Systematic review and meta-analysis of birth weight and PFNA exposures.

We used a systematic review that included risk of bias and study sensitivity analysis to identify 34 studies examining changes in birth weight (BWT) in relation to PFNA biomarker measures (e.g., maternal serum/plasma or umbilical cord samples). We fit a random effects model of the overall pooled estimate and stratified estimates based on sample timing and overall study confidence. We conducted a meta-regression to further examine the impact of gestational age at biomarker sample timing. We detected a -32.9 g (95%CI: -47.0, -18.7) mean BWT deficit per each ln PFNA increase from 27 included studies. We did not detect evidence of publication bias (pE = 0.30) or between-study heterogeneity in the summary estimate (pQ = 0.05; I2 = 36%). The twelve high confidence studies yielded a smaller pooled effect estimate (ß = -28.0 g; 95%CI: -49.0, -6.9) than the ten medium (ß = -39.0 g; 95%CI: -61.8, -16.3) or four low (ß = -36.9 g; 95%CI: -82.9, 9.1) confidence studies. The stratum-specific results based on earlier pregnancy sampling periods in 11 studies showed smaller deficits (ß = -22.0 g; 95%CI: -40.1, -4.0) compared to 10 mid- and late-pregnancy (ß = -44.2 g; 95%CI: -64.8, -23.5) studies and six post-partum studies (ß = -42.9 g; 95%CI: -88.0, 2.2). Using estimates of the specific gestational week of sampling, the meta-regression showed results consistent with the categorical sample analysis, in that as gestational age at sampling time increases across these studies, the summary effect estimate of a mean BWT deficit got larger. Overall, we detected mean BWT deficits for PFNA that were larger and more consistent across studies than previous PFAS meta-analyses. Compared to studies with later sampling, BWT deficits were smaller but remained sizeable for even the earliest sampling periods. Contrary to earlier meta-analyses for PFOA and PFOS, BWT deficits that were detected across all strata did not appear to be fully explained by potential bias due to pregnancy hemodynamics from sampling timing differences.

Clinical and cost-effectiveness of physiotherapy interventions following total knee replacement: a systematic review and meta-analysis.

PURPOSE: Osteoarthritis is the single most common cause of pain and disability in older adults. This review addresses the question of the clinical effectiveness and cost-effectiveness of physiotherapy interventions following total knee replacement (TKR). METHODS: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. MEDLINE, CINAHL, AMED, DARE, HTA and NHS EED databases were searched from inception to 02 May 2020. Search terms related to the clinical and cost-effectiveness of physiotherapy interventions were used. Studies meeting the inclusion criteria were identified and key data were extracted. Random effect meta-analysis was conducted for pain, physical function and range of motion (ROM). RESULTS: In total, 1467 studies were identified. Of these, 26 studies were included; methodological quality of most studies was adequate. Physiotherapy interventions were more effective than control for function, SMD - 0.166 [95% Confidence Interval (CI) - 0.420 to 0.088.] and ROM, SMD - 0.219 [95% CI - 0.465 to 0.028] for a follow-up of 2 or 3 months. Patients in the intervention group showed improvement in pain at 12-13 weeks, SMD - 0.175 [95% CI - 0.416 to 0.067]. No evidence on the pooled estimate of cost-effectiveness of physiotherapy interventions was found. CONCLUSIONS: This is the first systematic review and meta-analysis that has examined the clinical and cost-effectiveness of physiotherapy interventions following TKR. The findings of this review suggest that physiotherapy interventions were effective for improving physical function, ROM and pain in a short-term follow-up following TKR. Insufficient evidence exists to establish the benefit of physiotherapy in the long term for patient with TKR. Further study should examine the long-term effectiveness and cost-effectiveness of physiotherapy interventions.

Meta-analysis of small for gestational age births and disinfection byproduct exposures.

BACKGROUND: Some epidemiological studies show associations between disinfection byproducts (DBPs) and adverse developmental outcomes. OBJECTIVES: We undertook a meta-analysis of epidemiological studies on maternal exposure to trihalomethanes (THMs) and haloacetic acids (HAAs) and risk of small for gestational age (SGA) birth. METHODS: We identified forty-five publications including two reports and five theses via a 2020 literature search. Nineteen study populations from 16 publications met the inclusion criteria and were systematically evaluated. Effect measures were pooled using random effects meta-analytic methods along with cumulative, sub-group and meta-regression analyses to examine between-study heterogeneity and variation in risk across different DBP measures. RESULTS: We detected a small increased risk for SGA with exposure to the sum of four (i.e., THM4) THM4 (odds ratio (OR) = 1.07; 95%CI: 1.03, 1.11), chloroform (OR = 1.05; 95%CI: 1.01, 1.08), bromodichloromethane (OR = 1.08; 95%CI: 1.05, 1.11) and the sum of the brominated THM4 (OR = 1.05; 95%CI: 1.02, 1.09). Larger ORs were detected for the sum of five haloacetic acids (i.e., HAA5) (OR = 1.12; 95%CI: 1.01, 1.25), dichloroacetic acid (OR = 1.25; 95%CI: 1.01, 1.41) and trichloroacetic acid (OR = 1.21; 95%CI: 1.07, 1.37). We detected larger SGA risks for several THM4 among the prospective cohort and case-control studies compared to retrospective cohorts and for the SGA3/5% (vs. SGA10%) studies. The THM4 meta-regression showed associations between SGA and the total quality score based on categorical or continuous measures. For example, an OR of 1.03 (95%CI: 1.01, 1.06) was detected for each 10-point increase in the study quality score based on our systematic review. CONCLUSIONS: We detected a small increased risk of SGA based on 18 THM4 study populations that was comparable to a previous meta-analysis of eight THM4 study populations. We also found increased risks for other THM4 and HAA measures not previously examined; these results were robust after accounting for outliers, publication bias, type of SGA classification, different exposure windows, and other factors.

Cost-effectiveness of physiotherapeutic interventions for low back pain: a systematic review.

BACKGROUND: Due to the rapid increase in healthcare costs of low back pain (LBP), it is important to provide clinically effective and cost-effective interventions to individuals with the condition. OBJECTIVE: To evaluate all recent economic evaluations of physiotherapeutic interventions for patients with LBP. DATA SOURCES: A literature search of Cumulative Index to Nursing and Allied Health Literature, MEDLINE, the National Health Service Economic Evaluation Database, Health Technology Assessment and Database of Abstracts of Review of Effects (January 2008 to October 2018) was undertaken. STUDY SELECTION: Randomised controlled trials and cohort studies that assessed the cost- effectiveness of physiotherapeutic interventions on patients with LBP compared with a control group were included in this review. A Consolidated Health Economic Evaluation Reporting Standards checklist was used to assess the quality of studies. DATA EXTRACTION/DATA SYNTHESIS: Two authors extracted data independently. A descriptive synthesis was conducted to summarise the data. RESULTS: In total, 1531 articles were identified and 11 studies met the inclusion criteria for this review. The total number of study participants in this review was 2633 and their ages ranged from 18 to 80 years. The duration of LBP in these patients ranged from 3 weeks to 1 year. Excluding one study, all studies reported that the physiotherapeutic intervention was cost-effective compared with the control arm. Meta-analysis was not possible due to heterogeneity of the studies. CONCLUSION: Although most studies in this review suggested that physiotherapeutic interventions were cost-effective, it is difficult to pool their results for conclusive evidence. Systematic review registration number CRD: 42018089773.

Clinical and cost-effectiveness of physiotherapy interventions following total hip replacement: a systematic review and meta-analysis.

To examine the reported clinical and cost-effectiveness of physiotherapy interventions following total hip replacement (THR). A systematic review was completed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). MEDLINE, CINAHL, AMED, Scopus, DARE, HTA, and NHS EED databases were searched for studies on clinical and cost-effectiveness of physiotherapy in adults with THR published up to March 2020. Studies meeting the inclusion criteria were identified and key data were extracted. Risk of bias was assessed using the Cochrane Risk of Bias Tool and a Consolidated Health Economic Evaluation Reporting Standards (CHEERS). Data were summarised and combined using random-effect meta-analysis. A total of 1263 studies related to the aim of the review were identified, from which 20 studies met the inclusion criteria and were included in the review. These studies were conducted in Australia (n = 3), Brazil (n = 1), United States of America (USA) (n = 2), France (n = 2), Italy (n = 2), Germany (n = 3), Ireland (n = 1), Norway (n = 2), Canada (n = 1), Japan (n = 1), Denmark (n = 1), and United Kingdom (UK) (n = 1). The duration of follow-up of the included studies was ranged from 2 weeks to 12 months. Physiotherapy interventions were found to be clinically effective for functional performance, hip muscle strength, pain, and range of motion flexion. From the National Health Service perspective, an accelerated physiotherapy programme following THR was cost-effective. The findings of the review suggest that physiotherapy interventions were clinically effective for people with THR. However, questions remain on the pooled cost-effectiveness of physiotherapy interventions, and further research is required to examine this in patients with THR. Future studies are required to examine the cost-effectiveness of these interventions from patients, caregivers, and societal perspectives.Registration Prospero (ID: CRD42018096524).

'Warning: allergic to penicillin': association between penicillin allergy status in 2.3 million NHS general practice electronic health records, antibiotic prescribing and health outcomes.

BACKGROUND: The prevalence of reported penicillin allergy (PenA) and the impact these records have on health outcomes in the UK general population are unknown. Without such data, justifying and planning enhanced allergy services is challenging. OBJECTIVES: To determine: (i) prevalence of PenA records; (ii) patient characteristics associated with PenA records; and (iii) impact of PenA records on antibiotic prescribing/health outcomes in primary care. METHODS: We carried out cross-sectional/retrospective cohort studies using patient-level data from electronic health records. Cohort study: exact matching across confounders identified as affecting PenA records. Setting: English NHS general practices between 1 April 2013 and 31 March 2014. Participants: 2.3 million adult patients. Outcome measures: prevalence of PenA, antibiotic prescribing, mortality, MRSA infection/colonization and Clostridioides difficile infection. RESULTS: PenA prevalence was 5.9% (IQR = 3.8%-8.2%). PenA records were more common in older people, females and those with a comorbidity, and were affected by GP practice. Antibiotic prescribing varied significantly: penicillins were prescribed less frequently in those with a PenA record [relative risk (RR)  = 0.15], and macrolides (RR = 4.03), tetracyclines (RR = 1.91) nitrofurantoin (RR = 1.09), trimethoprim (RR = 1.04), cephalosporins (RR = 2.05), quinolones (RR = 2.10), clindamycin (RR = 5.47) and total number of prescriptions were increased in patients with a PenA record. Risk of re-prescription of a new antibiotic class within 28 days (RR = 1.32), MRSA infection/colonization (RR = 1.90) and death during the year subsequent to 1 April 2013 (RR = 1.08) increased in those with PenA records. CONCLUSIONS: PenA records are common in the general population and associated with increased/altered antibiotic prescribing and worse health outcomes. We estimate that incorrect PenA records affect 2.7 million people in England. Establishing true PenA status (e.g. oral challenge testing) would allow more people to be prescribed first-line antibiotics, potentially improving health outcomes.

Randomized controlled feasibility trial of supported self-management in adults with Type 2 diabetes mellitus and an intellectual disability: OK Diabetes.

AIMS: To undertake a feasibility randomized controlled trial of supported self-management vs treatment as usual in a population of adults with obesity, Type 2 diabetes and an intellectual disability. METHODS: We conducted an individually randomized feasibility trial. Participants were adults aged >18 years with a mild or moderate intellectual disability, living in the community with Type 2 diabetes, on any therapy other than insulin. Participants had mental capacity to consent to research and the intervention. Inclusion criteria included HbA1c > 48 mmol/mol (6.5%), BMI >25 kg/m2 , or self-reported physical activity below national guideline levels. The experimental intervention was standardized supported self-management delivered by diabetes specialist nurses plus treatment as usual, compared with treatment as usual alone. Feasibility outcomes included: recruitment and retention; intervention acceptability and feasibility; data collection and completeness for physiological state and values for candidate primary outcomes (HbA1c and BMI). RESULTS: A total of 82 participants (89% of those contacted and eligible) were randomized. All supported self-management sessions were completed by 35/41 participants (85%); only four completed no sessions. Data on the follow-up candidate primary outcomes HbA1c and BMI were obtained for 75/82 (91%) and 77/82 participants (94%), respectively. The mean baseline HbA1c was 56±16.5 mmol/mol (7.3±1.5%) and the mean BMI was 34±7.6 kg/m2 . CONCLUSIONS: Adherence to supported self-management and willingness to have blood taken for outcome measurement was good. A definitive randomized controlled trial is feasible in this population. (Trial registration: Current Controlled Trials ISRCTN41897033).

Optimizing the Bioavailability of Subcutaneously Administered Biotherapeutics Through Mechanochemical Drivers.

The subcutaneous route offers myriad benefits for the administration of biotherapeutics in both acute and chronic diseases, including convenience, cost effectiveness and the potential for automation through closed-loop systems. Recent advances in parenteral administration devices and the use of additives which enhance drug dispersion have generated substantial additional interest in IV to SQ switching studies. Designing pre-clinical and clinical studies using SQ mediated delivery however requires deep understanding of complex inter-related physiologies and transport pathways governing the interstitial matrix, vascular system and lymphatic channels. This expert review will highlight key structural features which contribute to transport and biodistribution in the subcutaneous space and also assess the impact of drug formulations. Based on the rapidly growing interest in the SQ delivery route, a number of potential areas for future development are highlighted, which are likely to allow continued evolution and innovation in this important area.

The ethical issues regarding consent to clinical trials with pre-term or sick neonates: a systematic review (framework synthesis) of the empirical research.

BACKGROUND: Conducting clinical trials with pre-term or sick infants is important if care for this population is to be underpinned by sound evidence. Yet approaching parents at this difficult time raises challenges for the obtaining of valid informed consent to such research. This study asked: what light does the empirical literature cast on an ethically defensible approach to the obtaining of informed consent in perinatal clinical trials? METHODS: A systematic search identified 49 studies. Analysis began by applying philosophical frameworks which were then refined in light of the concepts emerging from empirical studies to present a coherent picture of a broad literature. RESULTS: Between them, studies addressed the attitudes of both parents and clinicians concerning consent in neonatal trials; the validity of the consent process in the neonatal research context; and different possible methods of obtaining consent. CONCLUSIONS: Despite a variety of opinions among parents and clinicians there is a strongly and widely held view that it is important that parents do give or decline consent for neonatal participation in trials. However, none of the range of existing consent processes reviewed by the research is satisfactory. A significant gap is evaluation of the widespread practice of emergency 'assent', in which parents assent or refuse their baby's participation as best they can during the emergency and later give full consent to ongoing participation and follow-up. Emergency assent has not been evaluated for its acceptability, how such a process would deal with bad outcomes such as neonatal death between assent and consent, or the extent to which late parental refusal might bias results. This review of a large number of empirical papers, while not making fundamental changes, has refined and developed the conceptual framework from philosophy for examining informed consent in this context.

Close collaboration between local and specialist multidisciplinary teams allows 'fast-tracking' of patients with colorectal liver metastases.

AIM: The ongoing evolution of treatment strategies for colorectal liver metastases necessarily requires all patients to be reviewed at some point by the specialist hepatobiliary unit. This process can be streamlined through close collaboration with the local colorectal multidisciplinary team (MDT). The study was performed to see if a local colorectal MDT was able to make a correct decision regarding potential operability of liver metastases, by comparing its decision with that of two hepatobiliary surgeons in our referral centre. METHOD: CT scans of 38 patients found to have liver metastases from colorectal cancer were anonymized and sent to two hepatobiliary surgeons in our cancer network. They classified them into three categories: R, resectable; C, chemotherapy to downsize then consider resection; U, unresectable. The results were then compared with the opinion of our colorectal MDT, made before the referral to the hepatobiliary surgeons. RESULTS: The two independent hepatobiliary surgeons agreed with each other on 35/38 (92%) of CT scans. Our colorectal MDT agreed with the hepatobiliary surgeons in 36/38 (95%) of cases. Only 9 (32%) of the 28 patients deemed suitable on the CT scan by the hepatobiliary surgeons actually had a liver resection. CONCLUSION: The results show that a local colorectal MDT is able to make an accurate assessment of the operability of liver metastases. Patients deemed to be inoperable by the colorectal MDT could be 'fast-tracked' to the hepatobiliary MDT with review of imaging only, saving time and resources by avoiding referral of patients who are not suitable for liver resection.

CD14, a key candidate gene associated with a specific immune response to cockroach.

BACKGROUND: Sensitization to cockroach allergen is one of the strongest predictors of asthma morbidity, especially among African Americans. OBJECTIVE: Our aims were to determine the genomic basis of cockroach sensitization and the specific response to cockroach antigen. METHODS: We investigated the Th1/Th2 cytokine profile of co-cultured plasmacytoid dendritic cells (pDCs) and CD4+ T cells and the 'transcript signature' of the immune response to cockroach antigen using high-throughput expression profiling of co-cultured cells. RESULTS: We observed significantly elevated levels of IL-13, IL-10, and TNF-alpha, but undetectable levels of IL-12p70 and IFN-alpha, when cultures were exposed to crude cockroach antigen. A significant difference was observed for IL-13 between cockroach-allergic and non-allergic individuals (P=0.039). Microarray analyses demonstrated a greater response at 48 h compared with 4 h, with 50 genes being uniquely expressed in cockroach antigen-treated cells, including CD14, S100A8, CCL8, and IFI44L. The increased CD14 expression was further observed in purified pDCs, human monocytic THP-1 cells, and the supernatant of co-cultured pDCs and CD4+ T cells on exposure to cockroach extract. Furthermore, the most differential expression of CD14 between cockroach allergy and non-cockroach allergy was only observed among individuals with the CC 'high-risk' genotype of the CD14-260C/T. Ingenuity Pathways Analysis analyses suggested the IFN signalling as the most significant canonical pathway. CONCLUSION: Our results suggest that these differentially expressed genes, particularly CD14, and genes in the IFN signalling pathway may be important candidates for further investigation of their role in the immune response to cockroach allergen.

The impact of agglomeration and storage on flavor and flavor stability of whey protein concentrate 80% and whey protein isolate.

The impact of agglomeration on flavor and flavor stability of whey protein concentrates 80% (WPC80) and whey protein isolates (WPI) has not been widely addressed. This study examined the impact of agglomeration on the flavor and flavor stability of commercial WPC80 and WPI across 18 mo of storage. Duplicate agglomerated and nonagglomerated WPC80 and WPI were collected from 4 facilities and stored at 21 degrees C, 50% relative humidity. Volatile analysis using solid phase microextraction (SPME) with gas chromatography-mass spectrometry (GC-MS) and descriptive sensory analysis were conducted every 2 mo. Solubility index, bulk volume, dispersibility, moisture, and color (L, a, b) were tested every 3 or 6 mo. Consumer acceptance testing with protein beverages was conducted with fresh and stored whey proteins. Higher intensities and more rapid development of lipid oxidation flavors (cardboard, raisin/brothy, cucumber, and fatty) were noted in agglomerated powders compared to nonagglomerated powders (P < 0.05). Volatile analysis results confirmed sensory results, which indicated increased formation of aldehydes and ketones in agglomerated products compared to nonagglomerated powders (P < 0.05). Consumer acceptance scores for protein beverages were lower for beverages made with agglomerated WPC80 stored for 12 mo and agglomerated or nonagglomerated WPI stored for 18 mo compared to fresh products while trained panelists detected differences among beverages and rehydrated proteins earlier. Agglomeration with or without lecithin decreased the storage stability of whey proteins. These results indicate that the optimum shelf life at 21 degrees C for nonagglomerated whey proteins is 12 to 15 mo and 8 to 12 mo for agglomerated whey proteins.

Blood pressure lowering efficacy of renin inhibitors for primary hypertension: a Cochrane systematic review.

We conducted a systematic review and meta-analysis of double-blind randomized controlled trials to quantify the dose-related systolic (SBP) and diastolic blood pressure (DBP) lowering efficacy of renin inhibitors vs placebo in the treatment of adults with primary hypertension. Databases searched were Medline (1966-March 2008), EMBASE (1988-March 2008) and Cochrane Central Register of Controlled Trials (CENTRAL). Six trials in 3694 patients met the inclusion criteria. All examined aliskiren, the only renin inhibitor licensed for marketing in Canada and the United States. Aliskiren caused a dose-related SBP/DBP lowering effect compared to placebo: weighted mean difference with 95% CI: aliskiren 75 mg, -2.9 (-4.6, -1.3)/-2.3 (-3.3, -1.3) mm Hg; aliskiren 150 mg, -5.5 (-6.5, -4.4)/-3.0 (-3.7, -2.3) mm Hg; aliskiren 300 mg, -8.7 (-9.7,-7.6)/-5.0 (-5.6, -4.3) and aliskiren 600 mg, -11.4 (-13.5, -9.2)/-6.6 (-7.9, -5.2) mm Hg. Aliskiren 300 mg significantly lowered both SBP -3.0 (-4.0, -2.0) and DBP -1.7 (-2.3, -1.0) as compared to aliskiren 150 mg. Aliskiren has no effect on blood pressure variability. No data were available to assess the effect of aliskiren on heart rate or pulse pressure. This review found weak evidence that during 4- to 8-week use, aliskiren did not increase withdrawals due to adverse effects as compared to placebo. We concluded that aliskiren has a dose-related blood pressure lowering effect better than placebo and magnitude of effect is similar to that determined for angiotensin-converting enzyme inhibitors and angiotensin receptor blockers.

Coexistence of Sjögren's syndrome and sarcoidosis: a report of five cases.

BACKGROUND: Sjögren's syndrome (SS) and sarcoidosis are diseases that can affect the salivary glands and result in the loss of salivary gland function. Most of the criteria used for the diagnosis of SS exclude sarcoidosis before establishing the diagnosis of SS. However, several reports have suggested the coexistence of both SS and sarcoidosis in the same patient. OBJECTIVE: The purpose of this study was to present five cases that support a true coexistence of sarcoidosis and SS. METHODS: Clinical and laboratory findings of patients with evidence of having both SS and sarcoidosis were reviewed. The diagnosis of SS was based on the European community criteria; the diagnosis of sarcoidosis was based on the presence of serological, radiographic and/or histopathologic findings that are consistent with sarcoidosis. RESULTS: All patients fulfilled the criteria for the diagnosis of both diseases. CONCLUSION: Our findings appear to support a true coexistence of sarcoidosis with SS. Therefore, it is reasonable to suggest removing the exclusion of sarcoidosis from the diagnostic criteria for SS.

Effect of trihalomethane exposure on fetal development.

AIMS: To examine the effect of trimester specific and pregnancy average total trihalomethane (TTHM) exposure on infant birth weight, low birth weight, and intrauterine growth retardation in term births, as well as gestational age and preterm delivery in all births. METHODS: Cross sectional analysis of 56 513 singleton infants born to residents of Massachusetts during 1990. City specific aggregate data were used to estimate maternal exposure to TTHM concentration; individual maternal information was used to adjust for confounding. RESULTS: Increased pregnancy average and second trimester TTHM exposure were associated with small for gestational age and reductions in birth weight after adjusting for potential confounding variables. Compared to

Dynamics of 5S rDNA in the tilapia (Oreochromis niloticus) genome: repeat units, inverted sequences, pseudogenes and chromosome loci.

In higher eukaryotes, the 5S ribosomal DNA (5S rDNA) is organized in tandem arrays with repeat units composed of a coding region and a non-transcribed spacer sequence (NTS). These tandem arrays can be found on either one or more chromosome pairs. 5S rDNA copies from the tilapia fish, Oreochromis niloticus, were cloned and the nucleotide sequences of the coding region and of the non-transcribed spacer were determined. Moreover, the genomic organization of the 5S rDNA tandem repeats was investigated by fluorescence IN SITU hybridization (FISH) and Southern blot hybridization. Two 5S rDNA classes, one consisting of 1.4-kb repeats and another one with 0.5-kb repeats were identified and designated 5S rDNA type I and type II, respectively. An inverted 5S rRNA gene and a 5S rRNA putative pseudogene were also identified inside the tandem repeats of 5S rDNA type I. FISH permitted the visualization of the 5S rRNA genes at three chromosome loci, one of them consisting of arrays of the 5S rDNA type I, and the two others corresponding to arrays of the 5S rDNA type II. The two classes of the 5S rDNA, the presence of pseudogenes, and the inverted genes observed in the O. niloticus genome might be a consequence of the intense dynamics of the evolution of these tandem repeat elements.

Biologically active sequence (KDI) mediates the neurite outgrowth function of the gamma-1 chain of laminin-1.

A neurite outgrowth domain of the gamma1-chain of laminin-1 (RDIAEIIKDI) promotes axon guidance of rat hippocampal neurons, regulates the nuclear movement phase of neuronal migration, and binds to the cellular prion protein (Liesi et al. [1995] J. Neurosci. Res. 134:447-486; Matsuzawa et al. [1998] J. Neurosci. Res. 53:114-124; Graner et al. [2000] Brain Res. Mol. Brain Res. 76:85-92). Using electrophysiology and neuronal culture experiments, we show that this 10 amino acid peptide or its smaller domains induces potassium currents in primary central neurons. Both these currents and the neurotoxicity of high concentrations of the 10 amino acid peptide antigen are prevented by pertussis toxin. The smallest peptide domain capable of inducing both potassium currents and promoting neurite outgrowth of human spinal cord neurons is a tri-peptide KDI. Our results indicate that KDI may be the biologically active domain of the gamma1 laminin, capable of modulating electrical activity and survival of central neurons via a G-protein coupled mechanism. These results expand the wide variety of functions already reported for the members of the laminin-gene family. They suggest that biologically active peptide domains of the gamma1 laminin may provide tools to promote neuronal regeneration after injuries and to enhance neuronal survival during aging and neuronal degeneration.