Treatment of hypoplastic left heart syndrome: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: This meta-analysis aimed to consolidate existing data from randomised controlled trials on hypoplastic left heart syndrome. METHODS: Hypoplastic left heart syndrome specific randomised controlled trials published between January 2005 and September 2021 in MEDLINE, EMBASE, and Cochrane databases were included. Regardless of clinical outcomes, we included all randomised controlled trials about hypoplastic left heart syndrome and categorised them according to their results. Two reviewers independently assessed for eligibility, relevance, and data extraction. The primary outcome was mortality after Norwood surgery. Study quality and heterogeneity were assessed. A random-effects model was used for analysis. RESULTS: Of the 33 included randomised controlled trials, 21 compared right ventricle-to-pulmonary artery shunt and modified Blalock-Taussig-Thomas shunt during the Norwood procedure, and 12 regarded medication, surgical strategy, cardiopulmonary bypass tactics, and ICU management. Survival rates up to 1 year were superior in the right ventricle-to-pulmonary artery shunt group; this difference began to disappear at 3 years and remained unchanged until 6 years. The right ventricle-to-pulmonary artery shunt group had a significantly higher reintervention rate from the interstage to the 6-year follow-up period. Right ventricular function was better in the modified Blalock-Taussig-Thomas shunt group 1-3 years after the Norwood procedure, but its superiority diminished in the 6-year follow-up. Randomised controlled trials regarding medical treatment, surgical strategy during cardiopulmonary bypass, and ICU management yielded insignificant results. CONCLUSIONS: Although right ventricle-to-pulmonary artery shunt appeared to be superior in the early period, the two shunts applied during the Norwood procedure demonstrated comparable long-term prognosis despite high reintervention rates in right ventricle-to-pulmonary artery shunt due to pulmonary artery stenosis. For medical/perioperative management of hypoplastic left heart syndrome, further randomised controlled trials are needed to deliver specific evidence-based recommendations.

Subtle membrane changes in cryopreserved bull spermatozoa when modified temperature drop rates are used during the first phase of freezing.

BACKGROUND: Cryopreservation of spermatozoa involves reduction of temperature to a subzero level, leading to increased longevity. However, temperature reduction has a significant effect on sperm membranes. OBJECTIVE: To evaluate the impact of the rate of temperature drop during the first phase of freezing on subtle membrane changes in cryopreserved bull spermatozoa. MATERIALS AND METHODS: Thirty-two ejaculates from four bulls (eight ejaculates/bull) were collected using artificial vagina while keeping a 3 to 4 days gap between two collections. Diluted semen samples were equilibrated at 5 degree C for 4 hours. The samples were then placed in a pre-programmed semen freezer. The first phase of freezing, that is, 5 degree C till -10 degree C was subjected to three different temperature drop rates: accelerated (F1), moderate (F2), and slow (F3), at 20 degree C per min, 10 degree C per min and 5 degree C per min, respectively. After thawing, spermatozoa were assessed for percentage live, plasma, and acrosomal membrane integrity, along with the external appearance of phosphatidyl serine, indicating apoptosis. RESULTS: A significant difference (p < 0.05) in viability, plasma membrane integrity (HOS test), and acrosome membrane integrity (PSA test) was observed between F3 and the other groups. However, the parameters did not significantly differ between F1 and F2. The annexin V-PI assay (AN/PI) categorized four types of sperm populations: non-apoptotic and viable (AN-/PI-), apoptotic and viable (AN+/PI-), non-apoptotic and non-viable (AN-/PI+), and apoptotic and non-viable (AN+/PI+). The proportion of spermatozoa with (AN-/PI-) and (AN+/PI+) differed significantly (p < 0.05) between F3 and the other groups. The values for apoptotic and viable (AN+/PI-) and non-apoptotic and non-viable (AN-/PI+) sperm were not significantly different among all freezing categories. CONCLUSION: A slower temperature drop rate (freezing rate) during the first phase of freezing results in less damaging, subtle membrane changes. Doi.org/10.54680/fr24410110312.

Architectural analysis of root system and phytohormone biosynthetic genes expression in wheat (Triticum aestivum L.) inoculated with Penicillium oxalicum.

In this study, a fungal plant growth promoter Penicillium oxalicum T4 isolated from non-rhizosphere soil of Arunachal Pradesh, India, was screened for different plant growth promoting traits in a gnotobiotic study. Though inoculation improved the overall growth of the plants, critical differences were observed in root architecture. Confocal Laser Scanning Microscope, Scanning electron microscope and the stereo microscopic study showed that inoculated wheat plants could develop profuse root hairs as compared to control. Root scanning indicated improvement in cumulative root length, root area, root volume, number of forks, links, crossings, and other parameters. A confocal scanning laser microscope indicated signs of endophytic colonization in wheat roots. Gene expression studies revealed that inoculation of T4 modulated the genes affecting root hair development. Significant differences were marked in the expression levels of TaRSL4, TaEXPB1, TaEXPB23, PIN-FORMED protein, kaurene oxidase, lipoxygenase, ACC synthase, ACC oxidase, 9-cis-epoxycarotenoid dioxygenase, and ABA 8'-hydroxylase genes. These genes contribute to early plant development and ultimately to biomass accumulation and yield. The results suggested that P. oxalicum T4 has potential for growth promotion in wheat and perhaps also in other cereals.

Effectiveness of a Cognitive Behavioral Randomized Controlled Trial for People Living with HIV Who are Heavy Drinkers: The Holistic Health Recovery Program (HHRP) Trial in Miami.

This study evaluates the impact of an intervention targeting high-risk behaviors among diverse, alcohol-using adults living with HIV (N = 267) from 2009 to 2013 in Miami, FL. The intervention took place in a group setting for eight sessions over 4 weeks and was compared to a didactic health promotion group. Assessments were conducted pre-intervention, post-intervention, and at 3, 6, and 12 months follow-up. Intervention participants (48% of sample) evidenced greater knowledge about HIV, more condom self-efficacy, and greater intentions to use condoms after participation. This was particularly noteworthy because associations among knowledge about HIV, more condom self-efficacy, and greater intentions to use condoms were negatively associated with intervention status at baseline. Participants also reported fewer heavy drinking days after participating in the intervention than those in the control group. Greater HIV knowledge, more condom self-efficacy and intentions to use condoms predicted more condom assertiveness; greater intentions to use condoms predicted fewer unprotected sexual behaviors. These findings underscore the importance of taking a comprehensive, multi-systemic approach to address risky behaviors in high-risk, diverse populations.

Synthesis, biological evaluation, and molecular docking study of some new rohitukine analogs as protein tyrosine phosphatase 1B inhibitors.

Rohitukine (RH) was extracted from the stem bark of Dysoxylum binectariferum Hook. It was derivatized to different arylsulphanmides by treating with the corresponding aryl sulphonyl chlorides. These derivatives were tested in-vitro on protein tyrosine phosphatase 1B (PTP1B) inhibition. Among these the active compounds K2, K3, K5, and K8 significantly inhibited the PTP1B by 51.3%, 65.6%, 71.9%, and 55.9% respectively at 10 µg/ml, the results were also supported by in-silico docking experiments. The most potent compound K5 was analyzed for antidiabetic and antidyslipidemic activity in vivo. It showed a marked reduction in blood glucose level (random and fasting) and serum insulin level in db/db mice. It improved glucose intolerance as ascertained by the oral glucose tolerance test (OGTT). These NCEs (New Chemical Entities) also lowered cholesterol and triglyceride profiles while improved high-density lipoprotein cholesterol in db/db mice. The K5 was further evaluated for antiadipogenic activity on MDI (Methylisobutylxanthine, dexamethasone, and insulin)-induced adipogenesis. where it significantly inhibited MDI-induced adipogenesis in 3 T3-L1 preadipocytes, at 10 µM and 20 µM concentration. These results were compared with the parent compound RH which inhibited 35% and 45% lipid accumulation while the RH analog K5 inhibited the lipid accumulation by 41% and 51% at 10 and 20 µM concentration, respectively. These results well corroborated with in-silico studies.

Imaging of the spectrum of abnormal systemic arterial supply to the lungs using dual-source CT.

Abnormal systemic arterial supply to the lungs can be seen in various congenital and acquired diseases. Identification and characterisation of aberrant vascular supply is essential for further management and treatment. Multidetector computed tomography (CT) with its multiplanar capabilities and volume-rendering techniques provides precise information regarding the anatomy and spatial relationship of arterial vascular channels. The following concise review elucidates the characteristic imaging findings of conditions in which systemic arteries are seen supplying the lung parenchyma on dual-source CT.

JSCO-ESMO-ASCO-JSMO-TOS: international expert consensus recommendations for tumour-agnostic treatments in patients with solid tumours with microsatellite instability or NTRK fusions.

A Japan Society of Clinical Oncology (JSCO)-hosted expert meeting was held in Japan on 27 October 2019, which comprised experts from the JSCO, the Japanese Society of Medical Oncology (JSMO), the European Society for Medical Oncology (ESMO), the American Society of Clinical Oncology (ASCO), and the Taiwan Oncology Society (TOS). The purpose of the meeting was to focus on what we have learnt from both microsatellite instability (MSI)/deficient mismatch repair (dMMR) biomarkers in predicting the efficacy of anti-programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) immunotherapy, and the neurotrophic tyrosine receptor kinase (NTRK) gene fusions in predicting the efficacy of inhibitors of the tropomyosin receptor kinase (TRK) proteins across a range of solid tumour types. The recent regulatory approvals of the anti-PD-1 antibody pembrolizumab and the TRK inhibitors larotrectinib and entrectinib, based on specific tumour biomarkers rather than specific tumour type, have heralded a paradigm shift in cancer treatment approaches. The purpose of the meeting was to develop international expert consensus recommendations on the use of such tumour-agnostic treatments in patients with solid tumours. The aim was to generate a reference document for clinical practice, for pharmaceutical companies in the design of clinical trials, for ethics committees in the approval of clinical trial protocols and for regulatory authorities in relation to drug approvals, with a particular emphasis on diagnostic testing and patient selection.

Electrically controlled topological micro cargo transportation.

We demonstrate electrically controlled linear translation and precision positioning of a colloidal particle in a soft matter device. The basis of transportation is the time dependent electric field reconfiguration and manipulation of a topological line defect between two distinct hybrid aligned nematic liquid crystal domains having opposing tilt orientations. Deliberately tuning an applied voltage relative to a low threshold value (5.7 V at 1 kHz) permits defect trapping of the colloidal particle and allows subsequent control over the particle's velocity and bidirectional linear movement over millimeter distances, without the need for externally imposed flow nor for lateral confining walls.

Bacillus species in soil as a natural resource for plant health and nutrition.

The genus Bacillus is one of the predominant bacterial genera found in soil, and several species of this genus have been reported from diverse ecological niches. Endowed with tremendous genetic and metabolic diversity, Bacillus spp. serve multiple ecological functions in soil ecosystem from nutrient cycling to conferring stress tolerance to plants. Members of the genus Bacillus are known to have multiple beneficial traits which help the plants directly or indirectly through acquisition of nutrients, overall improvement in growth by production of phytohormones, protection from pathogens and other abiotic stressors. This functionally versatile genus is one of the most commercially exploited bacteria in the agro-biotechnology industry. Still its potential has not been realized sufficiently and requires an emphasis towards translating the relevant technologies from laboratory to land for the benefit of mankind.

Avalanches and Criticality in Driven Magnetic Skyrmions.

We show using numerical simulations that slowly driven Skyrmions interacting with random pinning move via correlated jumps or avalanches. The avalanches exhibit power-law distributions in their duration and size, and the average avalanche shape for different avalanche durations can be scaled to a universal function, in agreement with theoretical predictions for systems in a nonequilibrium critical state. A distinctive feature of Skyrmions is the influence of the nondissipative Magnus term. When we increase the ratio of the Magnus term to the damping term, a change in the universality class of the behavior occurs, the average avalanche shape becomes increasingly asymmetric, and individual avalanches exhibit motion in the direction perpendicular to their own density gradient.

Compression of a giant pseudomeningocele causing transient anoxic seizures-a case report.

Transient anoxic seizure upon application of pressure on a giant pseudomeningocele has never been reported in the literature; such abrupt changes in intracranial pressure due to large volume of cerebrospinal fluid (CSF) translocation, if left untreated may lead to permanent cerebral hypoxic injury and death. Here we describe a case of a 26-year-old woman who had undergone lumbar disc surgery in another unit few months ago and developed a large lump around her back. Any pressure on the lump resulted in headaches and at times episodes of seizures. Clinical examination revealed a very large fluid-filled lump consistent with a giant pseudomeningocele, confirmed by an MRI. A video EEG while applying pressure on the lump was recorded. The patient developed a typical seizure attack with a characteristic pattern of cerebral anoxia, and a paired ECG showed irregular rhythm with junctional and ventricular ectopic beats during the latter part of the attack, raising a suspicion of asystole. Upon relieving the pressure off the lump, the patient gradually regained consciousness with no permanent neurological deficit. We then discuss the pathophysiology of anoxic seizures and highlight the need to be vigilant in managing patients with such lesions in order to prevent permanent cerebral hypoxic injury and death.

Effect of Cholesterol-loaded Cyclodextrin on Membrane and Acrosome Status of Hariana Bull Sperm during Cryopreservation.

BACKGROUND: The membrane and acrosomal integrity of sperm play a vital role in fertilization process; however they are compromised upon cryopreservation. OBJECTIVE: To study the effect of cholesterol-loaded cyclodextrin (CLC) on membrane and acrosome status of Hariana bull sperm during cryopreservation. MATERIALS AND METHODS: Semen samples collected from Hariana bulls with mass motility ≥ 3+ and individual progressive motility ≥ 70% were utilized in the study. Each ejaculate was split into two parts, one part being evaluated freshly for various seminal attributes and the other part being diluted in Tris diluent (without egg yolk and glycerol) to obtain a final concentration of 120×106 sperm/mL. The diluted semen was divided into four treatments: Group I, without CLC (control); Group II, with CLC at 0.5 mg per 120 million sperm; Group III, at 1.0 mg per 120 million sperm; Group IV, at 2.0 mg per 120 million sperm. All aliquots were incubated for 15 min at 37°C and each sample was diluted with Egg yolk-Tris-Glycerol (EYTG) extender up to 80×106 sperm/mL. The diluted semen samples were packed in French mini straws (0.25 mL), sealed and equilibrated at 4°C for 4 h followed by cryopreservation. The samples at pre-freeze and post-thaw stage were evaluated for membrane and acrosomal integrity, as well as primary, secondary and tertiary acrosomal damages. RESULTS: The membrane and acrosomal integrity was significantly higher in group II as compared to groups I, III, and IV, at pre-freeze and post-thaw stage (P<0.05). The primary and secondary acrosomal damage were significantly reduced in group II compared to other groups (P<0.05). No significant difference in tertiary acrosomal damage was found among different groups. CONCLUSION: CLC improves the membrane and acrosomal integrity, and reduces primary and secondary acrosomal damages during cryopreservation of Hariana bull sperm.

Seasonal Variation in Helminth Parasites of Snakeheads Channa Punctatus and Channa Striatus (Perciformes: Channidae) in Uttar Pradesh, India.

Snakehead fishes are widely consumed throughout South East Asia, China and India because of their good taste of meat and high nutrient values such as presence of prostaglandins, thromboxane and Omega-6 fatty acid. Parasitic infection constitutes significant economic loss in fish production. The aim of this work was to study the seasonal variation of helminths in snakeheads. In the presented study, a three-year survey has been performed. A total of 1013 individuals of Channa punctatus and 247 individuals of Channa striatus were examined. A total of 3783 helminths were collected, with an average of 3.02 helminths/fish. 43.50 % individuals of C. punctatus and 59.10 % of C. striatus were found to be infected with acanthocephalans, trematodes, nematodes and cestodes per year. The prevalence and mean abundance of Pallisentis sp. was at its peak in summer. However the prevalence of trematodes, nematodes and cestodes was at peak during autumn. Mean abundance of nematodes was at peak in summer. Interestingly, the males were found more infected as compared to the females and the infection rate in males peaked in summer. In comparison to other weight groups, medium size hosts (21 - 40 g) were found more consistently infected. Thus the results indicate that there are seasonal variations in parasitic helminths infecting C. punctatus and C. striatus which also depend upon sex and weight. These variations may be attributed to various environmental and biological factors including parasite life cycle and immune level of host.

Exonal switch down-regulates the expression of CD5 on blasts of acute T cell leukaemia.

To date, CD5 expression and its role in acute T cell lymphoblastic leukaemia (T-ALL) have not been studied closely. We observed a significant reduction in surface expression of CD5 (sCD5) on leukaemic T cells compared to autologous non-leukaemic T cells. In this study, we have shown the molecular mechanism regulating the expression and function of CD5 on leukaemic T cells. A total of 250 patients suffering from leukaemia and lymphoma were immunophenotyped. Final diagnosis was based on their clinical presentation, morphological data and flow cytometry-based immunophenotyping. Thirty-nine patients were found to be of ALL-T origin. Amplification of early region of E1A and E1B transcripts of CD5 was correlated with the levels of surface and intracellular expression of CD5 protein. Functional studies were performed to show the effect of CD5 blocking on interleukin IL-2 production and survival of leukaemic and non-leukaemic cells. Lack of expression of sCD5 on T-ALL blasts was correlated closely with predominant transcription of exon E1B and significant loss of exon E1A of the CD5 gene, which is associated with surface expression of CD5 on lymphocytes. High expression of E1B also correlates with increased expression of cytoplasmic CD5 (cCD5) among leukaemic T cells. Interestingly, we observed a significant increase in the production of IL-2 by non-leukaemic T cells upon CD5 blocking, leading possibly to their increased survival at 48 h. Our study provides understanding of the regulation of CD5 expression on leukaemic T cells, and may help in understanding the molecular mechanism of CD5 down-regulation.

Effect of Yb doping on the refractive index and thermo-optic coefficient of YVO4 single crystals.

Single crystals of YVO4 with different doping concentrations of Yb (1.5, 3.0, 8.0, and 15.0 at. %) and with good crystalline quality (FWHM ∼43-55 arc sec of rocking curve) were grown by the optical floating zone technique. Refractive index measurements were carried out at four wavelengths as a function of temperature. The measurements show that as the doping concentration of Yb is increased, the refractive index varies marginally for ne whereas there is a significant change in the value of no. The thermo-optic coefficient (dn/dT) was found to be positive with a value ∼10-5/°C, which is 1 order higher than that for the undoped YVO4 crystal. The thermo-optic coefficient is higher for ne compared to that of no. Also, a set of relations describing the wavelength dependence of the thermo-optic coefficient were established that are useful for calculating the thermo-optic coefficient at any temperature in the range 30°C-150°C and at any wavelength in the range 532-1551 nm.

Preparation of NGF encapsulated chitosan nanoparticles and its evaluation on neuronal differentiation potentiality of canine mesenchymal stem cells.

Sustained and controlled release of neurotrophic factors in target tissue through nanomaterial based delivery system could be a better strategy for nerve tissue regeneration. The present study aims to prepare the nerve growth factor (NGF) encapsulated chitosan nanoparticles (NGF-CNPs) and its evaluation on neuronal differentiation potentiality of canine bone marrow derived mesenchymal stem cells (cBM-MSCs). The NGF-CNPs were prepared by ionotropic gelation method with tripolyphosphate (TPP) as an ionic cross-linking agent. Observations on physiochemical properties displayed the size of nanoparticles as 80-90 nm with positive zeta potential as well as an ionic interaction between NGF and nanoparticle. NGF loading efficiency was found to be 61% while its sustained release was observed by an in vitro release kinetics study. These nanoparticles were found to be cytocompatible to cBM-MSCs when supplemented at a concentration upto 4 mg/ml in culture media. The NGF-CNP supplemented culture media was able to transdifferentiate the preinduced cBM-MSCs into neurons in a better way than unbound NGF supplementation. Further, it was also noticed that NGF-CNPs were able to transdifferentiate cBM-MSCs without any chemical based preinduction. In conclusion, our findings propose that NGF-CNPs are capable of releasing bioactive NGF with the ability to transdifferentiate mesenchymal stem cells into neurons, suggesting its potential future application in nerve tissue regeneration.

Evaluation of Metabolic Syndrome and Vitamin D Receptor Gene Polymorphism in Male Factor Infertility.

Male factor infertility (MFI) is a growing health issue in society. The vitamin D receptor gene (VDR) is expressed in many tissues and modulates expression of several other genes. The purpose of this study was to investigate the association between MetSyn, VDR gene (FokI, rs-2228570; C > T) polymorphisms and MFI in Indian adults. Fifty cases and fifty-four controls, fulfilling inclusion and exclusion criteria, were included with their informed consent. Fasting plasma glucose, triglyceride, HDL-C were estimated by clinical chemistry analyzer (Beckmam Coulter DXC 800, USA). Serum insulin was measured by electrochemiluminescence immunoassay and VDR gene polymorphism by RFLP-PCR. Statistical analysis was done using SPSS 20.0. MetSyn was more frequent in MFI cases than controls. There was significant difference between waist circumference, fasting plasma glucose, triglycerides in MFI cases and controls. There was significant difference in HOMA-IR between MFI cases and controls (p value < 0.05) and serum insulin was significantly raised in MFI cases (p value < 0.05). VDR gene polymorphism was found to be associated with MFI cases as compared to controls and the serum level of vitamin D was also decreased in MFI cases than in controls (p value < 0.05). This study provides evidence that insulin resistance is more in MFI cases than in controls and occurrence of MetSyn and its components is higher in MFI cases than in controls. Our findings provide evidence that VDR gene (FokI, rs-2228570; C > T) polymorphism increases the risk of male factor infertility.

Mapping of protein-protein interaction network of Alexander disease.

Alexander disease (ALXD) is slowly progressive neurodegenerative disorder which affects white matter of the central nervous system. The main cause of disorder is mutation in GFAP gene and mutation in some other genes were also reported. This study was aimed at getting a better insight into ALXD pathogenesis and identifying the important functional and highly interconnected nodes in human protein interaction network, identifying the important sub-networks in the system could be helpful in understanding the underlying molecular mechanism. The topological analysis of human protein interaction network strategy to identify highly interconnected sub-network modules from which six proteins are found i.e. GFAP, PLEC, CRYAB, NDUFV1, CASP3 and MAPK14 plays important role in disease. Further, the enrichment analysis of interaction network identifies crucial pathways in which most of the diseased proteins overlaps. Through system biology approach, the undirected human protein interaction network of ALXD is buildup with the help of Cytoscape tool and its various plugins helps to investigate network further. The systematic approach suggests the finding of previously known proteins, GFAP, PLEC, CRYAB, NDUFV1, CASP3 and MAPK14 can be used as a drug targets and potential treatment discovered also enrichment analysis will provide guidance for the future study on Alexander disease.

Isolation and characterization of Lepidoptera specific Bacillus thuringiensis strains predominantly from north-eastern states of India.

Both, the tobacco caterpillar Spodoptera litura (Fabricius) and the cotton bollworm Helicoverpa armigera (Hibner), are serious polyphagous pests causing considerable loss to crops. Indiscriminate use of chemical pesticides for controlling them has rather resulted in their resistance development. Microbial pesticides, Bacillus thuringiensis in particular, play an important role in pest management. Here, we isolated Bacillus thuringiensis-like bacteria from the soil samples primarily collected from North East region of India along with some states viz., Haryana, Punjab, Maharashtra, West Bengal and Uttarakhand and studied their toxicity against the above two insect pests at 10 gg/g along with standard strain B. thuringiensis subsp. kurstaki HD-I and at 1 pg/g Pseudomonasfluorescens based MVPII expressing CrylAc toxin and AUG-5. Isolates AUG-5 and GTG-7 proved toxic to more than 75% larvae on the 4h as well as 7h day of the treatment of the neonates of H. armigera. The AUG-5 isolate was also effective against S. litura. Ten effective isolates (AUG-5, GTG-4, GTG-7, GTG-9, GTG-42, GTG-64, GTG-70, GTG-3S, GTG-4S and GTG-6S) were characterized using biochemical and 16S rDNA analysis. Nearly, all the isolates tested positive for utilizing monosaccharides. All selected B. thuringiensis isolates showed resistance to ampicillin and co-trimoxazole except AUG-5 to- co-trimoxazole. AUG-5 and GTG-7 were highly toxic to both insects, and possessed cryl, cry1A and cry2 genes. These isolates AUG-5 and GTG-7 also contained high CrylAc (104.8 and 88.32 ng/mg) and Cry2Ab (3792 and 1305.9 ng/mg), respectively in their spore-crystal complex. Both, AUG-5 and GTG-7 isolates, could be considered for further development as bioinsecticides. The present study has established the diversity and richness of B. thuringiensis-like isolates in soils collected from north-eastern region of India.

When linear stability does not exclude nonlinear instability.

We describe a mechanism that results in the nonlinear instability of stationary states even in the case where the stationary states are linearly stable. This instability is due to the nonlinearity-induced coupling of the linearization's internal modes of negative energy with the continuous spectrum. In a broad class of nonlinear Schrödinger equations considered, the presence of such internal modes guarantees the nonlinear instability of the stationary states in the evolution dynamics. To corroborate this idea, we explore three prototypical case examples: (a) an antisymmetric soliton in a double-well potential, (b) a twisted localized mode in a one-dimensional lattice with cubic nonlinearity, and (c) a discrete vortex in a two-dimensional saturable lattice. In all cases, we observe a weak nonlinear instability, despite the linear stability of the respective states.