Acute kidney injury in patients with cirrhosis: Acute Disease Quality Initiative (ADQI) and International Club of Ascites (ICA) joint multidisciplinary consensus meeting.

Patients with cirrhosis are prone to developing acute kidney injury (AKI), a complication associated with a markedly increased in-hospital morbidity and mortality, along with a risk of progression to chronic kidney disease. Whereas patients with cirrhosis are at increased risk of developing any phenotype of AKI, hepatorenal syndrome (HRS), a specific form of AKI (HRS-AKI) in patients with advanced cirrhosis and ascites, carries an especially high mortality risk. Early recognition of HRS-AKI is crucial since administration of splanchnic vasoconstrictors may reverse the AKI and serve as a bridge to liver transplantation, the only curative option. In 2023, a joint meeting of the International Club of Ascites (ICA) and the Acute Disease Quality Initiative (ADQI) was convened to develop new diagnostic criteria for HRS-AKI, to provide graded recommendations for the work-up, management and post-discharge follow-up of patients with cirrhosis and AKI, and to highlight priorities for further research.

Terpenoids in Diabetic Nephropathy: Advances and Therapeutic Opportunities.

Diabetic nephropathy (DN) is the foremost ailment resulting in end-stage renal damage. Chronic hyperglycaemia and hyperlipidaemia are the foremost reason for disease progression. The disease is characterized by the severity of albuminuria and cardiovascular disorders. Approximately 20 to 40% of the global prevalence of DN is mostly reported to occur in individuals with diabetes, and nearly 28% of DN occurs in individuals with other renal disorders. The pathological mechanism is very complex, involving innumerable targets and leading to multiple pharmacological effects. Thus, the scientific community is forced to work in search of safe and potent therapeutics that can tackle the complex pathology of DN effectively. The secondary plant metabolites categorized as terpenoids gained attention as potential therapeutics contrary to others for the management of diabetic nephropathy and other associated syndromes by their strong antioxidant activity and inhibition of advanced glycation and its associated products. This review focused on herbal therapeutics for the management of diabetic nephropathy. Moreover, different types of terpenoids, their biological sources, and proposed mechanisms of action are explored for the development of a novel pharmacophore for diabetic nephropathy.

Perspective of Secondary Metabolites in Respect of Multidrug Resistance (MDR): A Review.

Aberrant and haphazard use of antibiotics has created the development of antimicrobial resistance which is a bizarre challenge for human civilization. This emerging crisis of antibiotic resistance for microbial pathogens is alarming all the nations posing a global threat to human health. It is difficult to treat bacterial infections as they develop resistance to all antimicrobial resistance. Currently used antibacterial agents inhibit a variety of essential metabolic pathways in bacteria, including macro-molecular synthesis (MMS) pathways (e.g. protein, DNA, RNA, cell wall) most often by targeting a specific enzyme or subcellular component e.g. DNA gyrase, RNA polymerase, ribosomes, transpeptidase. Despite the availability of diverse synthetic molecules, there are still many complications in managing progressive and severe antimicrobial resistance. Currently not even a single antimicrobial agent is available for which the microbes do not show resistance. Thus, the lack of efficient drug molecules for combating microbial resistance requires continuous research efforts to overcome the problem of multidrug-resistant bacteria. The phytochemicals from various plants have the potential to combat the microbial resistance produced by bacteria, fungi, protozoa and viruses without producing any side effects. This review is a concerted effort to identify some of the major active phytoconstituents from various medicinal plants which might have the potential to be used as an alternative and effective strategy to fight against microbial resistance and can promote research for the treatment of MDR.

AmpC Inhibition: An Explicit Approach against Multi-Drug Resistance (MDR).

Multi-drug resistance and its transmission is a ubiquitous health issue worldwide. The beta-lactamase AmpC resistance is a major concern among all health settings like hospitals and child care centers, etc. The clinical pipeline of the new antibiotics remains dry due to the production of AmpC beta-lactamases by the bacteria to develop resistance against antibiotics. According to the global antimicrobial resistance and use surveillance system, the rate of resistance to ciprofloxacin an antibiotic commonly used to treat urinary tract infections, varied from 8.4% to 92.9% for Escherichia coli and from 4.1% to 79.4% for Klebsiellapneumoniae in different countries. The lack of comprehensiveness within the data makes a choice problematic for the selection of appropriate ß-lactam antibiotic for the treatment of resistant microorganisms. Most experts agree it is prudent to avoid expanded-spectrum (i.e. third-generation) cephalosporins for the treatment of organisms posing the greatest risk of AmpC induction. Nonetheless, the development of specific inhibitors for the AmpC enzyme, either naturally or synthetically, is only unfolding. To date, there is no single and clinically active drug available that inhibits the AmpC enzyme and combats multidrug resistance and its transmission in individuals. The deficit of the enzyme inhibitor focused the researchers to work in the area. This present review will emphasize on the chemistry, and structure of clinically important and potent inhibitors against AmpC enzymes.

The use of medium cutoff dialyzers in patients with multiple myeloma and acute kidney injury requiring hemodialysis: A systematic review.

BACKGROUND: Patients with multiple myeloma and high serum levels of circulating free light chains (FLC) have increased risk of acute kidney injury (AKI) secondary to cast nephropathy and is associated with poor survival. Despite removal of FLC by medium cutoff (MCO) dialyzer, the role of MCO hemodialysis (HD) in the treatment of cast nephropathy and its clinical benefits remain unknown. METHODS: A systematic review was conducted to establish the effectiveness of MCO dialyzer and clinical outcomes, compared to other forms of dialyzers in the removal of FLC, in myeloma patients with AKI. The primary outcome was effectiveness of MCO-HD in reducing serum FLC. The secondary outcomes were HD independence, estimated glomerular filtrate rate, mortality rates, length of hospitalization, rebound of serum FLC before the next dialysis, removal of other molecules during dialysis, and adverse events. RESULTS: We identified three case series, with a total of 17 patients. There were no randomized controlled trials (RCTs) or cohort studies. These case series showed that MCO dialyzer was effective in the removal of FLC and led to a reduction in FLC concentration post-dialysis. The majority of the case series did not have comparator arm and renal and/or other clinical outcomes. CONCLUSION: MCO dialyzer appeared to be effective in the removal of FLC based on the existing limited data. However, more data, particularly large-scale RCTs, are needed to assess the use of MCO dialyzer in reducing serum FLC and its effect on clinical outcomes in patients with multiple myeloma and AKI.

Non-steroidal anti-inflammatory drugs in chronic kidney disease and risk of acute adverse kidney events according to route of administration.

BACKGROUND: Topical non-steroidal anti-inflammatory drugs (NSAIDs) have lower risks for cardiovascular disease and gastrointestinal adverse effects compared to oral NSAIDs, but there are little data regarding their kidney risks in chronic kidney disease (CKD). We evaluated the risk of adverse acute kidney outcomes in CKD according to route of NSAID administration. METHODS: Retrospective cohort study of adults with CKD (eGFR less than 60 ml/min/1.73 m2) who received prescriptions between 2015 and 2017 from a major healthcare cluster in Singapore. The adverse acute kidney outcomes were acute kidney injury (AKI) and need for nephrology specialist consult within 30 days. RESULTS: Among 6298 adults with CKD (mean age 72.1 ± 13.3 years and eGFR 41.9 ± 12.2 ml/min/1.73 m2), systemic and topical NSAIDs were prescribed in 16.7% and 32.0%, respectively. Incident AKI (any severity), KDIGO Stage 2 or 3 AKI, and need for nephrology specialist consult occurred in 16.7%, 2.6%, and 10.6% of the study cohort, respectively. After adjusting for age, diabetes, recent cardiovascular hospitalization, baseline eGFR, RAAS blocker and diuretic, systemic NSAIDs, and topical NSAIDs, compared with the no-NSAID group, were independently associated with incident AKI [adjusted OR 1.77 (95% CI 1.46-2.15) and 1.38 (1.18-1.63), respectively]. Moderate and severe AKI (adjusted OR 1.68, 95% CI 1.09-2.58, p = 0.02) and need for nephrology consults (adjusted OR 1.41, 95% CI 1.09-1.82, p = 0.008) were also increased in systemic NSAIDs. CONCLUSION: Among adults with CKD, both systemic and topical NSAIDs were independently associated with acute adverse kidney outcomes.

Neutrophil gelatinase-associated lipocalin: a biochemical marker for acute kidney injury and long-term outcomes in patients presenting to the emergency department.

Introduction: Creatinine has limitations in identifying and predicting acute kidney injury (AKI). Our study examined the utility of neutrophil gelatinase-associated lipocalin (NGAL) in predicting AKI in patients presenting to the emergency department (ED), and in predicting the need for renal replacement therapy (RRT), occurrence of major adverse cardiac events (MACE) and all-cause mortality at three months post visit. Methods: This is a single-centre prospective cohort study conducted at Singapore General Hospital (SGH). Patients presenting to SGH ED from July 2011 to August 2012 were recruited. They were aged ≥21 years, with an estimated glomerular filtration rate <60 mL/min/1.73 m2, and had congestive cardiac failure, systemic inflammatory response syndrome or required hospital admission. AKI was diagnosed by researchers blinded to experimental measurements. Serum NGAL was measured as a point-of-care test. Results: A total of 784 patients were enrolled, of whom 107 (13.6%) had AKI. Mean serum NGAL levels were raised (P < 0.001) in patients with AKI (670.0 ± 431.9 ng/dL) compared with patients without AKI (490.3 ± 391.6 ng/dL). The sensitivity and specificity of NGAL levels >490 ng/dL for AKI were 59% (95% confidence interval [CI] 49%-68%) and 65% (95% CI 61%-68%), respectively. Need for RRT increased 21% per 100 ng/dL increase in NGAL (P < 0.001), whereas odds of death in three months increased 10% per 100 ng/dL increase in NGAL (P = 0.028). No clear relationship was observed between NGAL levels and MACE. Conclusion: Serum NGAL identifies AKI and predicts three-month mortality.

Regional citrate anticoagulation vs systemic heparin anticoagulation for double-filtration plasmapheresis.

INTRODUCTION: Double-filtration plasmapheresis (DFPP) has been utilized for immunomodulation in kidney transplantation. Anticoagulation is important to maintain circuit patency during DFPP. We aimed to compare the efficacy and safety of regional citrate anticoagulation (RCA) with systemic heparin anticoagulation during DFPP in kidney transplant recipients. METHODS: A retrospective cohort study was conducted to compare the efficacy and safety of RCA (RCA-DFPP) to systemic heparin anticoagulation (Hep-DFPP) for DFPP among kidney transplant recipients in a single tertiary center. RESULTS: A total of 112 sessions of DFPP were performed for 23 subjects, of which 62 sessions were RCA-DFPP and 50 sessions were Hep-DFPP. There were 13 sessions (11.6%) of premature circuit clotting, 10 sessions (16.1%) for RCA-DFPP and 3 sessions (6.0%) for Hep-DFPP (P = .10). All premature circuit clotting episodes occurred in subjects who underwent DFPP through a vascular catheter. Premature circuit clotting was associated with the use of a vascular catheter (odds ratio [OR] 14.2, 95% confidence interval [CI] 2.7-73.7; P < .01) and high postfilter ionized calcium (OR 12.7, 95% CI 1.4-112.5; P < .01). There was no major bleeding event. Hep-DFPP was associated with higher occurrence of hypocalcemia (OR 1.1, 95% CI 1.0-1.2; P < .01) and metabolic acidosis (OR 1.4, 95% CI 1.2-2.0; P = .04), while hypomagnesemia was more common for RCA-DFPP (OR 2.9, 95% CI 1.1-7.4; P = .03). CONCLUSION: Amongst kidney transplant patients who receive DFPP therapy, RCA-DFPP may be comparable to Hep-DFPP for the maintenance of circuit patency. Functioning vascular access is vital in avoiding premature clotting of the circuit. Close monitoring of electrolyte imbalances and coagulopathy related to DFPP is recommended.

Algal rhodopsins encoding diverse signal sequence holds potential for expansion of organelle optogenetics.

Rhodopsins have been extensively employed for optogenetic regulation of bioelectrical activity of excitable cells and other cellular processes across biological systems. Various strategies have been adopted to attune the cellular processes at the desired subcellular compartment (plasma membrane, endoplasmic reticulum, Golgi, mitochondria, lysosome) within the cell. These strategies include-adding signal sequences, tethering peptides, specific interaction sites, or mRNA elements at different sites in the optogenetic proteins for plasma membrane integration and subcellular targeting. However, a single approach for organelle optogenetics was not suitable for the relevant optogenetic proteins and often led to the poor expression, mislocalization, or altered physical and functional properties. Therefore, the current study is focused on the native subcellular targeting machinery of algal rhodopsins. The N- and C-terminus signal prediction led to the identification of rhodopsins with diverse organelle targeting signal sequences for the nucleus, mitochondria, lysosome, endosome, vacuole, and cilia. Several identified channelrhodopsins and ion-pumping rhodopsins possess effector domains associated with DNA metabolism (repair, replication, and recombination) and gene regulation. The identified algal rhodopsins with diverse effector domains and encoded native subcellular targeting sequences hold immense potential to establish expanded organelle optogenetic regulation and associated cellular signaling.

Regional Citrate Anticoagulation during Double-Filtration Plasmapheresis in Kidney Transplant Recipients: A Single-Center Retrospective Cohort Study.

INTRODUCTION: Double-filtration plasmapheresis (DFPP) may be used for immunomodulation in kidney transplant (KTx). While DFPP reduces plasma product exposure, risk of circuit clotting merits adequate anticoagulation. Regional citrate anticoagulation (RCA) avoids the risks of systemic anticoagulation, but a protocol for RCA-DFPP is not previously widely described. METHODS: We conducted a single-center retrospective cohort study involving adult (≥21 years old) KTx recipients who underwent RCA-DFPP from 2018 to 2020 to investigate efficacy and safety for an RCA protocol during DFPP in KTx recipients. RESULTS: Fifty-one (85%) of 60 RCA-DFPP sessions in 17 patients completed without circuit clotting. Circuit clotting was associated with high post-filter ionized calcium (28 vs. 3.7%, odds ratio 10.1, 95% CI 1.1-89.4, p = 0.037). Hypo- and hypercalcemia developed in 5 (8.3%) and 8 (13.3%) sessions, respectively, but no adverse effects were noted despite severe hypocalcemia in one. There was no significant change in pre- and post-RCA-DFPP sodium, bicarbonate, albumin, and platelet levels. With regards DFPP procedure, prolongation of prothrombin time (PT) and activated partial thromboplastin time (aPTT) was observed following 38 (64.4%) and 12 (20.3%) sessions, respectively. Severely prolonged (>1.5 × upper limit normal) PT and aPTT were recorded in 2 sessions each. Expectedly, hypofibrinogenemia developed after 31 (51.7%) sessions: including 4 (6.7%) severe hypofibrinogenemia (<0.5 g/L). Two patients developed bleeding requiring blood product transfusion. The median total volume of fluids administered per session was 1.495 (1.373-1.612) L; post-RCA-DFPP significant weight gain of 0.5 (0-1.25) kg was noted. Diuretic was commenced or dose increased following 20 (33.3%) sessions for fluid balance management. DISCUSSION/CONCLUSION: Protocol-based RCA for DFPP is feasible and safe in KTx recipients. However, DFPP-related coagulopathy can develop consequent to treatment; caution should be exercised for patients with bleeding risk. Close monitoring and management of the patients' electrolytes, especially hypocalcemia and hypomagnesemia, and fluid status is recommended.

Non-Steroidal Anti-Inflammatory Drugs and Risk of Acute Kidney Injury and Hyperkalemia in Older Adults: A Retrospective Cohort Study and External Validation of a Clinical Risk Model.

AIM: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used analgesics among older adults. Adverse effects may be avoided by careful patient selection. We aimed to evaluate the incidence of acute kidney injury (AKI) and/or hyperkalemia, risk factors, and the accuracy of an NSAID risk prediction model in a cohort of Asian older adults. METHODS: We conducted a retrospective cohort study of older adults, age 65 years and above, who received prescriptions between March 2015 and December 2017 from Singapore's largest cluster of public healthcare institutions. Factors associated with 30-day incident acute kidney injury and/or hyperkalemia were evaluated with multivariable regression analysis. Calibration and discrimination of the Nash prediction model were assessed using the Hosmer-Lemeshow goodness-of-fit test and C-statistic, respectively. RESULTS: The primary outcome occurred in 16.7% of 12,798 older adults. Topical NSAIDs (adjusted OR 1.29, 95% CI 1.15-1.45), systemic NSAIDs of 1-14 days' duration (adjusted OR 1.43, 95% CI 1.27-1.62), and systemic NSAIDs > 14 days (adjusted OR 1.84, 95% CI 1.37-2.49) were independently associated with the primary outcome, compared with no NSAID. Diabetes mellitus, cardiovascular disease, lower estimated glomerular filtration rate (eGFR), and diuretics were also independently associated with increased incident AKI and/or hyperkalemia. When applied to older adults with systemic NSAIDs > 14 days (n = 305), the Nash risk model had poor calibration (p < 0.001) and poor discrimination with C-statistic 0.527 (0.438, 0.616). CONCLUSIONS: Longer NSAID duration and systemic compared with topical route were associated with incremental odds for acute renal events. Further studies are required to improve the available risk model to guide NSAID prescriptions in older adults.

Classification of Uremic Toxins and Their Role in Kidney Failure.

Advances in our understanding of uremic retention solutes, and improvements in hemodialysis membranes and other techniques designed to remove uremic retention solutes, offer opportunities to readdress the definition and classification of uremic toxins. A consensus conference was held to develop recommendations for an updated definition and classification scheme on the basis of a holistic approach that incorporates physicochemical characteristics and dialytic removal patterns of uremic retention solutes and their linkage to clinical symptoms and outcomes. The major focus is on the removal of uremic retention solutes by hemodialysis. The identification of representative biomarkers for different classes of uremic retention solutes and their correlation to clinical symptoms and outcomes may facilitate personalized and targeted dialysis prescriptions to improve quality of life, morbidity, and mortality. Recommendations for areas of future research were also formulated, aimed at improving understanding of uremic solutes and improving outcomes in patients with CKD.

Hypertriglyceridemia-induced pancreatitis in pregnancy: case review on the role of therapeutic plasma exchange.

SUMMARY: Gestational hypertriglyceridemia-induced pancreatitis is associated with significant maternal and fetal morbidity and mortality. We report a case of gestational hypertriglyceridemia-induced pancreatitis in a primigravida at 31-weeks gestation, complicated by impending preterm labor and metabolic acidosis requiring hemodialysis. This was successfully managed with therapeutic plasma exchange (TPE), followed by i.v. insulin, low-fat diet, and omega-3. Triglyceride levels stabilized after TPE and the patient underwent an uncomplicated term delivery. In pregnancy, elevated estrogen and insulin resistance exacerbate hypertriglyceridemia. Management is challenging as risks and benefits of treatment options need to be weighed against fetal wellbeing. We discuss management options including a review of previous case reports detailing TPE use, dietary optimization, and delivery timing. This case emphasizes the importance of multidisciplinary care to optimize maternal and fetal outcomes. LEARNING POINTS: Gestational hypertriglyceridemia-induced pancreatitis has high morbidity. A multidisciplinary team approach is a key as maternal and fetal needs must be addressed. Rapid lowering of triglycerides is crucial and can be achieved successfully and safely with plasma exchange. A low-fat diet while ensuring adequate nutrition in pregnancy is important. Timing of delivery requires consideration of fetal maturity and risk of recurrent pancreatitis.

Mucociliary Respiratory Epithelium Integrity in Molecular Defense and Susceptibility to Pulmonary Viral Infections.

Mucociliary defense, mediated by the ciliated and goblet cells, is fundamental to respiratory fitness. The concerted action of ciliary movement on the respiratory epithelial surface and the pathogen entrapment function of mucus help to maintain healthy airways. Consequently, genetic or acquired defects in lung defense elicit respiratory diseases and secondary microbial infections that inflict damage on pulmonary function and may even be fatal. Individuals living with chronic and acute respiratory diseases are more susceptible to develop severe coronavirus disease-19 (COVID-19) illness and hence should be proficiently managed. In light of the prevailing pandemic, we review the current understanding of the respiratory system and its molecular components with a major focus on the pathophysiology arising due to collapsed respiratory epithelium integrity such as abnormal ciliary movement, cilia loss and dysfunction, ciliated cell destruction, and changes in mucus rheology. The review includes protein interaction networks of coronavirus infection-manifested implications on the molecular machinery that regulates mucociliary clearance. We also provide an insight into the alteration of the transcriptional networks of genes in the nasopharynx associated with the mucociliary clearance apparatus in humans upon infection by severe acute respiratory syndrome coronavirus-2.

Cross-sectional study on the role of public awareness in preventing the spread of COVID-19 outbreak in India.

BACKGROUND: WHO has recommended personal hygiene (respiratory hygiene, using face masks, washing hands with warm water and soap, use of alcohol-based hand sanitizers, avoid touching mouth, eyes & nose, cleanliness), social distancing and careful handling of purchased products as an effective preventive measure for COVID-19 disease. The growing pandemic of COVID-19 disease requires social distancing and personal hygiene measures to protect public health. But this message is not clear and well understood among people. The aim of this study is to determine the awareness, knowledge and attitude about COVID-19 and relate the behaviour of Indian society, especially when the country is restarting all its economic activities, after the complete lockdown. METHOD: The present paper is based on an extensive survey among 21 406 adult participants of various sections of Indian society with different age groups between 18 and 80 years to introspect the level of public awareness with respect to cause, spread, prevention and treatment of disease caused by spread of COVID-19 viral outbreak, which will be automatically reflected in the societal behavioural response of rigorous precautionary measures. CONCLUSIONS: There is a need to extend the knowledge base among individuals to enhance their active participation in the prevention mechanisms with respect to the spread of the pandemic. There is a need to elaborate the Indian socio-cultural aspects, so that society starts appreciating and voluntarily following social distancing. This should improve the adaptability of people with livelihood resilience to let them protect themselves not only from the present pandemic but also from all other unforeseen infections, and to provide care to patients.

IgG4-Related Disease with Selective Testicular Involvement- A Rare Entity: Case Report with Review of Literature.

Immunoglobin-G4 related disease (IgG4-RD) is an auto-immune inflammatory condition where patients present with a tumour-like mass that shows infiltration by plasma cell and subsequent fibrosis. It is a systemic condition that primarily involves the salivary glands, pancreas, kidneys, aorta, and retroperitoneum amongst other organs. Testicular involvement is a rare occurrence in this disease entity. A 55-year old male patient presented with the complaints of pain and swelling in the right scrotal region. Right-sided orchidectomy was carried out which on histopathology showed features suggestive of IgG4-RD which was later confirmed on immunohistochemistry. Whole body MRI revealed that no other organ was involved in the disease process in this patient. IgG4-RD has a variable clinical course and considerable overlap with its differentials. Imaging studies and serum IgG4 levels are neither confirmatory nor customarily diagnostic in every case. The only confirmatory diagnostic investigation is histopathological examination, which shows infiltration of IgG4+ plasma cells and fibrosis in the involved tissue. Whenever a mass-forming lesion with typical histomorphological features is encountered with involvement of multiple organs/anatomic sites, IgG4-related disease should be considered among the differentials, and clinicians of all disciplines should be familiar with this disease entity.

Description of parallel and sequential configurations for concurrent therapeutic plasma exchange and continuous kidney replacement therapy in adults.

Therapeutic plasma exchange (TPE) and continuous kidney replacement therapy (CKRT) are extracorporeal therapeutic procedures often implemented in management of patients. Critically ill patients may be afflicted with disease processes that require both TPE and CKRT. Performing TPE discontinuous with CKRT is technically easier, however, it disrupts CKRT and may compromise with CKRT efficiency or hemofilter life. Concurrent TPE with CKRT offers several advantages including simultaneous control of disease process and correction of electrolyte, fluid, and acid-base disturbances that may accompany TPE. Additionally, TPE may be performed by either centrifugation method or membrane plasma separation method. The technical specifications of these methods may influence the methodology of concurrent connections. This report describes and reviews two different approaches to circuit arrangements when establishing concurrent TPE and CKRT.

Novel Modular Rhodopsins from Green Algae Hold Great Potential for Cellular Optogenetic Modulation Across the Biological Model Systems.

Light-gated ion channel and ion pump rhodopsins are widely used as optogenetic tools and these can control the electrically excitable cells as (1) they are a single-component system i.e., their light sensing and ion-conducting functions are encoded by the 7-transmembrane domains and, (2) they show fast kinetics with small dark-thermal recovery time. In cellular signaling, a signal receptor, modulator, and the effector components are involved in attaining synchronous regulation of signaling. Optical modulation of the multicomponent network requires either receptor to effector encoded in a single ORF or direct modulation of the effector domain through bypassing all upstream players. Recently discovered modular rhodopsins like rhodopsin guanylate cyclase (RhoGC) and rhodopsin phosphodiesterase (RhoPDE) paves the way to establish a proof of concept for utilization of complex rhodopsin (modular rhodopsin) for optogenetic applications. Light sensor coupled modular system could be expressed in any cell type and hence holds great potential in the advancement of optogenetics 2.0 which would enable manipulating the entire relevant cell signaling system. Here, we had identified 50 novel modular rhodopsins with variant domains and their diverse cognate signaling cascades encoded in a single ORF, which are associated with specialized functions in the cells. These novel modular algal rhodopsins have been characterized based on their sequence and structural homology with previously reported rhodopsins. The presented novel modular rhodopsins with various effector domains leverage the potential to expand the optogenetic tool kit to regulate various cellular signaling pathways across the diverse biological model systems.

Ensuring Sustainability of Continuous Kidney Replacement Therapy in the Face of Extraordinary Demand: Lessons From the COVID-19 Pandemic.

With the exponential surge in patients with coronavirus disease 2019 (COVID-19) worldwide, the resources needed to provide continuous kidney replacement therapy (CKRT) for patients with acute kidney injury or kidney failure may be threatened. This article summarizes subsisting strategies that can be implemented immediately. Pre-emptive weekly multicenter projections of CKRT demand based on evolving COVID-19 epidemiology and routine workload should be made. Corresponding consumables should be quantified and acquired, with diversification of sources from multiple vendors. Supply procurement should be stepped up accordingly so that a several-week stock is amassed, with administrative oversight to prevent disproportionate hoarding by institutions. Consumption of CKRT resources can be made more efficient by optimizing circuit anticoagulation to preserve filters, extending use of each vascular access, lowering blood flows to reduce citrate consumption, moderating the CKRT intensity to conserve fluids, or running accelerated KRT at higher clearance to treat more patients per machine. If logistically feasible, earlier transition to intermittent hemodialysis with online-generated dialysate, or urgent peritoneal dialysis in selected patients, may help reduce CKRT dependency. These measures, coupled to multicenter collaboration and a corresponding increase in trained medical and nursing staffing levels, may avoid downstream rationing of care and save lives during the peak of the pandemic.