetes and weakened immune systems. The main manifesting forms of CAM─cutaneous, pulmonary, and the deadliest, rhinocerebral─and disseminated infections elevated mortality rates to 85%. Recent focus lies on small-molecule inhibitors due to their advantages over standard treatments like surgery and liposomal amphotericin B (which carry several long-term adverse effects), offering potential central nervous system penetration, diverse targets, and simpler dosing owing to their small size, rendering the ability to traverse the blood-brain barrier via passive diffusion facilitated by the phospholipid membrane. Adaptation and versatility in mucormycosis are facilitated by a multitude of virulence factors, enabling the pathogen to dynamically respond to various environmental stressors. A comprehensive understanding of these virulence mechanisms is imperative for devising effective therapeutic interventions against this highly opportunistic pathogen that thrives in immunocompromised individuals through its angio-invasive nature. Hence, this Review delineates the principal virulence factors of mucormycosis, the mechanisms it employs to persist in challenging host environments, and the current progress in developing small-molecule inhibitors against them.

Structure of a novel form of phosphopantetheine adenylyltransferase from Klebsiella pneumoniae at 2.59 Å resolution.

Phosphopantetheine adenylyltransferase (EC. 2.7.7.3, PPAT) catalyzes the penultimate step of the multistep reaction in the coenzyme A (CoA) biosynthesis pathway. In this step, an adenylyl group from adenosine triphosphate (ATP) is transferred to 4'-phosphopantetheine (PNS) yielding 3'-dephospho-coenzyme A (dpCoA) and pyrophosphate (PPi). PPAT from strain C3 of Klebsiella pneumoniae (KpPPAT) was cloned, expressed and purified. It was crystallized using 0.1 M HEPES buffer and PEG10000 at pH 7.5. The crystals belonged to tetragonal space group P41212 with cell dimensions of a = b = 72.82 Å and c = 200.37 Å. The structure was determined using the molecular replacement method and refined to values of 0.208 and 0.255 for Rcryst and Rfree factors, respectively. The structure determination showed the presence of three crystallographically independent molecules A, B and C in the asymmetric unit. The molecules A and B are observed in the form of a dimer in the asymmetric unit while molecule C belongs to the second dimer whose partner is related by crystallographic twofold symmetry. The polypeptide chain of KpPPAT folds into a ß/α structure. The conformations of the side chains of several residues in the substrate binding site in KpPPAT are significantly different from those reported in other PPATs. As a result, the modes of binding of substrates, phosphopantetheine (PNS) and adenosine triphosphate (ATP) differ considerably. The binding studies using fluorescence spectroscopy indicated a KD value of 3.45 × 10-4 M for ATP which is significantly lower than the corresponding values reported for PPAT from other species.

Impact of weight reduction on structural and functional parameters of the optic nerve in idiopathic intracranial hypertension.

PURPOSE: To evaluate the effect of weight reduction on the structural and functional parameters of the optic nerve in established cases of papilledema in Idiopathic Intracranial Hypertension (IIH). METHODS: A prospective observational study in early and established cases of papilledema in IIH presenting from December 2019 to February 2021. Functional parameters (visual acuity, contrast sensitivity, mean deviation, VER), structural parameters (RNFL, GCL-IPL, and optic disc height), and clinical grading of papilledema were measured at baseline and every 6 weeks for 6 months. All patients underwent medical (oral acetazolamide) and diet therapy. RESULTS: Mean body mass index (BMI) at presentation was 26.32 ± 3.52 kg/m² and the mean change in BMI over 6 months was 1.27 ± 0.50 kg/m². 67% of eyes had papilledema of grades 2-3 at the presentation. At the end of 6 months, 75% of eyes had grade 1 papilledema while 13% showed complete resolution. A reduction of 5.32 ± 3.58 in mean deviation (r = 0.316; p-value 0.01) and gain in VER P100 amplitude of 4.2 ± 2.7 µV (r = 0.40; p-value 0.003) were noted over 6 months with reduction in BMI over 6 months. A statistically significant reduction in optic disc height (ODH) was noticed with BMI reduction over 6 months (p = 0.0007; r = 0.45).A reduction of 1.72 ± 0.90 kg/m² (equivalent to 6.53% weight loss) in BMI was associated with a four-grade change in clinical grading of papilledema. CONCLUSION: Reduction in BMI had a significant impact on both structural and functional parameters of the optic nerve in IIH. The involvement of a well-certified dietician should be an integral part of treatment in IIH.

Impact of subgingival instrumentation on systemic inflammation and serum bone resorption marker in premenopausal women with periodontitis: a prospective interventional study.

OBJECTIVES: Inflammatory disorders including periodontitis have been investigated for their impact on systemic inflammation and bone health. The present study was conducted with an aim to evaluate impact of control of periodontal inflammation through subgingival instrumentation on serum interleukin 6 and serum C-terminal telopeptide of type I collagen (CTX) in premenopausal females with stage II and III periodontitis. METHOD AND MATERIALS: In this single-arm prospective study, periodontal parameters, serum interleukin 6, serum CTX, and hematologic parameters (total leukocyte count, differential leukocyte count, platelet count, mean platelet volume, and platelet distribution width) were assessed at baseline. Subgingival instrumentation was done, and oral hygiene instructions were given. At week 4, professional plaque control was performed, and oral hygiene instructions were reinforced. Serum and hematologic parameters were reassessed at 8 weeks after subgingival instrumentation, in individuals meeting the clinical endpoints (ie, bleeding on probing < 10%). RESULTS: There was significant reduction in serum interleukin 6 of 0.168 ± 0.164 pg/mL (P = .000), and serum CTX of 17.459 ± 4.363 pg/mL (P = .000) at 8 weeks after subgingival instrumentation. There was significant decrease in eosinophil count (P = .018) and mean platelet volume (P = .016) at 8 weeks after subgingival instrumentation; however, no significant change was found in other hematologic parameters. CONCLUSION: Following subgingival instrumentation, biomarkers of both systemic inflammation (interleukin 6) and bone turnover (CTX) were observed to reduce significantly. This finding hints towards a positive impact of periodontal intervention on bone health.

The Impacts and Changes Related to the Cancer Drug Resistance Mechanism.

BACKGROUND: Cancer drug resistance remains a difficult barrier to effective treatment, necessitating a thorough understanding of its multi-layered mechanism. OBJECTIVE: This study aims to comprehensively explore the diverse mechanisms of cancer drug resistance, assess the evolution of resistance detection methods, and identify strategies for overcoming this challenge. The evolution of resistance detection methods and identification strategies for overcoming the challenge. METHODS: A comprehensive literature review was conducted to analyze intrinsic and acquired drug resistance mechanisms, including altered drug efflux, reduced uptake, inactivation, target mutations, signaling pathway changes, apoptotic defects, and cellular plasticity. The evolution of mutation detection techniques, encompassing clinical predictions, experimental approaches, and computational methods, was investigated. Strategies to enhance drug efficacy, modify pharmacokinetics, optimizoptimizee binding modes, and explore alternate protein folding states were examined. RESULTS: The study comprehensively overviews the intricate mechanisms contributing to cancer drug resistance. It outlines the progression of mutation detection methods and underscores the importance of interdisciplinary approaches. Strategies to overcome drug resistance challenges, such as modulating ATP-binding cassette transporters and developing multidrug resistance inhibitors, are discussed. The study underscores the critical need for continued research to enhance cancer treatment efficacy. CONCLUSION: This study provides valuable insights into the complexity of cancer drug resistance mechanisms, highlights evolving detection methods, and offers potential strategies to enhance treatment outcomes.

Evaluation of change in objective cyclotorsion after various inferior oblique-weakening procedures.

PURPOSE: To study the effect of four types of inferior oblique-weakening procedures on ocular torsion: inferior oblique recession (IOR), recession and antero-positioning (RAP), anterior transposition as practiced by Elliot and Nankin (EN), and anterior and nasal transposition (ANT). METHODS: The medical records of 72 consecutive patients >10 years of age undergoing inferior oblique weakening for primary or secondary inferior oblique overaction (IOOA) with or without horizontal rectus surgery were reviewed retrospectively. The 106 included eyes were assigned to one of the four groups according to the type of inferior oblique-weakening procedure. The severity of IOOA and the amount of V pattern guided the choice of procedure. IOOA, disk-fovea angle (DFA), and the amount of V pattern were recorded preoperatively. Measurements were repeated postoperatively at 1 week, 4 weeks, and 3 months. Change in the DFA was used to study the change in objective cyclotorsion in all four groups. RESULTS: A significant incyclotorsional shift was seen in all four groups at postoperative 3 months. The mean reduction in excyclotorsion 3 months postoperatively was 3.65° ± 4.84° for IOR, 5.31° ± 4.64° for RAP, 6.10° ± 3.89° for EN, and 16.62° ± 8.72° ANT; it was significantly higher in the ANT group compared with the other three groups. Reduction in DFA was also correlated with preoperative DFA overall, and for all procedures except IOR (P ≤ 0.005). CONCLUSIONS: All four inferior oblique-weakening procedures reduced excyclotorsion; the largest reductions in our study were seen in cases treated using ANT of the inferior oblique.

Defective quality control autophagy in Hyperhomocysteinemia promotes ER stress and consequent neuronal apoptosis through proteotoxicity.

Homocysteine (Hcy), produced physiologically in all cells, is an intermediate metabolite of methionine and cysteine metabolism. Hyperhomocysteinemia (HHcy) resulting from an in-born error of metabolism that leads to accumulation of high levels of Hcy, is associated with vascular damage, neurodegeneration and cognitive decline. Using a HHcy model in neuronal cells, primary cortical neurons and transgenic zebrafish, we demonstrate diminished autophagy and Hcy-induced neurotoxicity associated with mitochondrial dysfunction, fragmentation and apoptosis. We find this mitochondrial dysfunction is due to Hcy-induced proteotoxicity leading to ER stress. We show this sustained proteotoxicity originates from the perturbation of upstream autophagic pathways through an aberrant activation of mTOR and that protetoxic stress act as a feedforward cues to aggravate a sustained ER stress that culminate to mitochondrial apoptosis in HHcy model systems. Using chemical chaperones to mitigate sustained ER stress, Hcy-induced proteotoxicity and consequent neurotoxicity were rescued. We also rescue neuronal lethality by activation of autophagy and thereby reducing proteotoxicity and ER stress. Our findings pave the way to devise new strategies for the treatment of neural and cognitive pathologies reported in HHcy, by either activation of upstream autophagy or by suppression of downstream ER stress. Video Abstract.

Good outcome of surgical treatment for contaminated penile wound due to a fall from stairs: a case report.

Background: Penile trauma due to the associated stigma poses a diagnostic challenge. The causes of isolated penile injuries include zipper injuries (mainly in children), falls, burns, during fellatio, self-mutilation (Klingsor syndrome), and rarely purposeful forceful bending of the erect penis (Taqaandan). Delayed management of penile trauma might increase the risk of infection, rarely leading to sepsis acutely or structural and functional disabilities in the long run. We believe our report is the first to contribute data on a patient with a delayed presentation of contaminated penile wound who recovered well with prompt management. Case Description: A traumatic laceration of the penis due to a fall from stairs is extremely unexpected. Here we present the case of a 14-year-old boy who slipped from the stairs and got an isolated American Association for the Surgery of Trauma (AAST) Grade-1 ventrolateral penile skin laceration. He took home remedies for 10 days before reporting with a contaminated wound. The patient was first managed conservatively with antibiotics [Amoxyclav 625 mg thrice daily (TDS) and Metronidazole 400 mg TDS], wound care, and then treated surgically, helping wound repair. He recovered well after the treatment and retained normal urinary and sexual function. Conclusions: Penile trauma is severely under-reported due to the stigma associated with it. Early diagnosis and prompt management are imperative to limit complications. A detailed history helps to evaluate the exact cause and check out possibilities of sexual assault. Appropriate management in tandem with patient education and an attempt to de-stigmatize the interaction helps favorable long-term outcomes.

Chloroquine synergizes doxorubicin efficacy in cervical cancer cells through flux impairment and down regulation of proteins involved in the fusion of autophagosomes to lysosomes.

Drug repurposing holds abundant opportunity in the development of novel anticancer drugs. Chloroquine (CQ), a FDA approved anti-malarial drug, is demonstrated to enhance anticancer efficacy of standard anticancer drugs including doxorubicin (DOX) in several types of cancer cells. Here, we aimed to exploit the chemosensitizing effects of CQ against DOX in human cervical cancer (HeLa) cells that remains to be investigated yet. We show that a combination of DOX (40 nM) and CQ (40 µM) resulted in a synergistic cytotoxicity (combination index; CI < 1) in HeLa cells compared to the DOX or CQ alone. Synergistic effect of the combination (DOX + CQ) was associated with the impaired autophagic flux and enhanced apoptosis. Following treatment with the combination (DOX + CQ), the level of p62/SQSTM and LC-3II proteins was increased, while a decrease was noted in the expression of LAMP-2, Syntaxin17, Rab 5, and Rab 7 proteins that play critical roles in the fusion of autophagosomes to lysosomes. Autophagy inhibition by combination (DOX + CQ) enhanced the apoptotic cell death synergistically by increasing the cleavage of procaspase-3 and PARP1. Further, a prior incubation of HeLa cells with Z-VAD-FMK (a pan-caspase inhibitor) for 4 h, suppressed the combination (DOX + CQ)-induced cell death. Our data suggest that a combination of DOX + CQ had a better anti-cancer efficacy in HeLa cells than either of the drugs alone. Thus, CQ, as a repurposed drug, may hold the potential to synergize anticancer effects of DOX in cervical cancer cells.

Crosstalk between epigenetics and tumor promoting androgen signaling in prostate cancer.

Prostate cancer (PCa) is one of the major health burdens among all cancer types in men globally. Early diagnosis and efficacious treatment options are highly warranted as far as the incidence of PCa is concerned. Androgen-dependent transcriptional activation of androgen receptor (AR) is central to the prostate tumorigenesis and therefore hormonal ablation therapy remains the first line of treatment for PCa in the clinics. However, the molecular signaling engaged in AR-dependent PCa initiation and progression is infrequent and diverse. Moreover, apart from the genomic changes, non-genomic changes such as epigenetic modifications have also been suggested as critical regulator of PCa development. Among the non-genomic mechanisms, various epigenetic changes such as histones modifications, chromatin methylation and noncoding RNAs regulations etc. play decisive role in the prostate tumorigenesis. Given that epigenetic modifications are reversible using pharmacological modifiers, various promising therapeutic approaches have been designed for the better management of PCa. In this chapter, we discuss the epigenetic control of tumor promoting AR signaling that underlies the mechanism of prostate tumorigenesis and progression. In addition, we have discussed the approaches and opportunities to develop novel epigenetic modifications based therapeutic strategies for targeting PCa including castrate resistant prostate cancer (CRPC).

Ethical issues with MS (Ayurved) Shalya Tantra/Shalakya Tantra: Need for public debate.

In November 2020, the Central government amended the Central Council of Indian Medicine Regulations, 2016, to introduce formal training in Shalya (general surgery) and Shalakya (diseases of ear, nose, throat, ENT, eye, head, oro-dentistry) specialisations for postgraduate students of Ayurveda [1].

An Assessment of the Etiologies Associated With Acute Abdomen Subjected to Exploratory Laparotomy: A Study From a Rural Area of Himachal Pradesh.

Background The aim of this retrospective study is to establish a correlation between clinical features, surgical diagnosis, and the final diagnosis of laparotomies, as well as to establish the relationship between preoperative delay on the outcomes of surgery in the form of mortality and morbidity. Emergency surgery is high-risk in patients with acute abdomen with uncertain diagnosis. The results of surgery are remarkable and provide quick relief to the suffering and agony of patients with the dreadful condition of acute generalized peritonitis. Methodology Patients presenting with complaints of acute abdomen who needed laparotomy based on clinical judgment and investigations were included in this study. The study data were reviewed from April 2007 to January 2011 and March 2014 to February 2016 in a government hospital. Results A total of 174 patients with acute abdomen in whom there was an indication of laparotomy based on clinical judgment and radiological investigations were selected. Most patients had gastrointestinal perforation (n = 115) and acute intestinal obstruction (n = 23). The most important clinical features analyzed were abdominal tenderness (n = 160), guarding (n = 153), distention (n = 75), and tachycardia (n = 63). Conclusions Among the total patients, 150 underwent surgery within 24 hours of the presentation in the emergency and the remaining after 24 hours. The most common cause of laparotomy was a duodenal perforation in 79 patients and gastric perforation in 24 patients. A total of 114 patients developed no complications postoperatively. Among patients who developed postoperative complications, wound sepsis and acute respiratory distress syndrome were the most common. Mortality was noted in three patients.

A Case Report of Rare Synchronous Esophageal Malignancies With Dissimilar Histology: Squamous Cell Carcinoma and Small Cell Carcinoma.

The presence of synchronous primary malignancies is a rare phenomenon reported in the literature. Most synchronous malignancies reported include carcinomas and adenocarcinomas of the gastrointestinal tract, head and neck cancers, thyroid and breast cancers. Among the neuroendocrine tumors, carcinoid tumors in the duodenum or the esophagus are most commonly reported with other primary malignancies. We report the case of a 56-year-old male with tobacco use disorder, presenting with dysphagia and weight loss for six months, who was thought to have multicentric squamous cell carcinoma of the esophagus. In actuality, he was diagnosed with synchronous metastatic neuroendocrine tumor (NET) favoring small cell carcinoma and squamous cell carcinoma of the esophagus. The patient responded well to minimally invasive thoracoscopic esophagectomy with regional lymphadenectomy followed by chemotherapy and radiation therapy. We have not been able to find a literature referencing the presence of synchronous small cell carcinoma and squamous cell carcinoma of the esophagus, making our case unique.

Ventral Hernia Repair Using Ventralex® ST Patch: A Single-Center Study of Clinical Outcomes and Complications.

Background Ventralex® ST (Bard Davol Inc, Warwick, RI) patch is a composite self-expanding and non-absorbable mesh used to reinforce ventral hernia repair. This study was conducted to assess the efficacy, post-operative clinical outcomes, the duration of operation, and complications deciding the post-operative duration/need of hospitalization in patients of small ventral hernia after their open surgical repair using Ventralex ST hernia patch. Materials and methods We included 36 patients diagnosed with a small (<2 cm defect size) ventral hernia who underwent open mesh repair following strict surgical methodology using Ventralex® ST hernia patch between September 2018 and April 2020. It was a prospective observational study. Clinically relevant characteristics, along with operative and post-operative data collected through direct interview, clinical examination, and a pretested proforma, were analyzed prospectively. Results Thirty-four patients (94.5%) were observed to have an operative time of fewer than 60 minutes, with an average duration of 30-40 minutes. Thirty-one patients (86%) were discharged within 48 hours of surgery, out of which 17 patients (47.2%) were discharged within 24 hours of surgery and 14 patients (38.8%) within 48 hours. Only five patients (13.88%) had a prolonged hospital stay for more than 48 hours due to post-operative complications. Three patients (8.33%) acquired post-surgical wound infection, whereas two (5.55%) developed seroma. Nevertheless, just one patient (2.7%) reportedly developed both infection and seroma after surgery. No cases of mesh infection or recurrences were noted. Conclusion This study demonstrates that open repair of small (<2 cm defect size) ventral hernia using the Ventralex® ST hernia patch can be an extremely safe and effective method. Furthermore, it has excellent clinical outcomes when meticulously used with an easily reproducible surgical technique, which requires less intra-operative time, has minimal post-operative complications and negligible recurrence rate, along with reduced post-op hospital stay (86% of patients being discharged within 48 hours).

The Assessment of Immediate Postoperative Delirium in Neurologically Intact Adult Patients Admitted to the Post-anesthesia Care Unit: A Cross-Sectional Study.

Background Immediate postoperative delirium (IPD) in the post-anesthesia care unit (PACU) can cause significant morbidity affecting everyday activities and length of stay with cost implications. This study was undertaken to find the proportion of IPD in PACU and its association with anesthesia and other perioperative factors. Methods After obtaining ethical approval and informed consent, this cross-sectional study was conducted in the PACU. A total of 600 consecutive adult patients (American Society of Anesthesiologists (ASA) 1-3) posted for surgery were approached between January and March 2019, of which 402 patients without neurological diseases and language and hearing discrepancies were studied. All patients had the intervention of surgery under anesthesia in a usual manner. Delirium was assessed preoperatively, postoperatively at 15 and 30 minutes, and before discharge from the PACU. IPD was assessed using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) score, while sedation/agitation was assessed using the Richmond Agitation-Sedation Scale (RASS). The primary outcomes were the proportion of IPD, association with anesthesia, and perioperative risk factors. The secondary outcomes were the length of stay, delirium treatment, and mortality. Results Overall, the IPD proportion was 14.7%. A significant association was demonstrated with premedication with midazolam (odds ration (OR): 3.2; 95% confidence interval (CI): 1.42-7.35; P=0.003), general anesthesia (GA) (OR: 6.3; 95% CI: 2.23-17.8; P<0.001), duration of anesthesia (126 versus 95 minutes; P=0.001), laparoscopic mode of surgical access (OR: 3.4; 95% CI: 1.8-6.4; P<0.001), and postoperative RASS >/< 0 (OR: 10.6; 95% CI: 4.69-24.11; P<0.001) at 30 minutes and before discharge from the PACU. Multivariate analysis showed the strongest association of RASS at 30 minutes with IPD. Conclusion The proportion of IPD was found to be 14.7% in this study, and the chances of developing IPD are high if the patient is not awake and calm in the PACU, especially if midazolam is administered as premedication, followed by general anesthesia (GA) for a long duration.

Post-laparotomy Hypoxia: A Case Series.

Postoperative hypoxia is a challenge for surgeons. With the advent of better anesthesia and minimal access surgical techniques, the incidence of postoperative hypoxia in elective cases has decreased. However, the incidence in life-saving emergency procedures still poses a possible threat, and cases seem under-reported. We report a series of five cases of postoperative hypoxia after laparotomy. These cases comprise mesenteric laceration, proximal jejunal perforation, perforated duodenal ulcer, abdominal tuberculosis, and fall from height. Despite different etiologies, they landed up with the complication of postoperative hypoxia, which was attributable to the type of procedure they underwent and not the indication of the procedure itself. Thus, they form an interesting collection of post-laparotomy hypoxia cases. We present them with a compilation of probable causes of postoperative hypoxia in such cases. Postoperative hypoxia presents a diagnostic challenge and requires timely suspicion, prompt intervention to eliminate the cause, and good postoperative care. The major causes include incomplete lung re-expansion, pain-induced restriction in chest-wall/diaphragm mobility, prolonged surgery, a complication of pre-existing lung disease, residual effects of some drugs, and iatrogenic causes. We, therefore, recommend the use of postoperative oxygen support and diligent monitoring of vitals in all cases of laparotomy, allowing prompt and timely patient management. Future studies are warranted to explore the prevalence and possible causes of post-laparotomy hypoxia.

The Mechanism of Action of Lactoferrin - Nucleoside Diphosphate Kinase Complex in Combating Biofilm Formation.

BACKGROUND: The ESKAPE group of pathogens which comprise of multidrug resistant bacteria, namely Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species are the cause of deadly nosocomial infections all over the world. While these pathogens have developed robust strategies to resist most antibiotics, their ability to form biofilms is one of their most combative properties. Hence there is an urgent need to discover new antibacterial agents which could prevent or destroy the biofilms made by these bacteria. Though it has been established that lactoferrin (LF), a potent iron binding antibacterial, antifungal, and antiviral protein displays anti-biofilm properties, its mechanisms of action, in addition to its iron chelation property, still remains unclear. OBJECTIVE: The binding and inhibition studies of LF with the enzyme Nucleoside diphosphate Kinase (NDK) and its elastase cleaved truncated 12 kDa fragment (12-NDK). METHODS: The characterization studies of NDK and 12-NDK using florescence spectroscopy, dynamic light scattering, size exclusion chromatography and ADP-glo Kinase Assay. Inhibition studies of LF-NDK using ADP-glo kinase assay, Surface Plasmon Resonance and Biofilm inhibition studies. RESULTS: NDK and 12-NDK were cloned, expressed and purified from Acinetobacter baumannii and Pseudomonas aeruginosa. The characterization studies revealed NDK and 12-NDK from both species are stable and functional. The inhibition studies of LF-NDK revealed stable binding and inhibition of kinase activity by LF. CONCLUSION: The binding and inhibition studies have shown that while LF binds with both the NDK and their truncated forms, it tends to have a higher binding affinity with the truncated 12 kDa fragments, resulting in their decreased kinase activity. This study essentially gives a new direction to the field of inhibition of biofilm formation, as it proves that LF has a novel mechanism of action in other than iron sequestration.