Sex-specific differences in risk factors, comorbidities, diagnostic challenges, optimal management, and prognostic outcomes of heart failure with preserved ejection fraction: A comprehensive literature review.

Due to hormonal variations, heart failure with preserved ejection fraction (HFpEF) remains prevalent in women and affects almost half of the heart failure (HF) patients. Given the yearly death rate of 10-30% and the unavailability of medications targeting HFpEF, the need arises for a better understanding of the fundamental mechanisms of this syndrome. This comprehensive review explores sex-specific differences in traditional risk factors; female-specific factors that may impact HFpEF development and response to therapy, including variations in hormone levels that may occur pre- and post-menopausal or during pregnancy; and disparities in comorbidities, clinical presentation, and diagnostic challenges. Lastly, the review addresses prognostic outcomes, noting that women with HFpEF have a poor quality of life but a higher survival rate. It also discusses novel biomarkers and precision medicine, emphasizing their potential to improve early detection and personalized treatment.

The efficacy of ultrasound-guided upper thoracic erector spinae plane block for postoperative analgesia in proximal shoulder surgery and its effect on phrenic nerve function: A prospective exploratory study.

Background and Aims: The upper thoracic (T2) erector spinae plane block (UT-ESPB) has been proposed as an alternative to interscalene brachial plexus block for postoperative analgesia in shoulder surgery. The current study was conducted to evaluate the same. Material and Methods: Patients scheduled for shoulder surgery under general anesthesia (GA) received ultrasound-guided UT-ESPB. The outcomes measured were diaphragmatic movements, block characteristics, and quality of recovery at 24 h. Results: A total of 43 patients were recruited. The incidence of phrenic nerve palsy was 0%. The sensory level achieved by the maximum number of patients at the end of 30 min was C7-T5 level, and none had a motor block. Forty-two percent of patients did not require rescue analgesia till 24 h postoperative. In the rest of the patients, the mean (SD) duration of analgesia was 724.2 ± 486.80 min, and the mean postoperative requirement of fentanyl was 98.80 ± 47.02 µg. The median pain score (NRS) during rest and movement is 2 to 3 and 3 to 4, respectively. The median quality of recovery score at the end of 24 h after the block was 14 (15-14). Conclusion: The upper thoracic ESPB resulted in a sensory loss from C7-T5 dermatomes without any weakness of the diaphragm and upper limb. However, the block was moderately effective in terms of the total duration of analgesia, postoperative pain scores, analgesic requirement, and quality of recovery in patients undergoing proximal shoulder surgeries under GA. Further studies are required to establish its role due to its poor correlation with sensory spread.

Genome engineering of disease susceptibility genes for enhancing resistance in plants.

Introgression of disease resistance genes (R-genes) to fight against an array of phytopathogens takes several years using conventional breeding approaches. Pathogens develop mechanism(s) to escape plants immune system by evolving new strains/races, thus making them susceptible to disease. Conversely, disruption of host susceptibility factors (or S-genes) provides opportunities for resistance breeding in crops. S-genes are often exploited by phytopathogens to promote their growth and infection. Therefore, identification and targeting of disease susceptibility genes (S-genes) are gaining more attention for the acquisition of resistance in plants. Genome engineering of S-genes results in targeted, transgene-free gene modification through CRISPR-Cas-mediated technology and has been reported in several agriculturally important crops. In this review, we discuss the defense mechanism in plants against phytopathogens, tug of war between R-genes and S-genes, in silico techniques for identification of host-target (S-) genes and pathogen effector molecule(s), CRISPR-Cas-mediated S-gene engineering, its applications, challenges, and future prospects.

DSP: database of disease susceptibility genes in plants.

Host-pathogen interaction is the most crucial factor that evokes the host immune system to fight against pathogens. In contrast to specialized immune cells present in humans and animals, plants have disease resistance (R-) and disease susceptibility (S-) genes. R-genes confer disease resistance and are generally introgressed from wild crop relatives to cultivated crops. S-genes, on the other hand, assist pathogens in establishing contact, displaying counter-defense measures, and spreading the infection. To achieve resistance in a variety of crops, researchers are now focusing on the identification, silencing, editing, or elimination of crucial S-genes. To aid in this field, we created the first curated database of disease susceptibility genes in plants (DSP), with the simple and advanced search tool that allows researchers to restrict the query and mining of specified hits. SSR marker identification and primer designing could be performed with the help of MISA and Primer3 software, respectively. The DSP database is available at http://45.248.163.60/bic/sgenos/ and http://14.139.62.220/sgenos/ .

Comparison between patient state index, bispectral index, and clinical parameters for propofol induction in Indian patients: A prospective study.

Background and Aims: Patient state index (PSI) and bispectral index (BIS) are depth of anesthesia monitors utilized for the dosage of propofol usage for induction. We compare PSI, BIS, and Observer's Assessment of Alertness/Sedation Scale (OAA/S) for propofol dose usage for induction. Material and Methods: Seventy-four ASA I and II patients, aged 18-65 years scheduled for laparoscopic cholecystectomy were included and divided into groups to titrate the drug dosage of propofol needed for induction of anesthesia, monitored by PSI (Group A), BIS (Group B), or clinical OAA/S (Group C). The drug dosage needed for induction was based on a PSI value of 25 ± 2, BIS value of 48 ± 2, and OAA/S value of ≤2 as the endpoint of induction in respective groups. Intraoperative hemodynamic variables and any complications were compared. Results: The mean doses of propofol needed for induction were 2.23 mg/kg (Group A), 2.05 mg/kg (Group B), and 2.11 mg/kg (Group C). A significantly decreased dose was needed to achieve the desired end in Group B compared to Group A (P = 0.01). The hemodynamic variables such as heart rate, systolic blood pressure, and diastolic blood pressure among the three groups were comparable. Conclusion: The clinical method of titrating the dose of propofol for induction and anesthetic depth by the loss of verbal response is comparable to both BIS and PSI monitoring.

GAAP: A GUI-based Genome Assembly and Annotation Package.

Background: Next-generation sequencing (NGS) technologies are being continuously used for high-throughput sequencing data generation that requires easy-to-use GUI-based data analysis software. These kinds of software could be used in-parallel with sequencing for the automatic data analysis. At present, very few software are available for use and most of them are commercial, thus creating a gap between data generation and data analysis. Methods: GAAP is developed on the NodeJS platform that uses HTML, JavaScript as the front-end for communication with users. We have implemented FastQC and trimmomatic tool for quality checking and control. Velvet and Prodigal are integrated for genome assembly and gene prediction. The annotation will be done with the help of remote NCBI Blast and IPR-Scan. In the back- end, we have used PERL and JavaScript for the processing of data. To evaluate the performance of GAAP, we have assembled a viral (SRR11621811), bacterial (SRR17153353) and human genome (SRR16845439). Results: We have used GAAP software to assemble, and annotate a COVID-19 genome on a desktop computer that resulted in a single contig of 27994bp with 99.57% reference genome coverage. This assembly predicted 11 genes, of which 10 were annotated using annotation module of GAAP. We have also assembled a bacterial and human genome 138 and 194281 contigs with N50 value 100399 and 610, respectively. Conclusion: In this study, we have developed freely available, platform-independent genome assembly and annotation (GAAP) software (www.deepaklab.com/gaap). The software itself acts as a complete data analysis package with quality check, quality control, de-novo genome assembly, gene prediction and annotation (Blast, PFAM, GO-Term, pathway and enzyme mapping) modules.

A flexible, interpretable, and accurate approach for imputing the expression of unmeasured genes.

While there are >2 million publicly-available human microarray gene-expression profiles, these profiles were measured using a variety of platforms that each cover a pre-defined, limited set of genes. Therefore, key to reanalyzing and integrating this massive data collection are methods that can computationally reconstitute the complete transcriptome in partially-measured microarray samples by imputing the expression of unmeasured genes. Current state-of-the-art imputation methods are tailored to samples from a specific platform and rely on gene-gene relationships regardless of the biological context of the target sample. We show that sparse regression models that capture sample-sample relationships (termed SampleLASSO), built on-the-fly for each new target sample to be imputed, outperform models based on fixed gene relationships. Extensive evaluation involving three machine learning algorithms (LASSO, k-nearest-neighbors, and deep-neural-networks), two gene subsets (GPL96-570 and LINCS), and multiple imputation tasks (within and across microarray/RNA-seq datasets) establishes that SampleLASSO is the most accurate model. Additionally, we demonstrate the biological interpretability of this method by showing that, for imputing a target sample from a certain tissue, SampleLASSO automatically leverages training samples from the same tissue. Thus, SampleLASSO is a simple, yet powerful and flexible approach for harmonizing large-scale gene-expression data.

Association of Body Mass Index and Waist to Hip Ratio With Gallstone Disease in Patients Visiting Rural Tertiary Care Center in North India.

Introduction. In India the prevalence of gall stone disease varies in different parts of India. Malhotra in 1996 conducted an epidemiological study in Indian Railway employees and showed that North Indians has 7 times higher prevalence of gall stones compared to South Indian employees. It is said that Gall bladder is a disease of "Fatty, Fertile, Females in their Forties". In our daily routine we observe that it is found not only in fatty females but common in average built patients also. Material and Methods. Study includes patients visiting to BPS GMC Khanpur Kalan with diagnosis of gall stone diseases and operated at our center with sample size of 135. Body mass index (BMI) and Waist to Hip ratio are calculated using their standard formulas. All data was compiled in IBM SPSS statistics (20.0). Result. Normal BMI is considered up to 25 and more than 50% patients lie in normal BMI range. Only 13% of cases lie in obese group that is BMI greater than 30. Waist to hip ratio, maximum patients that is BMI greater than 30. Waist to hip ratio, maximum patients that is (83%) lie in group more than 0.85. Minimum Waist to Hip ratio is .77 and maximum Waist to Hip ratio is 1.45. Out of 135 patients 90 patients are having high Waist to Hip ratio. Conclusion. Waist to Hip Ratio (abdominal adiposity) is better indicator of Gall stone diseases than BMI.

Simulated unbound structures for benchmarking of protein docking in the DOCKGROUND resource.

BACKGROUND: Proteins play an important role in biological processes in living organisms. Many protein functions are based on interaction with other proteins. The structural information is important for adequate description of these interactions. Sets of protein structures determined in both bound and unbound states are essential for benchmarking of the docking procedures. However, the number of such proteins in PDB is relatively small. A radical expansion of such sets is possible if the unbound structures are computationally simulated. RESULTS: The DOCKGROUND public resource provides data to improve our understanding of protein-protein interactions and to assist in the development of better tools for structural modeling of protein complexes, such as docking algorithms and scoring functions. A large set of simulated unbound protein structures was generated from the bound structures. The modeling protocol was based on 1 ns Langevin dynamics simulation. The simulated structures were validated on the ensemble of experimentally determined unbound and bound structures. The set is intended for large scale benchmarking of docking algorithms and scoring functions. CONCLUSIONS: A radical expansion of the unbound protein docking benchmark set was achieved by simulating the unbound structures. The simulated unbound structures were selected according to criteria from systematic comparison of experimentally determined bound and unbound structures. The set is publicly available at http://dockground.compbio.ku.edu.

Designing of peptides with desired half-life in intestine-like environment.

BACKGROUND: In past, a number of peptides have been reported to possess highly diverse properties ranging from cell penetrating, tumor homing, anticancer, anti-hypertensive, antiviral to antimicrobials. Owing to their excellent specificity, low-toxicity, rich chemical diversity and availability from natural sources, FDA has successfully approved a number of peptide-based drugs and several are in various stages of drug development. Though peptides are proven good drug candidates, their usage is still hindered mainly because of their high susceptibility towards proteases degradation. We have developed an in silico method to predict the half-life of peptides in intestine-like environment and to design better peptides having optimized physicochemical properties and half-life. RESULTS: In this study, we have used 10mer (HL10) and 16mer (HL16) peptides dataset to develop prediction models for peptide half-life in intestine-like environment. First, SVM based models were developed on HL10 dataset which achieved maximum correlation R/R2 of 0.57/0.32, 0.68/0.46, and 0.69/0.47 using amino acid, dipeptide and tripeptide composition, respectively. Secondly, models developed on HL16 dataset showed maximum R/R2 of 0.91/0.82, 0.90/0.39, and 0.90/0.31 using amino acid, dipeptide and tripeptide composition, respectively. Furthermore, models that were developed on selected features, achieved a correlation (R) of 0.70 and 0.98 on HL10 and HL16 dataset, respectively. Preliminary analysis suggests the role of charged residue and amino acid size in peptide half-life/stability. Based on above models, we have developed a web server named HLP (Half Life Prediction), for predicting and designing peptides with desired half-life. The web server provides three facilities; i) half-life prediction, ii) physicochemical properties calculation and iii) designing mutant peptides. CONCLUSION: In summary, this study describes a web server 'HLP' that has been developed for assisting scientific community for predicting intestinal half-life of peptides and to design mutant peptides with better half-life and physicochemical properties. HLP models were trained using a dataset of peptides whose half-lives have been determined experimentally in crude intestinal proteases preparation. Thus, HLP server will help in designing peptides possessing the potential to be administered via oral route (http://www.imtech.res.in/raghava/hlp/).

Incidence and Risk Factors for Postoperative Visual Loss after Cardiac Surgical Procedures: A Systematic Review.

ABSTRACT: Postoperative visual loss (POVL) is an infrequent yet consequential complication that can follow cardiac surgical interventions. This systematic review aims to provide a comprehensive analysis of the incidence of POVL after cardiac surgery and to delineate the associated risk factors. A comprehensive search was conducted in major medical databases for relevant studies published up to September 2022. Eligible studies reporting on the incidence of POVL and identifying risk factors in patients undergoing cardiac surgery were included. Data extraction was performed independently by two reviewers. The pooled incidence rates and the identified risk factors were synthesized qualitatively. POVL after cardiac surgery has an overall incidence of 0.015%, that is, 15 cases per 100,000 cardiac surgical procedures. Risk factors for POVL include patient characteristics (advanced age, diabetes, hypertension, and preexisting ocular conditions), procedural factors (prolonged surgery duration, cardiopulmonary bypass time, and aortic cross-clamping), anesthetic considerations (hypotension, blood pressure fluctuations, and specific techniques), and postoperative complications (stroke, hypotension, and systemic hypoperfusion). Ischemic optic neuropathy (ION) is an uncommon complication, associated with factors like prolonged cardiopulmonary bypass, low hematocrit levels, excessive body weight gain, specific medications, hypothermia, anemia, raised intraocular pressure, and micro-embolization. Diabetic patients with severe postoperative anemia are at increased risk for anterior ischemic optic neuropathy (AION). Posterior ischemic optic neuropathy (PION) can occur with factors like hypertension, postoperative edema, prolonged mechanical ventilation, micro-embolization, inflammation, hemodilution, and hypothermia.While the overall incidence of POVL postcardiac surgery remains modest, its potential impact is substantial, necessitating meticulous consideration of modifiable risk factors. Notably, prolonged surgical duration, intraoperative hypotension, anemia, and reduced hematocrit levels remain salient contributors. Vigilance is indispensable to promptly detect this infrequent yet visually debilitating phenomenon in the context of postcardiac surgical care.

Comparative Evaluation of Three Different Techniques of Radial Artery Cannulation: A Prospective Randomised Study.

OBJECTIVE: We planned this study to compare three approaches to arterial cannulation, i.e., catheter over the needle, catheter over the guidewire, and ultrasound-guided cannulation, in terms of overall success rate, first pass success rate, time for cannulation and incidence of complications. METHODS: After obtaining informed written consent from the patient, they were randomized into three groups, based on chits in the box technique, to undergo radial artery cannulation as follows: group N (using catheter over needle technique), group W (using catheter over guidewire technique), group U (radial artery cannulations under ultrasound guidance). We calculated a sample size of 50 patients in each group based on the primary endpoint of the overall success rate. The data was analyzed using one-way ANOVA and post hoc Tukey's test. RESULTS: There was a non-statistically significant trend towards a higher overall success rate in groups W and U compared to group N (47 and 46, respectively, compared to 43, p-value 0.35). Similarly, no significant differences were observed concerning any of the characteristics of radial artery cannulation, except the first pass success rate, where the success rate was highest in group W (33, 70.21%), followed by group U (34, 68%) with a p-value of 0.04. CONCLUSION: Though catheter over guidewire and ultrasound-based techniques offer advantages in terms of higher first-pass success rate, they do not significantly increase the overall success rate or reduce the total incidence of complications.

The Comparative Impact of Liberal Versus Conservative Oxygenation in Critically Ill COVID-19 Patients: A Retrospective Study.

Objectives Whether a higher or lower partial pressure of oxygen (PaO2) could impact outcomes in patients with coronavirus disease 2019 (COVID-19) remains a matter of debate. So, we planned this retrospective analysis to determine if a higher or lower partial pressure of oxygen in blood had any effect on outcomes in COVID-19 patients. Material and method The records of COVID-19 patients from the beginning of 2020 to the end of 2022 were scanned. Patients were sub-grouped into two groups based on the partial pressure of oxygen (PaO2) values on arterial blood gas (ABG), i.e., high PaO2 group, PaO2 value of 80-100 mm Hg, and low PaO2 group, PaO2 value of 60-80 mm Hg for the first 48 hours after the initiation of oxygenation and/or mechanical ventilation. The two groups were compared in terms of partial pressure of oxygen in arterial blood to the fraction of inspiratory oxygen (FiO2) concentration (P/F ratio), Sequential Organ Failure Assessment (SOFA) score at presentation and after 48 hours, and clinical outcomes, including mortality, time of mortality, extubation, acute kidney injury (AKI), and change in Glasgow Coma Scale (GCS). Results SOFA score was significantly higher in the low PaO2 group as compared to the high PaO2 group both at baseline (4.59 {1.79} versus 5.51 {1.15}; p-value: 0.005) and at 48 hours (3.06 {1.39} versus 5.11 {2.13}; p-value: 0.007). However, the change in SOFA score over 48 hours did not achieve statistical significance (-1.000 {0.97} versus 0.53 {2.34}; p-value: 0.257). Out of a total of 37 patients, 21 patients died in the high PaO2 group, while 18 patients died in the low PaO2 group. Conclusion Our study highlights that targeting either low or high arterial oxygen content while considering oxygen therapy for COVID-19 patients did not significantly alter the outcomes.

Comparative Efficacy of Intraoperative Patient State Index vs. Bi-Spectral Index in Patients Undergoing Elective Spine Surgery with Neuromonitoring Under General Anaesthesia: A Randomized Controlled Trial.

Objective: Various electroencephalogram-based monitors have been introduced to objectively quantify anaesthesia depth. However, limited data are available on their comparative clinical efficacy in various surgical procedures. Therefore, we planned this study to compare the relative efficacy of patient state index (PSI) vs. Bi-spectral index (BIS) assessment in patients undergoing elective spine surgery under general anaesthesia. Methods: This prospective, parallel-group, single-center study included patients undergoing major spine surgery with neuromonitoring. Patients were randomized into two groups, i.e., group B (undergoing surgery under BIS monitoring) and group P (undergoing surgery under PSI monitoring). The primary objective was to compare the time to eye opening after stopping anaesthetic drug infusions. Results: The mean propofol dose required for induction in group B was 130.45±26.579, whereas that in group P, it was 139.28±17.86 (P value 0.085). The maintenance doses of propofol and fentanyl required for surgery were also comparable between the groups. Time to eye opening was 12.2±4.973 in group B and 12.93±4.19 in group P, with a P value of 0.2664 (U-statistic-684.50). Conclusion: The intraoperative PSI and BIS had similar clinical efficacy in terms of the dose of propofol required for induction, time of induction, maintenance dose of propofol and fentanyl, time of eye opening, and recovery profile in patients undergoing elective spine surgery under neuromonitoring.

Dopamine lesions alter the striatal encoding of single-limb gait.

The striatum serves an important role in motor control, and neurons in this area encode the body's initiation, cessation, and speed of locomotion. However, it remains unclear whether the same neurons also encode the step-by-step rhythmic motor patterns of individual limbs that characterize gait. By combining high-speed video tracking, electrophysiology, and optogenetic tagging, we found that a sizable population of both D1 and D2 receptor expressing medium spiny projection neurons (MSNs) were phase-locked to the gait cycle of individual limbs in mice. Healthy animals showed balanced limb phase-locking between D1 and D2 MSNs, while dopamine depletion led to stronger phase-locking in D2 MSNs. These findings indicate that striatal neurons represent gait on a single-limb and step basis, and suggest that elevated limb phase-locking of D2 MSNs may underlie some of the gait impairments associated with dopamine loss.

A Practical, Systematic Approach to Genetic Diagnosis in a Fetus or Neonate with Congenital Anomalies.

Congenital anomalies contribute significantly to perinatal, neonatal, and infant morbidity and mortality. The causes of these anomalies vary, ranging from teratogen exposure to genetic disorders. A high suspicion for a genetic condition is especially important because a genetic diagnosis carries a risk of recurrence in future pregnancies. Various methods are available for genetic testing, and each plays a role in establishing a genetic diagnosis. This review summarizes a practical, systematic approach to a fetus or neonate with congenital anomalies.

Effectiveness of Simulation-Based Training of Undergraduate Medical Students Regarding the Management of Eclampsia: A Randomized Controlled Educational Trial.

Introduction Obstetric emergencies, like eclampsia, need a quick and accurate response from the treating physician coming into first contact with the patient. Therefore, all doctors, even primary care physicians, interns, and resident doctors, need training to handle such cases proficiently, leaving minimal chances of error. Providing training for the management of these critical conditions on actual patients is not practically feasible. Clinical simulation in obstetrics can be used for the improvement of these skills for undergraduate and postgraduate students. We conducted a non-blinded randomized controlled trial with the primary aim of developing and implementing a module for training undergraduate medical students on the assessment and management of eclampsia and to evaluate and compare it with traditional didactic lectures or case-based learning. Methods The present randomized controlled educational trial was conducted in the Department of Obstetrics and Gynecology, All India Institute of Medical Sciences, Bibinagar, Hyderabad, India. The undergraduate medical students (Phase 3, Part 1) posted in the department during their clinical postings or tutorials were randomized into two groups. A total of 62 students were randomly divided into two groups, Group A and Group B, each consisting of 31 students. However, only 24/31 (77.42%) in Group A and 19/31 (61.3%) in Group B finally agreed to participate in the study. One group (Group A, with 24 participants) was taught the diagnosis and management of antepartum eclampsia through simulation-based training, and the other group (Group B, with 19 participants) was taught the same topic through conventional teaching, which consisted of didactic lectures through PowerPoint presentations and case-based discussion. Learning objectives were kept identical for both groups. Pre- and post-test scores were compared for both groups. Results The mean pre-test score of the simulation group was 6.13 ± 1.39, and that of the conventional teaching group was 6.05 ± 1.54. The post-test score of the simulation group was 9.17 ± 1.34, and that of the conventional teaching group was 7.37 ± 1.70. The simulation group showed an extremely significant (two-tailed p < 0.0001) improvement in their post-test scores when compared to their scores before the module was taught. The difference in the scores of simulated teaching (Group A) and conventional teaching (Group B) was also statistically significant (p = 0.005). Simulation-based learning was found to be more interactive, helpful in providing real-life-like experiences, led to better retention and understanding, and motivated the students for self-directed learning. Conclusion Although both conventional and simulation-based teaching were useful, simulation-based training was more effective in teaching undergraduate medical students regarding the diagnosis and management of eclampsia. Simulation-based learning is more interactive, provides real-life-like experiences, leads to better retention and understanding, and motivates the students for self-directed learning.

Navigating Infertility in Kartagener's Syndrome: A Clinical Case Report.

Kartagener's syndrome is a genetic condition that is caused by a triad of symptoms, which includes bronchiectasis, chronic sinusitis, and situs inversus, and is considered rare. It is caused by defective ciliary motility, leading to impaired mucociliary clearance. We report a case of a 24-year-old male who presented with primary infertility and a long-standing history of recurrent respiratory infections. Physical examination revealed dextrocardia and digital clubbing. Radiological investigations confirmed situs inversus totalis and bronchiectasis. Semen analysis revealed azoospermia. Genetic analysis was not done due to financial constraints. However, the constellation of clinical features was diagnostic of Kartagener's syndrome. The patient was managed with antibiotics and chest physiotherapy. In vitro fertilization (IVF) was advised for infertility. A successful pregnancy was achieved through IVF, indicating viable sperm despite immotility. The aforementioned case underscores the significance of maintaining a heightened sense of suspicion for Kartagener's syndrome in individuals exhibiting unexplained bronchiectasis and infertility. Early diagnosis can prevent chronic respiratory morbidity and enable parenthood through assisted reproduction.

Dopamine lesions alter the striatal encoding of single-limb gait.

The striatum serves an important role in motor control, and neurons in this area encode the body's initiation, cessation, and speed of locomotion. However, it remains unclear whether the same neurons also encode the step-by-step rhythmic motor patterns of individual limbs that characterize gait. By combining high-speed video tracking, electrophysiology, and optogenetic tagging, we found that a sizable population of both D1 and D2 receptor expressing medium spiny projection neurons (MSNs) were phase-locked to the gait cycle of individual limbs in mice. Healthy animals showed balanced limb phase-locking between D1 and D2 MSNs, while dopamine depletion led to stronger phase-locking in D2 MSNs. These findings indicate that striatal neurons represent gait on a single-limb and step basis, and suggest that elevated limb phase-locking of D2 MSNs may underlie some of the gait impairments associated with dopamine loss.

Incidence, risk factors, and outcomes of acute kidney injury in patients undergoing emergency laparotomy - A prospective observational exploratory study.

Background and Aims: Acute kidney injury (AKI) can occur in post-laparotomy patients, with a variable incidence. This study aimed to determine the incidence of AKI in patients undergoing emergency laparotomy under general anaesthesia, the effect of preoperative variables on the development of AKI, and the association of post-operative AKI with patient outcomes. Methods: This prospective exploratory study in patients undergoing emergency laparotomy was followed up for 7 days to determine the incidence of post-operative AKI. We determined the patients developing different severity of AKI based on kidney disease improving global outcome staging. Fisher's exact test or Chi-squared test was used to study the association of demographic variables, and various periopertaive variables on the development of postoperative AKI. The association of AKI with the duration of hospital stay was estimated using the Wilcoxon-Mann-Whitney U Test, and Fisher's exact test was used to study the association between AKI and mortality. Results: No patient had AKI in the pre-operative period. On day 3, 18 patients; on day 5, 28 patients; and on day 7, 24 patients developed AKI. Overall, a maximum of 33 patients (out of 100) developed AKI at any time. Our study found that the American Society of Anesthesiologists (ASA) IV and sepsis were independent risk factors for post-operative AKI. Our results also show a moderate-to-high independent association between AKI and duration of hospital stay and mortality (within 30 days). Conclusion: Incidence of post-operative AKI following emergency laparotomy was 33%. Higher preoperative ASA physical status and sepsis were significantly associated with postoperative AKI development.