Time Trends in Causes of Death in People With HIV: Insights From the Swiss HIV Cohort Study.

BACKGROUND: Advancements in access to antiretroviral therapy (ART) and human immunodeficiency virus (HIV) care have led to a decline in AIDS-related deaths among people with HIV (PWH) in Switzerland. However, data on the ongoing changes in causes of death among PWH over the past 15 years are scarce. METHODS: We investigated all reported deaths in the Swiss HIV Cohort Study between 2005 and 2022. Causes of death were categorized using the Coding Causes of Death in HIV protocol. The statistical analysis included demographic stratification to identify time trends and logistic regression models to determine associated factors for the underlying cause of death. RESULTS: In total, 1630 deaths were reported, with 23.7% of individuals assigned female sex at birth. These deaths included 147 (9.0%) HIV/AIDS-related deaths, 373 (22.9%) due to non-AIDS, non-hepatic cancers, 166 (10.2%) liver-related deaths, and 158 (9.7%) cardiovascular-related deaths. The median age at death (interquartile range) increased from 45.0 (40.0-53.0) years in 2005-2007 to 61.0 (56.0-69.5) years in 2020-2022. HIV/AIDS- and liver-related deaths decreased, whereas deaths from non-AIDS, non-hepatic cancers increased and cardiovascular-related deaths remained relatively stable. CONCLUSIONS: The proportionally decreasing HIV/AIDS and liver-related deaths showcase the effectiveness of ART, comprehensive HIV patient care, and interventions targeting hepatitis C virus coinfection. Future research should focus on managing cancer and cardiovascular-related conditions as the new leading causes of death among PWH. Comprehensive healthcare strategies focusing on non-AIDS-related comorbid conditions, cancer management, and sustaining liver and cardiovascular health are needed to bridge the ongoing health disparities between PWH and the general population.

Stromal DLK1 promotes proliferation and inhibits differentiation of the intestinal epithelium during development.

The stem/progenitor cells of the developing intestine are biologically distinct from their adult counterparts. Here, we examine the microenvironmental cues that regulate the embryonic stem/progenitor population, focusing on the role of Notch pathway factor delta-like protein-1 (DLK1). mRNA-seq analyses of intestinal mesenchymal cells (IMCs) collected from embryonic day 14.5 (E14.5) or adult IMCs and a novel coculture system with E14.5 intestinal epithelial organoids were used. Following addition of recombinant DLK1 (rDLK) or Dlk1 siRNA (siDlk1), epithelial characteristics were compared using imaging, replating efficiency assays, qPCR, and immunocytochemistry. The intestinal phenotypes of littermate Dlk1+/+ and Dlk1-/- mice were compared using immunohistochemistry. Using transcriptomic analyses, we identified morphogens derived from the embryonic mesenchyme that potentially regulate the developing epithelial cells, to focus on Notch family candidate DLK1. Immunohistochemistry indicated that DLK1 was expressed exclusively in the intestinal stroma at E14.5 at the top of emerging villi, decreased after birth, and shifted to the intestinal epithelium in adulthood. In coculture experiments, addition of rDLK1 to adult IMCs inhibited organoid differentiation, whereas Dlk1 knockdown in embryonic IMCs increased epithelial differentiation to secretory lineage cells. Dlk1-/- mice had restricted Ki67+ cells in the villi base and increased secretory lineage cells compared with Dlk1+/+ embryos. Mesenchyme-derived DLK1 plays an important role in the promotion of epithelial stem/precursor expansion and prevention of differentiation to secretory lineages in the developing intestine.NEW & NOTEWORTHY Using a novel coculture system, transcriptomics, and transgenic mice, we investigated differential molecular signaling between the intestinal epithelium and mesenchyme during development and in the adult. We show that the Notch pathway factor delta-like protein-1 (DLK1) is stromally produced during development and uncover a new role for DLK1 in the regulation of intestinal epithelial stem/precursor expansion and differentiation to secretory lineages.

Similarities and differences in tissue distribution of DLK1 and DLK2 during E16.5 mouse embryogenesis.

DLK1 and DLK2 are transmembrane proteins belonging to the EGF-like repeat-containing family that function as non-canonical NOTCH inhibitory ligands. DLK1 is usually downregulated after embryo development and its distribution in some adult and embryonic tissues has been described. However, the expression and role of DLK2 in embryo and adult tissues remains unclear. To better understand the relevance of both proteins during embryo development, we analyzed the expression pattern of DLK1 and DLK2 in 16.5-day-old mouse embryos (E16.5) and evaluated the possible relationship between these two proteins in embryo tissues and cell types. We found that DLK1 and DLK2 proteins exhibited a broad distribution pattern, which was detected in developing mouse organs from each of the three germ layers: ectoderm (brain, salivary glands), mesoderm (skeletal muscle, vertebral column, kidney, cartilage), and endoderm (thymus, lung, pancreas, intestine, liver). The expression pattern of DLK1 and DLK2 indicates that both proteins could play a synergistic role during cell differentiation. This study provides additional information for understanding temporal and site-specific effects of DLK1 and DLK2 during embryo morphogenesis and cell differentiation.

Correction to: Similarities and differences in tissue distribution of DLK1 and DLK2 during E16.5 mouse embryogenesis.

In the original publication of the article, some symbols in Figure 3 were not correctly aligned with the image.

Substance P and Calcitonin gene-related peptide expression in human periodontal ligament after root canal preparation with Reciproc Blue, WaveOne Gold, XP EndoShaper and hand files.

AIM: To quantify Substance P (SP) and Calcitonin gene-related peptide (CGRP) expression in healthy human periodontal ligament from premolars after root canal preparation with Reciproc Blue, WaveOne Gold, XP EndoShaper and hand files. METHODOLOGY: A total of 50 human periodontal ligament samples were obtained from healthy mandibular premolars where extraction was indicated for orthodontic reasons. Prior to extraction, 40 of these premolars were equally divided into four groups, and root canals were prepared using four different systems: Reciproc Blue, WaveOne Gold, XP EndoShaper and a hand instrumentation technique. The remaining 10 healthy premolars were extracted without treatment and served as a negative control group. All periodontal ligament samples were processed, and SP and CGRP were measured by radioimmunoassay. The Kruskal-Wallis test was used to establish significant differences between groups and LSD post hoc comparisons were also performed. RESULTS: Greater SP and CGRP values were found in the hand instrumentation group, followed by the XP EndoShaper, WaveOne Gold and the Reciproc groups. The lower SP and CGRP values were for the healthy periodontal ligament group. The Kruskal-Wallis test revealed significant differences between groups (P < 0.05). Post hoc Least Significant Difference (LSD) tests revealed significant differences (P < 0.05) in SP and CGRP expression between all the comparisons except for the Reciproc Blue and WaveOne Gold group (P > 0.05). CONCLUSION: All the root canal preparation techniques tested increased SP and CGRP expression in human periodontal ligament, with hand files and XP EndoShaper instruments being associated with greater neuropeptide release compared to Reciproc Blue and WaveOne Gold files.

Reduced salivary gland size and increased presence of epithelial progenitor cells in DLK1-deficient mice.

DLK1 (PREF1, pG2, or FA1) is a transmembrane and secreted protein containing epidermal growth factor-like repeats. Dlk1 expression is abundant in many tissues during embryonic and fetal development and is believed to play an important role in the regulation of tissue differentiation and fetal growth. After birth, Dlk1 expression is abolished in most tissues but is possibly reactivated to regulate stem cell activation and responses to injury. We have recently reported that DLK1 regulates many aspects of salivary gland organogenesis. Here, we have extended our studies of the salivary gland phenotype of Dlk1 knock-out mice. We have observed that salivary glands are smaller and weigh significantly less in both Dlk1 knock-out males and females compared with gender and age-matched wild-type mice and regardless of the natural sexual dimorphism in rodent salivary glands. This reduced size correlates with a reduced capacity of Dlk1-deficient mice to secrete saliva after stimulation with pilocarpine. However, histological and ultrastructural analyses of both adult and developing salivary gland tissues have revealed no defects in Dlk1 ((-/-)) mice, indicating that genetic compensation accounts for the relatively mild salivary phenotype in these animals. Finally, despite their lack of severe anomalies, we have found that salivary glands from Dlk1-deficient mice present a higher amount of CK14-positive epithelial progenitors at various developmental stages, suggesting a role for DLK1 in the regulation of salivary epithelial stem cell balance.

An expandable prosthesis with dual cage-and-plate function in a single device for vertebral body replacement: the clinical experience on 14 consecutive cases with vertebral tumors.

AIM: The aim of this paper was to test the hypothesis that an expandable prosthesis with dual cage-and-plate function can provide immediate and durable spine stabilization after corpectomy. METHODS: We designed an expandable vertebral body prosthesis with dual cage-and-plate function in a single device (JR-prosthesis). Anatomical studies were performed to design a titanium-made prosthesis. Cadaver assays were done with a stainless steal device to test fixation and adequacy to the human spine anatomy. Then, 14 patients with vertebral tumors (8 metastatic) underwent corpectomy and vertebral body replacement with the JR-prosthesis. RESULTS: All patients had neurological deficit, severe pain and spine instability (mean follow-up: 25.4 months). Mean pain score before surgery in a visual analog scale improved from 7.6 to 3.0 points after operation (P=0.002). All patients achieved at least one grade of improvement in the Frankel score (P=0.003), excepting the 3 patients with Frankel grade A presurgery. Two patients with renal cell carcinoma died during the following 4 days after surgery (renal failure and massive bleeding), the rest attained a painless and stable spine immediately and maintained for long periods. No significant infections or implant failures were registered. A non-fatal case of inferior vena cava surgical injury was observed (repaired during surgery without further complications). CONCLUSION: The JR-prosthesis stabilizes the spine immediately after surgery and for the rest of the patients' life. To our knowledge, this is the first report on the clinical experience of any expandable vertebral body prosthesis with dual cage-and-plate function in a single device. These observations await confirmation in different scenarios.

Electronic and optical competence of TiO2/BiVO4 nanocomposites in the photocatalytic processes.

Nanocomposites with different ratios of titanium dioxide and bismuth vanadate [TiO2]/[BiVO4] give rise to compatible electronic band structure alignment at their interfaces to ensure enhanced photoactivated charge transfer under visible light. The sol-gel method and suitable post-synthesis thermal treatments were used to synthesize different compositions with stabilized anatase phase of TiO2 and monoclinic scheelite polymorph BiVO4. Structural, electronic and optical characterizations were performed and the results were analysed as a function of the stoichiometry, in which both crystalline structures show a clear junction formation among their characteristic stacking planes. Photocatalytic and (photo) electrochemical responses of the nanocomposites were investigated and tested for the degradation of azo dyes (Acid Blue-113, AB-113) (~ 99%) under visible light radiation. The nanocomposite with a mass ratio of (1:10) shows the highest photocatalytic efficiency compared to the other compositions. HRTEM images showed marked regions in which both crystalline structures form a clear junction and their characteristic planes. However, the increase of BiVO4 content in the network overcomes the photocatalytic activity due to the decrease in the reduction potential of the photo-generated electrons with high recombination rates.

Comparing two high correlation models to test the mechanical stability of americium-II.

In this work two high density functional theory (DFT) correlation methodologies, the so called DFT+U (or GGA+U) implementation and the exact exchange of correlated electrons (EECE), hybrid DFT functional (or one case of hybrid DFT), are tested to determine the mechanical properties of americium-II. For each case, the numeric value of their principal parameter is chosen ([Formula: see text] for the first case and [Formula: see text] for the second one) once the crystalline structure meets all the mechanical stability conditions. The results show that there is a range of values of [Formula: see text] and [Formula: see text] in which both methodologies generate a stable (experimentally correct) non-magnetic ground state, reaching approximately the same numeric value of the set of elastic constants of the cubic structure. However, only for the case of the hybrid functional results it is possible to show how the non-magnetic configuration is energetically favored, as compared to the ferromagnetic configuration. This happens around [Formula: see text], a value in agreement with a previous analysis made under the same methodology for the metal case Am-I. Following a detailed and deep analysis, it is possible to find a close interrelation between the electronic properties of the metal: its distribution of states around the Fermi level, the energy difference between the two possible spin configurations, and the mechanical response of the crystal. Also, it is possible to conclude that the effect of alpha parameter on the [Formula: see text] electrons can be used as a parameter to simulate the presence of an external pressure over the structure. For the comparison, the calculations were performed within the LAPW approximation in DFT as implemented in the WIEN2k code, with a finite deformation method.

Rapid phosphorylation of Ets-2 accompanies mitogen-activated protein kinase activation and the induction of heparin-binding epidermal growth factor gene expression by oncogenic Raf-1.

Heparin-binding epidermal growth factor (HB-EGF) gene transcription is rapidly activated in NIH 3T3 cells transformed by oncogenic Ras and Raf and mediates the autocrine activation of the c-Jun N-terminal kinases (JNKs) observed in these cells. A 1.7-kb fragment of the promoter of the murine HB-EGF gene linked to a luciferase reporter was strongly induced following activation of deltaRaf-1:ER, a conditionally active form of oncogenic human Raf-1. Promoter activation by deltaRaf-1:ER required a composite AP-1/Ets transcription factor binding site located between bp -974 and -988 upstream of the translation initiation site. In vivo genomic footprinting indicated that the basal level of occupancy of this composite AP-1/Ets element increased following deltaRaf-1:ER activation. Cotransfection of Ets-2 and p44 mitogen-activated protein (MAP) kinase expression vectors strongly potentiated HB-EGF promoter activation in response to deltaRaf-1:ER. Potentiated activation required both p44 MAP kinase catalytic activity and threonine 72 in the Pointed domain of Ets-2. Biochemical assays demonstrated the ability of the p42 and p44 MAP kinases to phosphorylate Ets-2 on threonine 72. Importantly, in intact cells, the kinetics of phosphorylation of Ets-2 on this residue closely mirror the activation of the p42 and p44 MAP kinases and the observed onset of HB-EGF gene transcription following deltaRaf-1:ER activation. These data firmly establish Ets-2 as a direct target of the Raf-MEK-MAP kinase signaling pathway and strongly implicate Ets-2 in the regulation of HB-EGF gene expression.

Progressive unilateral damage of the entorhinal cortex enhances synaptic efficacy of the crossed entorhinal afferent to dentate granule cells.

Progressive injury to the mammalian CNS often reduces the severity of lesion-induced deficits or spares the behavior from deficits altogether. The mechanism(s) underlying this behavioral sparing is not clearly understood, but axonal sprouting is a likely candidate. To test this possibility, unilateral, two-stage (progressive) lesions of the entorhinal cortex, which are known to accelerate sprouting by the crossed temporodentate pathway and spare spatial memory function, were made in rats. We examined the changes in synaptic efficacy (as measured by the amplitude and slope of evoked population EPSPs) of the crossed temporodentate projection after either one-stage or progressive unilateral lesions of the entorhinal area. Whereas the synaptic efficacy of the one-stage group did not differ significantly from the control group at 4, 6, or 8 d after the lesion, the synaptic efficacy of the crossed temporodentate pathway in the progressive lesion group significantly increased above the control values as early as 4 d after the lesion and remained stable thereafter. Axonal sprouting thus may provide a mechanism by which to account for behavioral sparing after progressive brain damage.

Theoretical z -pinch scaling relations for thermonuclear-fusion experiments.

We have developed wire-array z -pinch scaling relations for plasma-physics and inertial-confinement-fusion (ICF) experiments. The relations can be applied to the design of z -pinch accelerators for high-fusion-yield (approximately 0.4 GJ/shot) and inertial-fusion-energy (approximately 3 GJ/shot) research. We find that (delta(a)/delta(RT)) proportional (m/l)1/4 (Rgamma)(-1/2), where delta(a) is the imploding-sheath thickness of a wire-ablation-dominated pinch, delta(RT) is the sheath thickness of a Rayleigh-Taylor-dominated pinch, m is the total wire-array mass, l is the axial length of the array, R is the initial array radius, and gamma is a dimensionless functional of the shape of the current pulse that drives the pinch implosion. When the product Rgamma is held constant the sheath thickness is, at sufficiently large values of m/l, determined primarily by wire ablation. For an ablation-dominated pinch, we estimate that the peak radiated x-ray power P(r) proportional (I/tau(i))(3/2)Rlphigamma, where I is the peak pinch current, tau(i) is the pinch implosion time, and phi is a dimensionless functional of the current-pulse shape. This scaling relation is consistent with experiment when 13 MA < or = I < or = 20 MA, 93 ns < or = tau(i) < or = 169 ns, 10 mm < or = R < or = 20 mm, 10 mm < or = l < or = 20 mm, and 2.0 mg/cm < or = m/l < or = 7.3 mg/cm. Assuming an ablation-dominated pinch and that Rlphigamma is held constant, we find that the x-ray-power efficiency eta(x) congruent to P(r)/P(a) of a coupled pinch-accelerator system is proportional to (tau(i)P(r)(7/9 ))(-1), where P(a) is the peak accelerator power. The pinch current and accelerator power required to achieve a given value of P(r) are proportional to tau(i), and the requisite accelerator energy E(a) is proportional to tau2(i). These results suggest that the performance of an ablation-dominated pinch, and the efficiency of a coupled pinch-accelerator system, can be improved substantially by decreasing the implosion time tau(i). For an accelerator coupled to a double-pinch-driven hohlraum that drives the implosion of an ICF fuel capsule, we find that the accelerator power and energy required to achieve high-yield fusion scale as tau(i)0.36 and tau(i)1.36, respectively. Thus the accelerator requirements decrease as the implosion time is decreased. However, the x-ray-power and thermonuclear-yield efficiencies of such a coupled system increase with tau(i). We also find that increasing the anode-cathode gap of the pinch from 2 to 4 mm increases the requisite values of P(a) and E(a) by as much as a factor of 2.

Diurnal and spatial (vertical) dynamics of nutrients (N, P, Si) in four sampling days (summer, fall, winter, and spring) in a tropical shallow reservoir and their relationships with the phytoplankton community.

The vertical and diurnal variation of nitrogen and phosphorus forms, as well as that of soluble reactive silica (SRS), were studied in four sampling days at Gar9as reservoir, a shallow tropical one located in the city of São Paulo, in southeastern Brazil. Except for N-NH4, all other inorganic forms of nitrogen (N-NO2, N-NO3, and total N) demonstrated decreased concentrations toward the bottom of reservoir. Similarly, all showed significant diurnal differences on every sampling day, with increased values during the night due to absence of photosynthetic assimilation during that period. In the sampling days, these forms decreased on the spring sampling day due to the bloom of Microcystis registered during this period of the year. All three forms of phosphorus (SRP, particulate P, and total P) showed significant vertical variation, except on the fall sampling day. On the summer sampling day there was an increase of both total P and particulate P, the latter because it constitutes more than 70% of the total P during all sampling days. Hourly phosphorus variation was significant during all sampling days, except for the summer one. The SRS vertical variation was significant during all sampling days, except for that in the spring. It was also different hourly on sampling days.

The role of axonal sprouting in functional reorganization after CNS injury: lessons from the hippocampal formation.

Functional reorganization is often invoked to account for recovery of function after central nervous system (CNS) injury. The mechanisms underlying this possible reorganization, however, remain uncertain. In the last 30 years, studies of the hippocampal formation of rats have indicated that the CNS is capable of undergoing significant changes in its pattern of connectivity in response to injury. Here, we explore numerous examples of lesion-induced alterations in hippocampal connectivity known as axonal sprouting. Both homotypic and heterotypic sprouting occur in the denervated hippocampus after unilateral entorhinal cortex lesions. We assess the behavioral relevance of glutamatergic homotypic sprouting emerging from the surviving contralateral entorhinal area (i.e., the crossed temporodentate projection) as well as the heterotypic sprouting from the remaining surviving afferents (e. g., the cholinergic septodentate pathway) to the hippocampus. Studies examining the role of crossed temporodentate sprouting in recovery from memory deficits after entorhinal cortex injury indicate that homotypic sprouting may indeed contribute to a reorganization of cortical function resulting in recovered mnemonic capacity. Heterotypic sprouting is not as clearly linked to recovery of function after bilateral entorhinal injury. We propose a tripartite model for functional reorganization based on homotypic sprouting, neurotrophic factors, and altered inhibitory functioning to account for how relatively small increases in surviving homotypic pathways might restore neurological function.

The effects of Neotrofin on septodentate sprouting after unilateral entorhinal cortex lesions in rats.

PURPOSE: Recent research on the purine derivative of hypoxanthine Neotrofin (4-[[3-(1,6-dihydro-6-oxo-9-purin-9-yl)-1-oxopropyl]amino]benzoic acid; AIT-082) has indicated that Neotrofin treatment elevates the mRNA levels of various neurotrophic factors, including nerve growth factor (NGF), in the CNS. Several previous studies have indicated that NGF may regulate septodentate sprouting after entorhinal cortex lesions in rats. Thus, the objective of this investigation was to determine whether Neotrofin treatment would enhance lesion-induced septodentate sprouting from 4 to 15 days postlesion. METHODS: Sham-operated rats or rats with EC lesions were injected (i.p.) with either Neotrofin (30 mg/kg) or saline (0.9%) immediately after surgery and every day thereafter until the end of the treatment regimen. Septodentate sprouting, as indicated by intensity of acetylcholinesterase (AChE) label in the dentate gyrus, was assessed with optical densitometry. RESULTS: We observed that Neotrofin elevated the AChE-label in the outer molecular layer of the ventral dentate gyrus at 4 days postlesion and of the dorsal dentate gyrus at 15 days postlesion. CONCLUSIONS: Neotrofin appears to have exerted limited stimulatory effects on lesion-induced sprouting by a cholinergic pathway.

Basic fibroblast growth factor enhances axonal sprouting after cortical injury in rats.

The trophic factors responsible for initiating and guiding the outgrowth of axons have proven to be elusive throughout most of this century. Entorhinal cortex injury, which denervates the hippocampal formation of rats, induces axonal sprouting by several surviving hippocampal afferents and results in a significant elevation of growth factors, one of which is basic fibroblast growth factor (bFGF). The possibility that bFGF may regulate lesion-induced hippocampal sprouting was examined by making i.v. bFGF infusions into rats with unilateral entorhinal lesions. Basic FGF treatment significantly increased sprouting by the cholinergic septodentate pathway. Thus, the increase in bFGF following central nervous system injury may signal its role in the regulation of injury-related axonal remodeling of a cholinergic pathway.

Sparing and recovery of spatial alternation performance after entorhinal cortex lesions in rats.

Groups of adult rats were first trained on a spatial alternation task and then subjected to unilateral entorhinal cortex lesions, unilateral entorhinal cortex lesions followed by dorsal psalterium transections, or bilateral entorhinal cortex lesions. After this surgery, the rats were then tested for retention of spatial alternation. Neither unilateral lesions alone nor unilateral lesions followed by dorsal psalterium transections resulted in long-term spatial performance deficits; however, animals with bilateral lesions exhibited severe impairments from which they eventually recovered. The results from animals with bilateral entorhinal damage indicate that extensive postoperative training may facilitate the recovery of spatial alternation performance. Histological analyses indicated that the crossed entorhinal projection proliferated in the dentate gyrus after unilateral entorhinal lesions and such anomalous growth occurred independently of any changes in alternation performance.

Enhanced recovery of learned alternation in ganglioside-treated rats after unilateral entorhinal lesions.

The present study demonstrates that an abbreviated regimen of ganglioside treatments attenuates the behavioral impairments produced by unilateral lesions of the entorhinal cortex. Ganglioside treatments not only accelerate recovery of learned alternation on a Y-maze, but also reduce total errors and perseverative errors.

Recovery from perseverative behavior after entorhinal cortex lesions in rats.

In a previous investigation we observed that entorhinal cortex lesions produce an impairment in spatial alternation characterized by repeated responses in one direction (i.e. 'perseveration'). Since this impairment disappears at the same time when the dentate gyrus is reinnervated by several of its remaining afferents, recovery from perseveration and sprouting may be related. To test this possibility, we examined the performance of two groups of rats with bilateral entorhinal lesions: one group began testing for retention of an alternation task on day 2 after the lesions; the other group began on day 12 (i.e. the time at which hippocampal sprouting occurs). Both groups exhibited significantly greater perseveration than their respective sham-operated groups over the first 6-12 days of testing. Thus, postoperative testing was required to facilitate the shift from perseverative to non-perseverative responding independent of the time at which sprouting in the dentate gyrus became established.

Neonatal brain damage and recovery: intraventricular injection of NGF at time of injury alters performance of active avoidance.

Rats were given lesions of either the ventromedial hypothalamus (VMH) or septal nucleus at 7 days of age and then were tested repeatedly in an active avoidance task (A.A.) from 20 to 80 days. VMH rats were consistently impaired on the A.A. task beginning at 40 days of age. The animals with septal lesions performed the A.A. task consistently better than VMH or control animals throughout the entire test period, the septal syndrome becoming more pronounced as the rats reached maturity. In intact rats a single, intraventricular injection of NGF given at 7 days of age resulted in a greater reactivity, especially as the rats approached maturity. NGF, given at time of surgery, also improved performance of the A.A. task in VMH-damaged rats tested at 40-80 days. In rats given septal lesions, NGF treatment at time of injury attenuated the septal syndrome of improved A.A. performance. The data indicate that NGF treatment, given to neonatal rats, can produce long-lasting effects on CNS functions and can contribute to functional recovery from brain lesions.