Intravitreal aflibercept 8 mg in neovascular age-related macular degeneration (PULSAR): 48-week results from a randomised, double-masked, non-inferiority, phase 3 trial.

BACKGROUND: Intravitreal aflibercept 8 mg could improve treatment outcomes and provide sustained disease control in patients with neovascular age-related macular degeneration (nAMD), with extended dosing compared with aflibercept 2 mg. METHODS: PULSAR is a phase 3, randomised, three-group, double-masked, non-inferiority, 96-week trial conducted across 223 sites worldwide. Adults with nAMD were randomised 1:1:1 to aflibercept 8 mg every 12 weeks (8q12), aflibercept 8 mg every 16 weeks (8q16), or aflibercept 2 mg every 8 weeks (2q8), following three initial monthly doses in all groups. From week 16, patients in the aflibercept 8 mg groups had their dosing interval shortened if pre-specified dose regimen modification criteria denoting disease activity were met. The primary endpoint was change from baseline in best-corrected visual acuity (BCVA) at week 48. All patients with at least one dose of study treatment were included in the efficacy and safety analyses. This trial is registered with ClinicalTrials.gov (NCT04423718) and is ongoing. FINDINGS: Of 1011 patients randomised to aflibercept 8q12 (n=336), 8q16 (n=338), or 2q8 (n=337) between Aug 11, 2020, and July 30, 2021, 1009 patients received study treatment (aflibercept 8q12 n=335; aflibercept 8q16 n=338; and aflibercept 2q8 n=336). Aflibercept 8q12 and 8q16 showed non-inferior BCVA gains versus aflibercept 2q8 (mean BCVA change from baseline +6·7 [SD 12·6] and +6·2 [11·7] vs +7·6 [12·2] letters). The least squares mean differences between aflibercept 8q12 versus 2q8 and 8q16 versus 2q8, respectively, were -0·97 (95% CI -2·87 to 0·92) and -1·14 (-2·97 to 0·69) letters (non-inferiority margin at 4 letters). The incidence of ocular adverse events in the study eye was similar across groups (aflibercept 8q12 n=129 [39%]; aflibercept 8q16 n=127 [38%]; and aflibercept 2q8 n=130 [39%]). INTERPRETATION: Aflibercept 8 mg showed efficacy and safety with extended dosing intervals, which has the potential to improve the management of patients with nAMD. FUNDING: Bayer AG and Regeneron Pharmaceuticals.

Intravitreal aflibercept 8 mg in diabetic macular oedema (PHOTON): 48-week results from a randomised, double-masked, non-inferiority, phase 2/3 trial.

BACKGROUND: A high-dose formulation of intravitreal aflibercept (8 mg) could improve treatment outcomes in diabetic macular oedema (DMO) by requiring fewer injections than the standard comparator, aflibercept 2 mg. We report efficacy and safety results of aflibercept 8 mg versus 2 mg in patients with DMO. METHODS: PHOTON was a randomised, double-masked, non-inferiority, phase 2/3 trial performed at 138 hospitals and specialty retina clinics in seven countries. Eligible patients were adults aged 18 years or older with type 1 or 2 diabetes and centre-involved DMO. Patients were randomly assigned (1:2:1) to intravitreal aflibercept 2 mg every 8 weeks (2q8), aflibercept 8 mg every 12 weeks (8q12), or aflibercept 8 mg every 16 weeks (8q16), following initial monthly dosing. From week 16, dosing intervals for the aflibercept 8 mg groups were shortened if patients met prespecified dose regimen modification criteria denoting disease activity. The primary endpoint was change from baseline in best-corrected visual acuity (BCVA) at week 48 (non-inferiority margin of 4 letters). Efficacy and safety analyses included all randomly assigned patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov (NCT04429503). FINDINGS: Between June 29, 2020, and June 28, 2021, 970 patients were screened for eligibility. After exclusions, 660 patients were enrolled and randomly assigned to receive aflibercept 8q12 (n=329), 8q16 (n=164), or 2q8 (n=167); two patients were randomly assigned in error and did not receive treatment. 658 (99·7%) patients were treated and included in the full analysis set and safety analysis set (8q12 n=328, 8q16 n=163, and 2q8 n=167). Mean patient age was 62·3 years (SD 10·4). 401 (61%) patients were male. 471 (72%) patients were White. Aflibercept 8q12 and 8q16 demonstrated non-inferior BCVA gains to aflibercept 2q8 (BCVA mean change from baseline 8·8 letters [SD 9·0] in the 8q12 group, 7·9 letters [8·4] in the 8q16 group, and 9·2 letters [9·0] in the 2q8 group). The difference in least squares means was -0·57 letters (95% CI -2·26 to 1·13, p value for non-inferiority <0·0001) between 8q12 and 2q8 and -1·44 letters (-3·27 to 0·39, p value for non-inferiority 0·0031) between aflibercept 8q16 and 2q8. Proportions of patients with ocular adverse events in the study eye were similar across groups (8q12 n=104 [32%], 8q16 n=48 [29%], and 2q8 n=46 [28%]). INTERPRETATION: Aflibercept 8 mg demonstrated efficacy and safety with extended dosing intervals and could decrease treatment burden in patients with DMO. FUNDING: Regeneron Pharmaceuticals and Bayer.

Contraceptive efficacy and safety of the 52-mg levonorgestrel intrauterine system for up to 8 years: findings from the Mirena Extension Trial.

BACKGROUND: The 52-mg levonorgestrel-releasing intrauterine system is an established, long-acting contraceptive option with approved use for up to 7 years. OBJECTIVE: The Mirena Extension Trial evaluated the efficacy and safety of the 52-mg levonorgestrel-releasing intrauterine system during extended use beyond 5 and up to 8 years. STUDY DESIGN: This was a multicenter, single-arm study in the United States, enrolling existing users of the 52-mg levonorgestrel-releasing intrauterine system, aged 18 to 35 years, who have had the system for 4.5 to 5 years. We assessed the contraceptive efficacy (Pearl Index) and cumulative failure rate (using the Kaplan-Meier method) of the 52-mg levonorgestrel-releasing intrauterine system during extended use. We also evaluated bleeding outcomes and adverse events. RESULTS: Of the 362 participants starting year 6, 243 entered and 223 completed 8 years of 52-mg levonorgestrel-releasing intrauterine system use. Just more than half the participants were parous. The mean (standard deviation) age was 29.2 (±2.9) years, and all participants were aged ≤36 years at the end of year 8. Two pregnancies occurred, both with the device in situ. The year 6 pregnancy was of undetermined location and resolved spontaneously. The pregnancy in year 7 was ectopic and resolved with methotrexate treatment. In both cases, the 52-mg levonorgestrel-releasing intrauterine system was removed and the participants left the trial. For years 6 to 8, the 3-year Pearl Index (95% confidence interval) was 0.28 (0.03-1.00) with a 3-year cumulative failure rate of 0.68% (0.17-2.71). Pearl Indexes for years 6, 7, and 8 were 0.34 (0.01-1.88), 0.40 (0.01-2.25), and 0.00 (0.00-1.90), respectively. The 3-year (years 6-8) ectopic pregnancy Pearl Index was 0.14 (0.00-0.77). We found treatment-emergent adverse events in 249 of 362 participants (68.8%), with 65 (18.0%) events considered to be related to the 52-mg levonorgestrel-releasing intrauterine system. The discontinuation rate was 38.4% (139/362), most commonly because of desire for pregnancy (12.2%, 44/362). During extended use beyond 5 years and up to 8 years, participants reported a decrease in the mean number of bleeding or spotting days with approximately half of the women experiencing amenorrhea or infrequent bleeding. We did not enroll a sufficient number of women using the 52-mg levonorgestrel-releasing intrauterine system for contraception and heavy menstrual bleeding to assess extended use for that indication. At the end of year 8, most (98.7%, 220/223) of the participants who completed the study remained satisfied with the continued use of the 52-mg levonorgestrel-releasing intrauterine system. Of the 31 women who discontinued early because of desire for pregnancy with evaluable data for return-to-fertility analysis, 24 reported a posttreatment pregnancy within 1 year, giving a 12-month return-to-fertility rate of 77.4%. CONCLUSION: The 52-mg levonorgestrel-releasing intrauterine system, initially approved for 5 years, maintains high contraceptive efficacy, user satisfaction, and a favorable safety profile through 8 years of use. Participants reported 26 posttreatment pregnancies in total, of which 24 occurred in women who had discontinued the 52-mg levonorgestrel-releasing intrauterine system because of a desire for pregnancy. Of note, among women who elected to continue use through 8 years, bleeding patterns remained highly favorable. These findings support continued 52-mg levonorgestrel-releasing intrauterine system use for up to 8 years in women who wish to continue treatment.

Impact of COVID-19 crisis on medical care of patients with metastasized uro-oncologic disease under systemic cancer therapy: a multicenter study in German university hospitals.

PURPOSE: To date, over 4.2 million Germans and over 235 million people worldwide have been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Uro-oncology (UO) patients are particularly vulnerable but in urgent need of life-saving systemic treatments. Our multicentric study examined the impact of the COVID-19 crisis on the medical care of UO patients in German university hospitals receiving ongoing systemic anti-cancer treatment and to detect the delay of medical care, defined as deferred medical treatment or deviation of the pre-defined follow-up assessment. METHODS: Data of 162 UO patients with metastatic disease undergoing systemic cancer treatment at five university hospitals in Germany were included in our analyses. The focus of interest was any delay or change in treatment between February 2020 and May 2020 (first wave of the COVID-19 crisis in Germany). Statistical analysis of contingency tables were performed using Pearson's chi-squared and Fisher's exact tests, respectively. Effect size was determined using Cramér's V (V). RESULTS: Twenty-four of the 162 patients (14.8%) experienced a delay in systemic treatment of more than 2 weeks. Most of these received immuno-oncologic (IO) treatments (13/24, 54.2%, p = 0.746). Blood tests were delayed or canceled significantly more often in IO patients but with a small effect size (21.1%, p = 0.042, V = 0.230). Treatment of patients with renal cell carcinoma (12/73, 16.4%) and urothelial carcinoma (7/32, 21.9%) was affected the most. CONCLUSIONS: Our data show that the COVID-19 pandemic impacted the medical care of UO patients, but deferment remained modest. There was a tendency towards delays in IO and ADT treatments in particular.

Two-colour single-molecule photoinduced electron transfer fluorescence imaging microscopy of chaperone dynamics.

Many proteins are molecular machines, whose function is dependent on multiple conformational changes that are initiated and tightly controlled through biochemical stimuli. Their mechanistic understanding calls for spectroscopy that can probe simultaneously such structural coordinates. Here we present two-colour fluorescence microscopy in combination with photoinduced electron transfer (PET) probes as a method that simultaneously detects two structural coordinates in single protein molecules, one colour per coordinate. This contrasts with the commonly applied resonance energy transfer (FRET) technique that requires two colours per coordinate. We demonstrate the technique by directly and simultaneously observing three critical structural changes within the Hsp90 molecular chaperone machinery. Our results reveal synchronicity of conformational motions at remote sites during ATPase-driven closure of the Hsp90 molecular clamp, providing evidence for a cooperativity mechanism in the chaperone's catalytic cycle. Single-molecule PET fluorescence microscopy opens up avenues in the multi-dimensional exploration of protein dynamics and allosteric mechanisms.

Insertion experience of women and health care professionals in the Kyleena® Satisfaction Study.

Purpose: The Kyleena® Satisfaction Study (KYSS) is a prospective, observational study conducted to assess satisfaction with LNG-IUS 12 (Kyleena®) in clinical practice and aims to provide adequate information for counselling women on what to expect regarding insertion and satisfaction.Materials and methods: Women deciding to use LNG-IUS 12 during routine counselling were informed of the study and provided informed consent. A baseline analysis was conducted to evaluate demographics, ease of insertion assessed by investigators, pain at insertion rated by women, additional interventions for insertion, and adverse events.Results: 1,110 women (536 parous, 574 nulliparous) had an insertion attempt and were included. Insertion was rated as easy in 494 (92.2%) parous and 516 (89.9%) nulliparous women. Pain was assessed as none or mild by 475 (88.6%) parous and 387 (67.4%) nulliparous women. Additional interventions were not required for most insertions (705; 63.6%). Overall 111 (10.0%) women reported adverse events at the time of baseline analysis.Conclusions: This analysis demonstrates that LNG-IUS 12 insertion is easy and associated with no or mild pain in most women. Additional interventions for insertion are not required in most cases. After 3 months, the number of adverse events is low.Implications: The present baseline analysis of the Kyleena® Satisfaction Study (KYSS) demonstrates that most women rate insertion pain of LNG-IUS 12 as none or mild and clinicians consider insertion easy in the majority of cases.

The 11-year long-term follow-up study from the randomized BENEFIT CIS trial.

OBJECTIVE: To assess outcomes for patients treated with interferon beta-1b immediately after clinically isolated syndrome (CIS) or after a short delay. METHODS: Participants in BENEFIT (Betaferon/Betaseron in Newly Emerging MS for Initial Treatment) were randomly assigned to receive interferon beta-1b (early treatment) or placebo (delayed treatment). After conversion to clinically definite multiple sclerosis (CDMS) or 2 years, patients on placebo could switch to interferon beta-1b or another treatment. Eleven years after randomization, patients were reassessed. RESULTS: Two hundred seventy-eight (59.4%) of the original 468 patients (71.3% of those eligible at participating sites) were enrolled (early: 167 [57.2%]; delayed: 111 [63.1%]). After 11 years, risk of CDMS remained lower in the early-treatment arm compared with the delayed-treatment arm (p = 0.0012), with longer time to first relapse (median [Q1, Q3] days: 1,888 [540, not reached] vs 931 [253, 3,296]; p = 0.0005) and lower overall annualized relapse rate (0.21 vs 0.26; p = 0.0018). Only 25 patients (5.9%, overall; early, 4.5%; delayed, 8.3%) converted to secondary progressive multiple sclerosis. Expanded Disability Status Scale scores remained low and stable, with no difference between treatment arms (median [Q1, Q3]: 2.0 [1.0, 3.0]). The early-treatment group had better Paced Auditory Serial Addition Task-3 total scores (p = 0.0070). Employment rates remained high, and health resource utilization tended to be low in both groups. MRI metrics did not differ between groups. CONCLUSIONS: Although the delay in treatment was relatively short, several clinical outcomes favored earlier treatment. Along with low rates of disability and disease progression in both groups, this supports the value of treatment at CIS. CLINICALTRIALSGOV IDENTIFIER: NCT01795872. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that early compared to delayed treatment prolongs time to CDMS in CIS after 11 years.

Cooperation of local motions in the Hsp90 molecular chaperone ATPase mechanism.

The Hsp90 chaperone is a central node of protein homeostasis, activating many diverse client proteins. Hsp90 functions as a molecular clamp that closes and opens in response to the binding and hydrolysis of ATP. Crystallographic studies have defined distinct conformational states of the mechanistic core, implying structural changes that have not yet been observed in solution. Here we engineered one-nanometer fluorescence probes based on photoinduced electron transfer into the yeast Hsp90 to observe these motions. We found that the ATPase activity of the chaperone was reflected in the kinetics of specific structural rearrangements at remote positions that acted cooperatively. Nanosecond single-molecule fluorescence fluctuation analysis uncovered that critical structural elements that undergo rearrangement were mobile on a sub-millisecond time scale. We identified a two-step mechanism for lid closure over the nucleotide-binding pocket. The activating co-chaperone Aha1 mobilized the lid of apo Hsp90, suggesting an early role in the catalytic cycle.

Complete nucleotide sequence and evolutionary analysis of a gorilla foamy virus.

To shed light on primate foamy virus (FV) evolution, we determined the complete nucleotide sequence of the gorilla simian foamy virus (SFVgor). Starting from a conserved region in the integrase (IN) domain of the pol gene we cloned the viral genome to the 5' and 3' LTR into plasmid vectors and elucidated its nucleotide sequence. The sequences of both LTRs were determined by nucleotide sequencing of separate PCR products from the primer-binding site or the bel region and LTRs. All protein motifs conserved among the primate FV were identified in SFVgor. Using phylogenetic analysis of the Gag, Pol and Env amino acid sequences, we demonstrate that SFVgor consistently clusters in accordance with a scenario of virus-host co-divergence.

Ubiquitin domain proteins in disease.

The human genome encodes several ubiquitin-like (UBL) domain proteins (UDPs). Members of this protein family are involved in a variety of cellular functions and many are connected to the ubiquitin proteasome system, an essential pathway for protein degradation in eukaryotic cells. Despite their structural similarity, the UBL domains appear to have a range of different targets, resulting in a considerable diversity with respect to UDP function. Here, we give a short summary of the biochemical and physiological roles of the UDPs, which have been linked to human diseases including neurodegeneration and cancer. Publication history: Republished from Current BioData's Targeted Proteins database (TPdb; http://www.targetedproteinsdb.com).

Nasalance in patients with maxillary defects - Reconstruction versus obturation.

BACKGROUND: An important question remains on how to obtain good quality of speech for patients needing maxillectomy. Oral and nasal spaces must be separated either by surgical means or by using an obturator-prosthesis. An objective measure of oronasal closure is nasalance. Different rehabilitative strategies should be compared. METHODS: Between 1990 and 2000, 88 patients underwent maxillectomy of which 28 (32%) were available for examination. Ten patients had obturators (group l) and in 18 patients the maxilla was biologically reconstructed with different techniques (group 2). Sound pressure of nasal and oral airways were assessed seperately using a computerized sampling system (NasalView) and standardized German texts. Nasalance was calculated and compared with an uncompromised sample of patients. RESULTS: There were no significant differences between group 1 and group 2 concerning nasalance. Furthermore, the achieved values of nasalance were similar to healthy individuals. CONCLUSION: Nasalance after maxillectomy can be normal after sufficient rehabilitation.

The ubiquitin-domain protein HERP forms a complex with components of the endoplasmic reticulum associated degradation pathway.

To eliminate misfolded proteins that accumulate in the endoplasmic reticulum (ER) the cell mainly relies on ubiquitin-proteasome dependent ER-associated protein degradation (ERAD). Proteolysis of ERAD substrates by the proteasome requires their ubiquitylation and retro-translocation from the ER to the cytoplasm. Here we describe a high molecular mass protein complex associated with the ER membrane, which facilitates ERAD. It contains the ubiquitin domain protein (UDP) HERP, the ubiquitin protein ligase HRD1, as well as the retro-translocation factors p97, Derlin-1 and VIMP. Our data on the structural arrangement of these ERAD proteins suggest that p97 interacts directly with membrane-resident components of the complex including Derlin-1 and HRD1, while HERP binds directly to HRD1. We propose that ubiquitylation, as well as retro-translocation of proteins from the ER are performed by this modular protein complex, which permits the close coordination of these consecutive steps within ERAD.

Perioperative complications following sagittal split osteotomy of the mandible.

INTRODUCTION: The aim of this study was to review complications in a series of 1264 consecutive patients who were operated in a single centre during a 20-year-period. MATERIAL AND METHODS: Complications were documented, their incidences calculated and compared with data from the literature. RESULTS: In 35 patients (2.8%) infection developed requiring extraoral incision and drainage; in 27 patients (2.1%) the inferior alveolar nerve was inadvertently cut; 18 patients (1.4%) had to undergo re-operation due to bending or fracture of osteosynthesis material; 15 patients (1.2%) suffered from bleeding complications; in 12 patients (0.9%) an unfavourable split occurred. In 8 patients (0.6%) foreign bodies were left in situ; in 7 patients a partial weakness of the facial nerve occurred, which was permanent in 1 patient. Six patients (0.5%) with a significantly higher age than average (mean: 33.6 years in comparison with 23.1 years) developed non-union at the site of osteotomy, and the mandible had to be bone grafted. Two patients (0.2%) developed osteomyelitis, and in one patient airway problems led to a need for tracheostomy (0.1%). CONCLUSION: Although some of these complications of bilateral sagittal split with osteotomy carry severe limitations in health related quality of life, it remains an overall safe procedure, demanding, however, comprehensive informed consent. Good knowledge of technical reasons for these complications should help to reduce their incidence.

Intra- and perioperative complications of the LeFort I osteotomy: a prospective evaluation of 1000 patients.

The LeFort I osteotomy has become a routine procedure in elective orthognathic surgery. The authors report the occurrence of intra- or perioperative complications in a series of 1000 consecutive LeFort I osteotomies performed within a 20-year period. In total, 64 (6.4%) patients experienced complications. Anatomical complications affected 26 (2.6%), patients, including 16 (1.6%) with a deviation of the nasal septum and 10 (1.0%) with non-union of the osteotomy gap. Extensive bleeding that required blood transfusion occurred in 11 (1.1%) patients exclusively after bimaxillary corrections; in 1 patient a ligation of the external carotid artery became necessary. Significant infections such as abscesses or maxillary sinusitis occurred in 11 (1.1%) patients. No patient experienced an osteomyelitis. Ischemic complications affected 10 (1.0%) patients, including 2 (0.2%) who experienced an aseptic necrosis of the alveolar process and 8 (0.8%) who, under critical revision, were affected by retractions of the gingiva. Five (0.5%) patients experienced an insufficient fixation of the osteosynthesis material. The risk and the extent of complications was enhanced in patients with anatomical irregularities (eg, in patients with craniofacial dysplasias, orofacial clefts, or vascular anomalies). The risk of ischemic complications was enhanced in extensive dislocations or transversal segmentation of the maxilla. The authors conclude that patients with major anatomical irregularities should be informed about an enhanced risk of Le-Fort I osteotomies. Preoperative planning avoiding transversal segmentation or extensive dislocations of the maxilla should reduce the occurrence of complications. For healthy individuals, the risk of complications with the LeFort I osteotomy is considered low.

Coronin 7, the mammalian POD-1 homologue, localizes to the Golgi apparatus.

Coronins constitute an evolutionary conserved family of WD-repeat actin-binding proteins. Their primary function is thought to be regulating the actin cytoskeleton. Apart from that, several coronins were indirectly shown to participate in vesicular transport, establishment of cell polarity and cytokinesis. Here, we report a novel mammalian protein, coronin 7 (crn7), which is significantly different from other mammalian coronins in its domain architecture. Crn7 possesses two stretches of WD repeats in contrast to the other coronins only having one. The protein is expressed throughout the mouse embryogenesis and is strongly upregulated in brain and developing structures of the immune system in the course of development. In adult animals, both crn7 mRNA and protein are abundantly present in most organs, with significantly higher amounts in brain, kidney, thymus and spleen and lower amounts in muscle. At the subcellular level, the bulk of the protein appears to be present in the cytosol and in large cytosolic complexes. However, a significant portion of the protein is detected on vesicle-like cytoplasmic structures as well as on the cis-Golgi. In the Golgi region, crn7 staining appears broader than that of the cis-Golgi markers Erd2p and beta-COP, still, the trans-Golgi network appears predominantly crn7-negative. Importantly, the membrane-associated form of crn7 protein is phosphorylated on tyrosine residues, whereas the cytosolic form is not. Crn7 is the first coronin protein proven to localize to the Golgi membrane. We conclude that it plays a role in the organization of intracellular membrane compartments and vesicular trafficking rather than in remodeling the cytoskeleton.

Formation and emission of chloroanisoles as indoor pollutants.

GOAL, SCOPE AND BACKGROUND: Complaints by residents of frame-houses about musty odour in the houses has become an increasing problem within the last years. An additional problem is that the odour is transferred to clothes and skin. The persons themselves do not recognize the smell after a while because of adaptation. Serious social problems are the result. For a long time, the smell was explained to be from mould due to construction-based humidity problems. However, in an increasing number of houses, no indications were found for elevated levels of mould growth. METHODS: Air and material samples were taken from 5 houses, which show typical musty odours, and analysed with respect to chlorophenols and chloroanisoles. Additionally, some samples were analysed for lindane and its metabolites, because lindane was commonly used together with pentachlorophenol (PCP) for wood protection. RESULTS AND DISCUSSION: Meticulous analysis resulted in the identification of chloroanisoles, mainly 2,3,4,6-tetrachloroanisole. These substances are known from corky wines and from contamination of food from pentachlorophenol (PCP) treated pallets and result from microbiological metabolic processes. Pentachlorophenol was commonly used to protect wood from fungi in Germany mainly in the later 60s and 70s. Details of these processes, as well as effective methods to identify chloroanisoles in the problem houses, are described. CONCLUSIONS: Chloroanisoles formed by metabolism of PCP have been well known to contaminate food or wine. Here, they were identified and are probably responsible for the musty odours in the frame houses. Since it is quite clear that these substances were not components of building materials used in the houses, an explanation for chloroanisole formation is proposed. Localized dampness probably favours microbial growth associated with metabolic conversion of chlorophenols to the corresponding chloroanisoles, primarily 2,3,4,6-tetrachloroanisol, which spread throughout the buildings, resulting in the observed odours. RECOMMENDATIONS AND OUTLOOK: The group of chloroanisoles has been recognized as important indoor pollutants as they possess musty odours at extremely low concentrations, e.g. for 2,4,6-trichloroanisole in a range of 5-10 ppt in air (Staples 2000). On the basis of currently available toxicological data, exposure of the occupants to the concentrations of chloroanisoles measured is not associated with a health risk. No correlation could be observed between concentrations of chloroanisoles and PCP in house dust and indoor air. However, chloroanisoles are good indicators for possible PCP-treatment of wood in frame houses and their detection should initiate investigations on PCP contamination. Research is continuing to identify the microorganisms involved and to devise a remediation procedure for affected houses.

Estudio exploratorio sobre: conocimiento que poseen las embarazadas acerca de la importancia del control adecuado durante la gestación para prevenir alteraciones de implicancia fonoaudiológica en el niño / Exploration study about: knowledge that possess the pregnant about of the importance of the control adequate during the gestation for prevention alterations of implicance phonoaudiologic in the children

El trabajo abordó el tema de la importancia del control prenatal, el conocimiento de ciertos factores que pueden afectar al feto en desarrollo y el conocimiento acerca de la necesidad de recibir atención fonoaudiológica en trastornos del proceso comunicativo - ling³istico en los niños por complicaciones sufridas en el embarazo. Se investigó una población compuesta por 103 embarazadas con edades comprendidas entre 15 y 44 años de edad, que concurren a consulta médica en Consultorio Externo del Hospital Interzonal General de Agudos "San José", en la ciudad de ergamino, durante el período comprendido entre el 20 de agosto y el 22 de octubre del año 1998. Fue un trabajo de tipo exploratorio, de caracter transversal. La información se obtuvo a partir de una encuesta personal de 20 preguntas. Por medio de esta investigación se pudo concluir que el 75 por ciento de las embarazadas poseen conocimiento suficiente acerca de la importancia del control prenatal. El 73,8 por ciento posee conocimiento escaso acerca de algunos factores que pueden afectar al feto en desarrollo. El 42,7 por ciento afirman tener conocimiento acerca de la atención fonoaudiológica, de las cuales 19 embarazadas (43,2 por ciento) adquirieron formalmente esa información(AU)

Estudio exploratorio sobre: conocimiento que poseen las embarazadas acerca de la importancia del control adecuado durante la gestación para prevenir alteraciones de implicancia fonoaudiológica en el niño / Exploration study about: knowledge that possess the pregnant about of the importance of the control adequate during the gestation for prevention alterations of implicance phonoaudiologic in the children

El trabajo abordó el tema de la importancia del control prenatal, el conocimiento de ciertos factores que pueden afectar al feto en desarrollo y el conocimiento acerca de la necesidad de recibir atención fonoaudiológica en trastornos del proceso comunicativo - lingüistico en los niños por complicaciones sufridas en el embarazo. Se investigó una población compuesta por 103 embarazadas con edades comprendidas entre 15 y 44 años de edad, que concurren a consulta médica en Consultorio Externo del Hospital Interzonal General de Agudos "San José", en la ciudad de ergamino, durante el período comprendido entre el 20 de agosto y el 22 de octubre del año 1998. Fue un trabajo de tipo exploratorio, de caracter transversal. La información se obtuvo a partir de una encuesta personal de 20 preguntas. Por medio de esta investigación se pudo concluir que el 75 por ciento de las embarazadas poseen conocimiento suficiente acerca de la importancia del control prenatal. El 73,8 por ciento posee conocimiento escaso acerca de algunos factores que pueden afectar al feto en desarrollo. El 42,7 por ciento afirman tener conocimiento acerca de la atención fonoaudiológica, de las cuales 19 embarazadas (43,2 por ciento) adquirieron formalmente esa información