A robust H.264/AVC video watermarking scheme for copyright protection with self-adaptive drift compensation is proposed. In our scheme, motion vector residuals of macroblocks with the smallest partition size are selected to hide copyright information in order to hold visual impact and distortion drift to a minimum. Drift compensation is also implemented to reduce the influence of watermark to the most extent. Besides, discrete cosine transform (DCT) with energy compact property is applied to the motion vector residual group, which can ensure robustness against intentional attacks. According to the experimental results, this scheme gains excellent imperceptibility and low bit-rate increase. Malicious attacks with different quantization parameters (QPs) or motion estimation algorithms can be resisted efficiently, with 80% accuracy on average after lossy compression. With the rapid development of Internet and computer technology, digital multimedia industry meets huge opportunities as well as great challenges: copyright protection. Utilizing modern techniques, people can easily make the copied digital content identical to the original one. Digital watermarking technology is one of the most effective and efficient techniques to protect copyright under the open network circumstance. Since video products are mostly transmitted in compressed format, it is impossible to design a general watermark scheme applicable to different compression types. Thereby the compression standard must be considered in the design of video watermarking algorithm.The H.264/AVC standard is the latest video codec released by the Joint Video Team (JVT). As one of the most commonly used formats for the compression and distribution of high definition video, H.264/AVC introduces several new coding methods to improve the rate-distortion performance comparing with the past coding standards, such as MPEG-x and H.263.The earliest compressed domain watermarking scheme is based on Variable Length Coding (VLC) . HartungInsofar as evaluation criteria of watermark, imperceptibility is the basic principle, whereas the watermark embedding operation can easily import distortion drift, leading to a severe visual impact. Ma et al.  embeddedAnother important concern of watermark is the robustness against unintentional/intentional attacks. Langelaar and Lagendijk  proposedThe objective of this paper is to present a robust motion vector based watermarking method for H.264 video stream with drift compensation. DCT transform is adopted to motion vector residual groups in order to generate energy relationship between two certain groups, and this relationship can conserve stability under attacks. Experimental results indicate that the proposed scheme is robust to intentional attacks with no visual distortion influence.The rest of this paper is organized as follows. In H.264/AVC contains a number of new features that allow it to compress video much more effectively than older standards and to provide more flexibility for application to a wide variety of network environments. Tree structured block size, motion compensation, and distortion drift provide theoretical support for our watermarking scheme.H.264/AVC supports motion compensation block sizes ranging from 16 × 16 to 4 × 4 luminance samples with many options. The luminance component of each MB (macroblock) (16 × 16 samples) may be split up in 4 ways as shown in Each of the subdivided regions is a MB partition. If the 8 × 8 mode is chosen, each of the four 8 × 8 MB partitions within the MB may be further split in 4 ways as shown in These partitions and subpartitions give rise to a large number of possible combinations within each MB .In block motion compensation, the frames are partitioned into blocks of pixels . Each block is predicted from a block of equal size in the reference frame. The blocks are not transformed in any way apart from being shifted to the position of the predicted block. This shift is represented by a motion vector.To exploit the redundancy between neighboring block vectors , it is common to only encode the difference between current motion vector and previous motion vector in the bitstream. The result of this differencing process is mathematically equivalent to a global motion compensation that is capable of panning. Then, an entropy coder will take advantage of the resulting statistical distribution of the motion vectors around the zero vector to reduce the output size.In motion compensation, there are three kinds of motion vectors named MV, MVP, and MVD. Apparently, MV is the abbreviation of motion vector, which is a two-dimensional vector used for interprediction that provides an offset from the coordinates in the decoded picture to those in a reference picture. MVP means motion vector prediction, which represents the motion vector in the reference picture. MVD stands for motion vector difference, that is, the coded and transmitted motion vector residual. The relationship among these vectors is as follows:Altering the value of motion vector difference will make the embedded MB change, which means that a certain block in frame becomes different. What is more, this distortion is then propagated to the adjacent MBs and succeeding frames due to motion prediction compensation, even though these MBs and frames are not watermarked at all. This is called distortion drift and methods adopted to prevent such distortion from happening are called drift compensation.B = MVA. MVDA being increased by 1  is replaced by value at  calculated from the above formula.Assume that With such a transformation, a scrambled image can be generated through pixel permutation. If secret key is unavailable, no readable information can be obtained even after watermark being correctly detected.B is the process to generate binary sequence, and W is the watermark signal to be embedded.Finally, the binary image is converted into a scrambled binary sequence. This scrambled sequence is the watermark signal to be embedded; see As indicated in Actually, we have another reason to choose the right bottom sub-MB/subpartition to embed watermark. As mentioned above, changes in one MB may cause distortion drift once this MB is referred by other MBs. But the right bottom sub-MB/subpartition is the least possible one to be referred by adjacent MBs.Specifically, in the motion vector median prediction, suppose E in (1) The target video should be decoded until reaching the slice level.(2) When encountering I/B slice, skip to the next slice. Only if the current slice is P slice, proceed further decoding.(3) Decode MB syntax of P slice. Only the P MBs containing four 8 × 8 sub-MBs are selected. Find the right bottom sub-MB (8 × 8) and read motion vectors of the right bottom subpartition if subpartition exists. In (4) Take a line as a unit and start searching from the right bottom corner of the slice. If we succeed to collect 8 P MBs, continue to search the next line until we gather 32 MBs (4 lines are needed):(5) Divide these 32 MBs into two groups (16 MBs each), and then process horizontal MVDs of the right-bottom subpartition in each MB by modulus 10; that is, extract units digit of each MVD:(6) Convert each group into 4 × 4 matrix and perform DCT transform:A′′ and MVDB′′ are the sum of DC and 2 AC coefficients from group A and group B, respectively. T is the threshold which is set to 5 according to experimental results.(7) According to the watermark bit to be embedded, modify the value of DC coefficients and 2 low-frequency AC coefficients which are mostly adjacent to DC coefficients according to(8) Take IDCT transform, and then calculate the final motion vectors as follows:(9) Encode the current P slice.(10) Loop from step (2) until we reach the end of slice.Comparing with previous watermarking schemes based on motion vector, our scheme can survive intentional attacks such as lossy compression or motion estimation algorithm change. Because for traditional watermarking schemes which regard the parity of motion vector as payload, the only one bit difference in parity will vanish after being reencoded, the embedded watermark cannot survive after some normal operations, let alone intentional attacks.We adopt DCT in our scheme for its “energy compaction” property : most of(1) The watermarked video is decoded until slice level is reached.(2) Only decode the current slice when it is P slice and skip to the next slice for I/B slice.(3) Decode MB syntax of P slice. Search for P MBs containing 8 × 8 sub-MBs. Read motion vectors of each sub-MB and record horizontal MVD of the right bottom sub-MB.(4) Take a line as a unit and start searching from the right bottom corner. If we succeed to collect 8 P MBs, continue to search the next line until we get 32 MBs .(5) Divide these 32 MBs into two groups (16 MBs each), and then process horizontal MVDs of the right bottom subpartition in each MB by modulus 10.(6) Convert each group into 4 × 4 matrix and take DCT transform.(7) Make comparison between the sum of DC and the 2 nearest AC coefficients in two groups:(8) Loop from step (2) until we reach the end of slice.For the example mentioned in As shown in Since general circumstances are more complicated, the following steps should be taken to carry out drift compensation.Store information (MB number and amount of modification) of previous MB which has MVD changed because of watermark embedding.For the case that the reference MB of current MB has been watermarked according to the information recorded in (a) If the current MB is not selected to embed watermark, just perform reverse modification according to the reference MB.(b) If the current MB is selected to embed watermark, do the embedding modification and store information of current MB. However, the two modifications on current MB and the reference MB need to be accumulated; hence, drift compensations can be conducted together next time.However, even though it is possible to know which MB is taken as reference in the process of decoding, the reference MB will sometimes change to other MB when modification is performed. Thus the drift compensation may cause worse effects. The reason for such change in reference MB is that in the interprediction stage, three adjacent MBs are taken into consideration and MB with median motion vector value is selected as reference one. Modification on MVD will change MV so that this increase/decrease in motion vector value will impact the relationship of the three MBs and lead to the alteration of reference MB.If median prediction is disabled for the current MB, the reference MB before and after embedding will not change. Just go to If median prediction is chosen, retrieve MVs of three adjacent MBs and increase or decrease them according to the modification information stored. Thus through calculating actual median value, the reference MB after embedding can be determined.If reference MB stays the same, go to If change happens, denote new modification as the difference between MV of new reference MB and MV of the original reference MB. Then go to To solve such a problem, more work needs to be done before The drift compensation approach is illustrated in In this experiment, the H.264/AVC codec JM8.6 , officiaAccording to the experimental conditions mentioned, we set the default quantization parameter (QP) to 28, choose IPPP type as coding sequence, and select “Bus,” “Flower,” “Mobile,” and “Stefan” sequences for testing. A video quality analysis software named “Elecard Stream Tools” is employed in our experiment.To evaluate the change of video quality before and after being watermark embedded, we introduce four new objective evaluation indicators:(i) NQI: new quality metrics;(ii) VQM: Video Quality Measurement techniques;(iii) SSIM: structural similarity;(iv) MOVIE: motion-based video integrity evaluation .These four indicators can present numerical difference between the original and watermarked video. With the use of Elecard Video Quality Estimator, we encoded video sequences with different QP values. Results are shown in NQI takes the brightness distortion, contrast distortion, and relativity loss into account, ranging from −1 to 1. NQI closer to 1 means a higher video fidelity. As indicated from VQM is used to measure perceptual effects of video impairments including blurring, unnatural motion, global noise, block distortion, and color distortion. VQM closer to 0 means a smaller distortion and it is sensitive to QP value. As shown in SSIM is a new indicator measuring the similarity of two video frames whose range is . It is based on measuring three components  and combining them into result value. SSIM closer to 1 indicates a higher similarity of two videos. From data in MOVIE is a general, spatiospectrally localized multiscale framework for evaluating dynamic video fidelity that integrates both spatial and temporal  aspects of distortion assessment. Better video fidelity is obtained when value of MOVIE is closer to 0. As shown above, the MOVIE ranges from 0.000890 to 0.005121. So we can conclude that the video fidelity has been little influenced after being watermarked.Drift compensation is adopted in our scheme to avoid distortion drift and to improve the quality of watermarked video. As mentioned before, NQI closer to 1 indicates a better imperceptibility. As shown in Lower VQM value indicates better video quality and We find that SSIM value drops fiercely if drift compensation is not carried out in our scheme as shown in As indicated above, lower MOVIE is obtained when drift compensation scheme is applied. The largest difference in To analyze the imperceptibility of our scheme, we compare our scheme with Sun et al.'s algorithm .In this experiment, we use sequence “Bus” with QP ranging from 24 to 32. As shown in Conclusions can be drawn from all of the data above.(1) For most of the time, NQI is above 0.97, VQM is below 0.5, SSIM is above 0.98, and MOVIE is below 0.005. All these four indicators demonstrate that our scheme has excellent imperceptibility.(2) For scheme without drift compensation, NQI drops to 0.06, VQM increases to 1.3, SSIM decreases to 0.08, and MOVIE increases to 0.001704 at most. Our scheme with drift compensation gains better video quality.(3) In comparison with Sun et al.'s  scheme, In this experiment, all four sequences “Bus,” “Flower,” “Mobile,” and “Stefan” are used. After watermark is being embedded, these videos are decoded and reencoded with different QP values and motion estimation algorithms to generate recompression.To verify the robustness under lossy compression, the watermarked video is recompressed with different QP values. w is the bit number of a certain watermark, and c is the number of bits correctly detected.In R stands for the recompression rate, Sw and So denote watermarked video size and original video size, respectively.As can be seen from Motion estimation algorithm is the most relevant factor for motion vector because different motion estimation algorithms will cause huge change to the final motion vector.In this experiment, we keep the QP value unchanged and choose different motion estimation algorithms in the process of encoding. We firstly use JM8.6 to generate video files with embedded watermark and decode video files into YUV sequences. A video encoder software named X264 is then used to encode these YUV sequences into video files again. However, different motion estimation algorithms are chosen in this encoding process so that intentional attack can be performed.The default motion estimation algorithm of JM8.6 is “Fast Full Pel Block Motion Search,” whereas X264 has five different motion estimation algorithms named “Diamond Search,” “Hexagonal Search,” “Uneven Multi-Hexagon Search,” “Exhaustive Search”, and “Transformed Exhaustive Search.”As indicated in As mentioned before, few research works focused on robust watermarking scheme based on motion vector, so it becomes extremely difficult to do comparison experiments with other proposed algorithms. The most relevant literature we found is proposed by Li et al.  which foIn our experiment, an extreme lossy compression rate 80% is tested and such high compression rate will cause great decline in video quality. Nevertheless, the correctness of watermark detection can still keep above 70% under such a circumstance. In the meantime, the watermark retrieval correctness has a high stability under different motion estimation algorithms. Conclusion can be drawn that our scheme has an excellent robustness against intentional attacks.The capacity of a watermarking scheme decides the application scope of the algorithm. With our proposed scheme, different bits of watermark are embedded into video and visual impact is observed carefully. As a result, two-bit watermark can be embedded into each P frame and little visual decrease can be noticed. But if we try to embed 3 bits in each frame, the imperceptibility of our scheme will suffer a slight decrease occasionally.As illustrated in Videos are usually displayed at a rate of more than 24 frames per second so that at least 22.5 bits of covert information can be embedded within one second in video. With content of watermark elaborately designed, we may embed one entire watermark within several seconds (video time).Bit rate is an important feature of video quality, especially for those low bit rate H.264 videos which have a high request on rate control. The watermark embedding is bound to affect the video bit rate. The ability to control bit rate effectively and strictly is also an important indicator of H.264 video watermarking scheme.In this paper, a robust video watermarking scheme with drift compression is proposed. The devised MB selection scheme can lower the influence on video quality and reduce the possibility of drift distortion. In the meantime, a new drift compensation scheme is adopted to improve the imperceptibility of watermarking. Besides, the “energy compaction” property of DCT is utilized to embed the watermark into motion vector residual with good robustness against intentional attack. The experimental results indicate that the video quality is almost the same as that of the original one, and the increase of bit rate is less than 0.2%, which keeps the high video compression rate of H.264. This scheme is also robust against malicious attack with different QPs or motion estimation algorithms. Even with a high recompression rate of 80%, the correctness of watermark detection can still reach 70%.Our future work will focus on the robustness against other video attacks and improving the performance of video sequences containing fierce movements.


This special issue is an attempt to cover some new aspects concerning benign hepatocellular tumors: focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA).In this special issue, we were fortunate enough to have editors from different countries  and from different disciplines  who have contributed 6 papers and 5 contributors from academic centres involved in benign hepatocellular tumors, namely, liver pathologists, radiologists, and molecular biologists from different continents: Europe, North America, and Asia. Concerning FNH, if their diagnosis is mainly made by radiologists, some particular cases required a biopsy or even resection. When standard pathological features are atypical, the diagnosis is greatly facilitated by immunohistochemistry, particularly the characteristic pattern of glutamine synthetase (GS), in biopsy as well as surgical specimens, as described by the Bordeaux group.HCA is the main topic of this issue. This benign rare liver tumor came to medical attention in 1973 when it became clear that oral contraceptives introduced in the USA in 1960 were the main agents responsible for the occurrence of HCA. The first complication identified was bleeding, which was occasionally life threatening, was often the first manifestation of tumor, and often led to surgical resection. The second complication, hepatocellular carcinoma (HCC) transformation, reinforced a surgical approach to treatment in spite of the fact that malignant transformation remains a subject of controversy. HCA is a worldwide problem with a clear difference in incidence between Europe and Asia. This difference is mainly explained by the different methods of contraception in the world. In Europe oral contraceptives (OC) are taken by 54, 58, 60, 68, and 75 percent of women in France, Holland, Belgium, Portugal, and Germany, respectively, versus 1% in China, 2% in Japan, and 21% in USA. In a study from Japan published in this issue, only 2 of 13 cases of HCA described were found in women taking OC. Presently there is no data concerning the influence of the OC generation on the incidence of HCA. It was thought that the lower levels of estradiol should decrease the risk of HCA. This was not observed. The possible explanation comes from the identification of novel risk factors, namely, obesity and metabolic syndrome.Exploring the combined experience of US centers, publications reporting HCA in the US were identified through a PubMed search and a review of the literature. Whereas earlier reports of HCA in the US described cases exclusively in women exposed to OC, there is a trend towards an increase in HCAs reported in men, HCAs in the absence of OC use, and increased reports of multiple HCAs. This confirms the experience from European centers and may be a result of newer OC formulations and increasing prevalence of obesity.CTNNB1 mutations, or (3) activation of the IL6/STAT3 pathway by somatic mutation of IL6ST, GNAS, or STAT3. The genotype classification led to the phenotypic classification, now well recognized and with specific characteristic immunomarkers. Interestingly, different centres have obtained similar results from the first one published in France. For example in Brussels, as published in this issue, from January 1992 to January 2012, 37 patients underwent surgical resection for HCA. Nine had HNF1α-inactivated HCA (H-HCA: 25%) with lack of LFABP expression; 20 had inflammatory HCA (IHCA: 55.5%) showing CRP and/or SAA expression; in 5 patients (14%), β-catenin-activated HCA (b-HCA) with GS and nuclear β-catenin positivity was diagnosed, two already with HCC. Two cases (5.5%) remained unclassified. One b-HCA exhibited the IHCA histological and immunohistochemical characteristics corresponding to the subgroup of β-catenin-activated/inflammatory HCA. Not surprisingly, as suggested in this issue, the percentage of the different subtypes may differ in HCA not linked to OC use such as in glycogenosis, familial adenomatous polyposis, vascular diseases , drug intake (danazol), in men and young children. Molecular classification is opening a new field of investigation among these examples of nodules which are not presently well characterized. Interest in HCA has expanded recently in the first decade of this new century when it was discovered that HCAs are different entities under the control of distinct gene mutations. A molecular classification related to risk factors, pathological features, and risk of transformation in HCC was revealed. As reported in the paper describing molecular classification, three major pathways have been identified which define specific HCA subgroups (1) inactivation of hepatocyte nuclear factor 1A (HNF1A)/transcription factor, (2) activation of the Wnt/b-catenin pathway by  In this issue, it was confirmed that MRI was the method of choice to identify HCA (and differentiate from FNH) and that it was possible to identify the 2 major subtypes (H-HCA and IHCA) in the absence of major remodeling due to bleeding/necrosis. A biopsy can be useful when the diagnosis of HCA and HCA subtypes cannot be made.  It was shown that H&E routine histology allows to diagnose >85% of the 2 major HCA subtypes. However, GS is essential to identify b-HCA and b-IHCA. This study demonstrates that a “palliative” diagnostic approach can be proposed, when the panel of specific antibodies is not available. IHCA comprised about 50% of all HCAs and is often associated with obesity as already mentioned. Mild/moderate steatosis is found in the nontumoral liver in a high frequency which is in accordance with the high BMI; of note are the regular findings of sinusoidal dilatation, single arteries, and minute CRP foci which are all features of HCA, as reported by the Groningen's group. These distinct CRP foci are mostly found in cases of multiple IHCA. In academic centers, particularly referral centres for primary liver tumors, immunohistochemistry is essential to understand the natural history of the different HCA subtypes, particularly in women taking OC, and notably with regard to risk for malignant transformation. In this issue, the Paris pediatric group studied benign hepatic tumors in children. They are very rare. Most FNH remains sporadic, but predisposing factors exist: long-term cancer survivors, portal deprivation in congenital or surgical portosystemic shunting. HCA is frequently associated with predisposing factors such as glycogenosis type I and III, Fanconi anemia , congenital portal shunt, and SPSS; of note, the same vascular abnormality can induce 2 different types of nodules. HNF1-A gene (associated or not with MODY3). Adolescents or adults with MODY3 should be tested for the presence of HCA. Conversely young diabetic patients with H-HCA should be tested for MODY3. Adenomatosis has been mainly reported in germline mutations of The Rotterdam group focused its interest on HCA in pregnancy. They come to the important conclusion that pregnancy in women with an HCA up to 5 cm is no longer discouraged in close consultation with the patient, her partner, and members of the liver expert team. In this review you will find also practical guidelines dealing with the diagnosis and management of HCA subtypes in the paper written by authors from different countries. We hope that his review will encourage multidisciplinary teams to work in this field. We need to establish guidelines  in different etiological conditions including yet unknown diseases. As an example, the Japanese team found that in patients with alcoholic cirrhosis, a group of possible inflammatory HCAs was characterized by strong immunoreactivity for serum amyloid A (SAA). They suggested that these SAA-positive hepatocellular neoplasms in alcoholic cirrhosis may be a new entity of HCA, which may have the potential for malignant transformation. They correctly indicate that further studies are needed to clarify genetic changes, monoclonality, and pathogenesis of this new type of hepatocellular neoplasm. Understanding malignant transformation of HCA indeed remains a major objective for the coming years.Paulette Bioulac-SagePaulette Bioulac-SageLuigi GrazioliLuigi GrazioliTürkan TerkivatanTürkan TerkivatanCharissa ChangCharissa Chang


To explore the relationship between prematurity, gender and chorioamnionitis as determinants of early life lung function in premature infants.Placenta and membranes were collected from preterm deliveries  and evaluated for histological chorioamnionitis (HCA). Patients were followed and lung function was performed in the first year of life by Raised Volume-Rapid Thoracic Compression Technique.p = 0.012 for FEF50, p = 0.014 for FEF25–75 and p = 0.32 for FEV0.5). Two-way ANOVA adjusted for length and gestational age indicated a significant interaction between sex and HCA in determining expiratory flows . Post-hoc comparisons revealed that female preterm infants exposed to HCA Grade 1 and Grade 2 had significant lower lung function than those not exposed, and this effect was not observed among males.Ninety-five infants  born prematurely  were recruited. HCA was detected in 66 (69%) of the placentas, and of these 55(58%) were scored HCA Grade 1, and 11(12%) HCA Grade 2. Infants exposed to HCA Grade 1 and Grade 2, when compared to those not exposed, presented significantly lower gestational ages, higher prevalence of RDS, clinical early-onset sepsis, and the use of supplemental oxygen more than 28 days. Infants exposed to HCA also had significantly lower maximal flows. There was a significant negative trend for z-scores of lung function in relation to levels of HCA; infants had lower maximal expiratory flows with increasing level of HCA. (Our findings show a sex-specific negative effect of prenatal inflammation on lung function of female preterm infants. This study confirms and expands knowledge upon the known association between chorioamnionitis and early life chronic lung disease. Premature birth can lead to a wide range of early life consequences for the immature lung and most of these are likely associated with increased respiratory morbidity in the first years of life. Of all main factors related to poor lung development in premature infants, gestational age is the best predictor of respiratory outcomes, but sex also plays an important role. Another aspect that may influence respiratory morbidity in the first years of life is the fact that infant girls, who are more likely to be born with the benefit of larger airways compared to boys, seem to lose this advantage if exposed to pre-natal maternal smoking In this study, we explore the relation between prematurity, sex and chorioamnionitis as determinants of lung function during the first year of life, assessed by objective measurements. We hypothesized that maximal expiratory flows are reduced in those preterm infants exposed to inflammation, and that the effect is modulated by sex and gestational age.The study was approved by the ethics committee of our institution  and an informed written consent was obtained from all parents.We conducted a prospective cohort study including all newborn premature infants . All patients were recruited at birth in a single academic hospital in Porto Alegre, Brazil, for a period of 12 months.Gestational age was determined by last menstrual period, and confirmed by early obstetric ultrasound (in the first 12 weeks of gestation) and clinical assessment by a neonatologist. thpercentile for gestational age. All NICU procedures and events were recorded prospectively by one of the investigators (ALC). A newborn was considered to have Respiratory Distress Syndrome (RDS) when there was requirement of FIO2≥0.40, presence of characteristic chest X-ray, and need of exogenous surfactant replacement. Small-for-gestational-age (SGA) was defined by birth weight below the 10Five tissue samples were obtained from each placenta , fixed with 10% buffered formalin, embedded in paraffin and tissue block and stained with hematoxylin and eosin. Histologic examination was performed by a pathologist (MIE) blinded to the clinical information and scored as “no chorioamnionitis”, “Grade 1” (Redline Lung function testing was assessed by the Raised Volume-Rapid Thoracic Compression Technique (RV-RTC), after sedation with chloral hydrate (50–80 mg/kg). 2O and, at this point, thoracic compression was initiated and maintained until residual volume was reached. Forced expiratory maneuvers were repeated with increases of 5 to 10 cm H2O in jacket pressure until maximum expiratory flows were obtained. The best curve was selected as that with the highest product of Forced Vital Capacity (FVC) and Forced Expiratory Flow Between 25% and 75% of FVC (FEF25–75) Lung inflation pressure was set at 30 cm Hvs. female, HCA vs. no HCA) were compared by Mann-Whitney test, and Pearson Chi-square. Z-scores of the lung function variables were used, as a length-adjustment approach. Statistical analysis of the data was performed using the statistical program SPSS, version 17 . Quantitative and qualitative variables were described, respectively, through means/SD, median/range and frequencies/percentiles. Group characteristics , SGA, clinical early-onset sepsis, PDA, maternal corticosteroid use, prolonged premature rupture of membranes (>18 h).The data were analyzed by two-way ANOVA (sex by HCA) and ANCOVA, including length and gestational age as covariates. For post-hoc analysis, the Holm-Sidak test was used. For all statistical analyses, p-values below 0.05 were considered significant.95 premature infants were recruited  at the time of birth. Median (range) gestational age was 34.2 (24 to 36.8) weeks and median birth weight was 2,255  grams. Fifty-five (58.3%) of the subjects were white. RDS was observed in 15 (16%) infants. While 26 (27%) had a diagnosis of clinical early-onset sepsis, blood culture was positive in only two subjects. Supplemental oxygen for more than 28 days was required by 10 (10.5%) of these infants. HCA was detected in 66 (69%) of the placentas, and of these 55(58%) were scored Grade 1, and 11(12%) Grade 2. Fetal inflammatory response was detected in only 6 infants, two with chorionic vasculitis, three with umbilical vasculitis and one with necrotizing funisitis.As shown in p = 0.012 for FEF50, p = 0.014 for FEF25–75 and p = 0.32 for FEV0.5)(In r FEV0.5).p = 0.049 for males and r = −0.336, p = 0.015 for females). HCA level was also significantly correlated to lower maximal flows in female preterm infants  but not in males.There was a significant negative correlation between HCA and Gestational age in both sexes , 109 mL/s (34%) and 20 mL (12%), respectively. FVC values were not significantly different for male and female subjects. In this multivariate analysis, adjusting for sex, length, and gestational age, there was no significant effect on lung function of HCA, race, smoking exposure during pregnancy, PPROM, RDS, antenatal steroids, supplemental oxygen for more than 28 days and SGA on measured lung function variables.The differences between sexes in lung function values remained significant after adjusting for length, weight (expressed as Z score), and gestational age in a multivariate model. Female preterm infants had, on average, expiratory flows 119 mL/s (31%) higher than males for FEF50 and FEF25–75 and p<0.05 for FEV0.5). The interaction between sex and HCA was significant with both HCA categorized in three levels  or two levels . Post-hoc comparisons by Holm-Sidak test revealed that female preterm infants exposed to HCA Grade 1 and Grade 2 had significant lower lung function than those not exposed, and this effect was not observed among males. Unexposed female preterm infants had significantly higher maximal expiratory flows when compared to males and exposed females. The results are presented in Two-way ANOVA adjusted for length and gestational age indicated a significant interaction between sex and HCA in determining expiratory flows  compared to those not exposed, but this was not observed in boys. In the same line of thought, female infants who were adequately breastfed were protected against severe bronchiolitis (a quite likely surrogate for lower lung function) in contrast with those who were not Similar to our main finding of lower lung function among baby girls exposed to HCA, exposure to maternal smoking during pregnancy has been associated with lower lung function, an effect that seems more clearly detected also in female infants. Previous studies point to an association between prematurity and chorioamnionitis and obstructive respiratory illnesses in children. We found a large number of subjects exposed to HCA in our sample (65%). This could be a result of lower social conditions, poorer public health care, or even race, as previously reported One limitation of this study is the lack of a satisfactory marker for duration and intensity of the inflammatory exposure. The intensity of neutrophilic infiltration at the time of delivery cannot be used to estimate the extension or severity of inflammation during the whole pregnancy period. The histological findings obtained at birth are poor descriptors of the intrauterine milieu and lung fetal exposure throughout the gestation period. In summary, our study presents original data on the association between HCA and lung function measured in the first year of life, assessed by the RV-RTC technique in preterm infants. We have found a reduction in maximal expiratory flows in female preterm infants exposed to HCA, an effect not observed in males. These results imply that there may be a selective negative effect of inflammation on the development of the lung, especially among female preterm infants.


Alcohol drinking is frequently related to behavioral problems, which lead to a number of negative consequences. This study was to evaluate the characteristics of male high school students who drink, the drinking patterns among them, and the associations between current drinking and other health risk behaviors which focused on personal safety, violence-related behaviors, suicide and sexual behaviors.A cross-sectional study was conducted to explore current alcohol drinking and health-risk behaviors among male high school students in central Thailand. Five thousand one hundred and eighty four male students were classified into 2 groups according to drinking in the previous 30 days . Data were collected by self-administered, anonymous questionnaire which consisted of 3 parts: socio-demographic factors, health-risk behaviors and alcohol drinking behavior during the past year from December 2007 to February 2008.The results showed that the percent of current drinking was 12.17. Most of them were 15-17 years (50.21%). Socio-demographic factors such as age, educational level, residence, cohabitants, grade point average (GPA), having a part time job and having family members with alcohol/drug problems were significantly associated with alcohol drinking (p < 0.05). Multiple logistic regression analysis, after adjusting for socio-demographic factors, revealed that health-risk behavioral factors were associated with current alcohol consumption: often drove after drinking alcohol , often carried a weapon , often got into a physical fight without injury , dating violence , seriously thought about suicide , made a suicide plan , ever had sexual intercourse , alcohol or drug use before last sexual intercourse , and got someone pregnant .An increased risk of health-risk behaviors, including driving vehicles after drinking, violence-related behaviors, sad feelings and attempted suicide, and sexual behaviors was higher among drinking students that led to significant health problems. Effective intervention strategies  among adolescents should be implemented to prevent underage drinking and adverse consequences. It is well established that an increase in alcohol consumption leads to a higher proportion of persons with problem use and addiction. In 2007, the National Statistical Office of Thailand found 29.3% of Thais ≥ 15 years old consume alcohol. The proportion of male alcohol consumption in the age 25-59 years was 59.1%, 15-24 years 39.2% and over 60 years 29.4%, respectively [The aim of this study was to evaluate the characteristics of male high school students who drink, the drinking patterns among them, and the associations between current drinking and other health risk behaviors which focused on personal safety, violence-related behaviors, suicide and sexual behaviors.A cross-sectional study was conducted from December 2007 to February 2008 in order to explore current drinking and health-risk behaviors among male high school students in central Thailand. The proposal was reviewed and approved by the Ethics Committee for Research in Human Subjects of Mahidol University (Ref.No. Mu 2007-243). A two-stage stratified sampling technique was used to select the 5,184 students from 10 provinces of central Thailand within the academic zones 5, 6, and 12. The primary sampling unit was province and the second was school. These provinces were randomly selected and represented characteristics of male adolescents in central Thailand. In each province, we randomly selected at least one school from the list of each of the three school categories: urban and rural public schools, and private schools. The selection of schools was based on a list of schools obtained from the Provincial Education Offices and willingness of school administrators to participate in the study. Selected schools could refuse to participate in the study. Altogether, 5,184 students from Mathayomsuksa School (MS) 1, 3 and 5 participated in the study . In each school, 3 or fewer classes of each of these 3 educational levels were recruited from the same grade level. If there were more than three classes, three classes with students of mixed academic performance were randomly selected by their teachers. The study subjects were classified into 2 groups according to their alcohol intake during the 30 days preceding the survey . Information was collected by a self administered, anonymous questionnaire which consisted of 3 parts, socio-demographics, health-risk behaviors during past year and alcohol drinking behavior with the help and supervision of well trained research assistants. Current drinking was defined as drinking at least one standard drink of an alcoholic beverage during the past 30 days of the survey. A standard drink was defined as a can (330 cc) of beer, a glass (100 cc) of wine, or a small glass (30 cc) of whisky or spirits. The health-risk behaviors questionnaire was modified from the questionnaire of the U.S. Youth Risk Behavior Surveillance System [Socio-demographic factors were given as a percentage, crude odds ratio, 95% CI of OR and p-value. Univariate analysis was performed using the Pearson's chi-square test to differentiate proportional exposures between drinkers and non-drinkers for categorical variables. Adjusted odds ratio and the 95% CI of OR were calculated from multiple logistic regression to examine associations between current drinking and health-risk behaviors, adjusted for socio-demographic factors. A criteria of p < 0.05 for statistical significance was applied.th graders vs 22.08% among 11th graders).A total of 5,184 male high school students, their percents of alcohol consumption in the past 30 days were 12.17. Current drinking prevalence increased with increasing age (6.41% among less than 15 year-olds vs 26.54% among 18 years and older) and grade level  were age group , educational level , residence , cohabitants , as well as GPA , having a part time job  and having family members with alcohol/drug problems  , compared with non-drinkers, current drinkers were more likely to drive a car/bicycle after drinking alcohol . For violence-related behaviors, often carrying a weapon , often getting into a physical fight without injury , and experience dating violence  were proportionally higher among current drinking students than non-drinkers. In addition, sad feelings and attempted suicide, indicated that participants had seriously thought about suicide  and making a suicide plan  were also significantly associated with current drinking. In case of sexual behaviors, higher proportions of ever having sexual intercourse , alcohol or drug use before last sexual intercourse , and getting someone pregnant  were found among current drinkers than among non-drinking students, as shown in Table The majority of boys drank alcohol less than 3 times a month 59.83%) and they each consumed less than 3 standard drinks in the previous month (38.59%). Approximately 40% of boys drank more often than twice a month and 39% of them drank more than 4 standard drinks each time. Alcohol consumption was more common when joining a party (45.68%) but a high proportion of boys drank at home/dormitory (36.33%). Nearly 70% of respondents experienced binge drinking within 2 weeks and nearly half of them admitted to being intoxicated during the 30 days prior to participating in this study, as shown in Figure 9.83% andet al, 2007 [et al, 2008 [et al, 2007 [et al, 2009 [The present study found an increased risk of health-risk behaviors, including intentional injury-related behaviors, suicidal behaviors and premature sexual behaviors among drinking and non-drinking students. This study is one of a few studies on underage drinking among high school students in a developing country of the South-East Asian region. Our findings demonstrated that approximately 12% of male high school students reported that they drank alcohol during the 30 days preceding the survey. This figure was also lower than the studies of Miller al, 2007 , Johnstoal, 2008  and Assaal, 2007 ,9-13. Noal, 2009 . Eaton fal, 2009 . Alcoholal, 2009 -18, gettal, 2009  and datial, 2009 ,19-21. Ial, 2009 ,22-24. Ial, 2009 ,20,25, aal, 2009  and gettal, 2009 .Some limitations of this study should be noted. First, the study was a cross-sectional study, therefore, a temporal relationship cannot be established between alcohol consumption and the health-risk behaviors. A longitudinal study would be needed to examine causal effects of drinking on subsequent drinking. Second, all data were obtained through self-reports, which may lead to inaccuracies of alcohol drinking -31 and oAn increased risk of health-risk behaviors, including driving vehicles after drinking, violence-related behaviors, sad feelings and attempted suicide, and sexual behaviors was higher among drinking students that led to various health problems. The results from this study show prevention of underage drinking is needed. Law enforcement, namely minimum age of purchasing alcohol ≥ 20 years, increasing the penalty of drunk driving, and limiting the availability and accessibility of alcohol through restrictions of times and places should be done strictly. The results suggested that effective intervention strategies among adolescents should be implemented to prevent underage drinking. Applications of the health promoting school model of WHO  should bThe authors declare that they have no competing interests.WC was involved in drafting the manuscript and revising it critically for important intellectual content. All authors were involved in the design of the study, statistical analysis and data interpretation. All authors have read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/11/233/prepub


A sizable literature has analyzed the frequency of alcohol consumption and patterns of drinking among veterans. However, few studies have examined patterns of alcohol use in veterans of the first Gulf War or factors associated with problem drinking in this population. We examined the frequency and patterns of alcohol use in male and female veterans who served in the 1991 Gulf War or during the same era and the relationships between alcohol use and selected health conditions.We analyzed data from a follow-up survey of health information among population-based samples of 15,000 Gulf War and 15,000 Gulf Era veterans. Data had been collected from 9,970 respondents during 2003 through 2005 via a structured questionnaire or telephone survey.Posttraumatic stress disorder (PTSD), major depressive disorder (MDD), unexplained multisymptom illness (MSI), and chronic fatigue syndrome (CFS)–like illness were more frequent among veterans with problem drinking than those without problem drinking. Approximately 28% of Gulf War veterans with problem drinking had PTSD compared with 13% of Gulf War veterans without problem drinking. In multivariate analysis, problem drinking was positively associated with PTSD, MDD, unexplained MSI, and CFS–like illness after adjustment for age, sex, race/ethnicity, branch of service, rank, and Gulf status. Veterans who were problem drinkers were 2.7 times as likely to have PTSD as veterans who were not problem drinkers.These findings indicate that access to evidence-based treatment programs and systems of care should be provided for veterans who abuse alcohol and who have PTSD and other war-related health conditions and illnesses. An increasing number of studies have examined the frequency and patterns of alcohol consumption in various veteran populations and the relationship between problem or hazardous drinking and other health conditions including posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) -6. StudiStudies of alcohol consumption in US veterans of the 1991 Gulf War have varied according to sample selection procedures  and by sample size, presence or absence of a nondeployed comparison group, calendar year of the survey or number of years since the conflict ended, approaches for data collection , and other study design features –like illness and unexplained multisymptom illness (MSI), that have been associated with service in the 1991 Gulf War. Both CFS–like illness and MSI may occur as comorbid conditions among people with problem drinking.We analyzed data from a follow-up health survey among population-based samples of 15,000 Gulf War veterans and 15,000 Gulf Era veterans (veterans who served during the same era but who were not deployed to the Persian Gulf). Data were collected from 9,970 respondents in 2003 through 2005 via a structured questionnaire or telephone survey. We examined the frequency and patterns of alcohol use in Gulf War and Gulf Era veterans and associations between problem drinking and selected health conditions, including PTSD and MDD.The design of this study was cross-sectional. We obtained data from a follow-up survey to the 1995 National Health Survey of Gulf War Era Veterans and Their Families . The samProcedures for ascertaining the vital status and updated address of each of the sampled respondents have previously been reported ,21. A toData collection began in June of 2003. We used a modified Dillman method and sent a prenotification letter to each potential participant, which was followed by questionnaire mailings conducted in 3 waves . The firThe survey questionnaire included questions about functional status, activity limitations, health perceptions, height, weight, chronic medical conditions, PTSD and other mental disorders, and health care use. We asked the respondents whether they ever drink alcohol (including beer or wine) and, if so, they were asked about the average number of drinks they consume per week. We asked the respondents whether any of the following had happened to them more than once during the past 6 months: 1) You drank alcohol even though a doctor suggested that you stop drinking because of a problem with your health; 2) You drank alcohol, were high from alcohol, or hungover while you were working, going to school, taking care of children, or engaged in other responsibilities; 3) You missed or were late for work, school, or other activities because you were drinking or hungover; 4) You had a problem getting along with other people while you were drinking; and 5) You drove a car after having several drinks or after drinking too much.We used the PTSD checklist (PCL) to assess symptoms of PTSD. Respondents rate PCL items on a 5-point Likert scale to indicate the degree to which they have had each of 17 PTSD symptoms during the past month . PossiblWe used the Patient Health Questionnaire (PHQ) to assess MDD and other mental disorders. The PHQ is a brief self-report assessment of common mental disorders developed specifically for primary care . PHQ allWe modified the 1994 Centers for Disease Control and Prevention case definition of CFS illness  for use We defined unexplained MSI by using self-reported information about unexplained physical symptoms and illnesses  that persisted for 6 months or longer and that are not adequately explained by an established, conventional medical or mental disorder diagnosis. Such unexplained physical symptoms and illnesses, which are often not labeled, are sometimes diagnosed as CFS, fibromyalgia, irritable bowel syndrome, or multiple chemical sensitivity.Variables used in this analysis were age, sex, race/ethnicity , education , income , unit component , branch of service , rank , deployment status (Gulf War or Gulf Era), CFS–like illness, unexplained MSI, PTSD, and MDD. We included categorical variables for frequency of alcohol consumption and problem drinking. We categorized respondents as nondrinkers, light drinkers (1-2 drinks per week), moderate drinkers (<3-14 drinks per week), and heavy drinkers (≥15 drinks per week on average). We defined problem drinking as an affirmative response to any of the 5 previously mentioned questions about problem drinking or hazardous drinking in the past 6 months. Exploratory analyses were conducted to examine the patterns of alcohol consumption and problem drinking among the veterans.For the multivariate analyses, we performed logistic regression to examine problem drinking as a predictor of the health conditions and illnesses of interest  while controlling for all other variables included in the model . We used the Hosmer-Lemeshow goodness of fit test to assess model adequacy . We usedIn 2005, the mean age of Gulf War veterans was 45.5 years, and the mean age of Gulf Era veterans was 47.6 years. Self-reported information from Gulf War and Gulf Era veterans indicated that alcohol consumption was similar between the 2 groups . ApproxiHeavy alcohol consumption and problem drinking were more frequent among Gulf War veterans who had served as enlisted personnel compared with those who had served as officers or warrant officers. Approximately 17%  of veterans who had served as enlisted personnel in the Gulf War reported problem drinking compared with 11% (94 of 872) of veterans who had been officers and 6% (5 of 86) of veterans who had been warrant officers. Heavy alcohol consumption and problem drinking were also more frequent among Gulf War veterans who had less education or lower income. For example, 17% (13 of 75) of Gulf War veterans with less than a high school education reported problem drinking compared with 11% (86 of 778) of veterans with a master's, doctorate, or professional degree.Without adjusting for the variables, PTSD, MDD, unexplained MSI, and CFS–like illness were more frequent among veterans with problem drinking than those without problem drinking . ApproxiIn multivariate analysis , problemWe used cross-sectional data from a health survey of veterans that was conducted 13 years after the end of the 1991 Gulf War to examine the relationships between PTSD, MDD, and alcohol consumption. Therefore, the cases of PTSD identified in this cohort of Gulf War and Gulf Era veterans represent those that occurred as a result of war-time trauma and that persisted for an extended time, combined with PTSD cases that resulted from traumatic experiences that may have occurred after the war.PTSD is an anxiety disorder that can occur after someone experiences a traumatic event such as a combat experience, a motor vehicle crash, or sexual assault . SymptomOur findings indicate that, several years after the Gulf War ended, there was a high frequency of problem drinking among Gulf War and Gulf Era veterans who have PTSD, major depression, and other illnesses and health conditions. Psychological hypotheses about the relationship between alcohol abuse and PTSD often posit that PTSD precedes the development of alcohol abuse . AccordiOur study, which was a national sample of Gulf War veterans, was conducted by using mail questionnaires and telephone interviews rather than face-to-face evaluations. The Iowa Gulf War Case Validation Study, conducted during 1999-2001, used face-to-face evaluations with 602 veterans sampled from a population-based survey of 4,886 military personnel and found that lifetime history of alcohol abuse or dependence was frequent among both deployed and nondeployed veterans who were depressed . A study of the postwar hospitalization experience of US veterans who served in the 1991 Gulf War, which was based on medical records databases, found that alcohol dependence syndrome was the most frequent mental disorder; hospitalization rates for alcohol dependence were somewhat higher than those observed for other veterans from the same era who did not go to the Persian Gulf  . PTSD, mOur study confirms that some veterans who experience MSI or CFS–like illness also experience problem drinking as a comorbid condition. The exposures that account for increased risks of MSI and CFS–like illness among Gulf War veterans are unknown but may include environmental factors such as pyridostigmine bromide or exposure to certain pesticides . Many ofOur study has limitations. The cross-sectional nature of the analysis prevents us from making inferences about the causality of the observed associations. Another limitation is that PTSD was assessed by using the PCL screening test rather than clinical interviews; therefore, misclassification of PTSD status may have occurred. Also, information was not collected about binge drinking, which has been found to be a risk factor in other military and veteran populations . FurtherIn summary, the results of this survey conducted during 2003-2005 indicate that veterans of the 1991 Gulf War, particularly those who have PTSD or MDD, have a higher frequency of heavy alcohol consumption and problem drinking. These findings underscore the importance of sustained efforts to provide access to evidence-based treatment programs and systems of care for veterans who abuse alcohol and who have PTSD and other war-related health conditions and illnesses ,27,31.


This study investigated the association between the age at first drink and later alcohol drinking patterns, and analyzed whether differences in the association exist among Korean adults according to gender. The subjects included 10,649 adults  from the fourth Korean National Health and Nutrition Examination Survey between 2007 and 2009, which extracted the standard survey household by using the proportional systematic sampling method. Baseline individual characteristics, the age at first drink, and individual alcohol drinking patterns were obtained by specially trained interviewers or examiners. The association between the age at first drink and the adult alcohol drinking patterns was summarized with odds ratios and their confidence intervals obtained from multiple logistic regression analysis with sampling weights of KNHANES complex sample survey design. The results of this study show that age, co-habitation, occupation, smoking, and self-rated stress level were significantly related to the drinking patterns for men, whereas education, co-habitation, smoking, and self-rated stress level were significant factors for the drinking patterns of women. The association between the age at first drink and the adult alcohol consumption was significant for both genders and, interestingly, the alcohol drinking patterns were significantly differed by gender even after controlling for the individual characteristics. These results imply a need for gender-specific strategies to prevent hazardous alcohol consumption at a later time for Korean. Alcohol use disorders are leading preventable causes of death and disability worldwide Numerous studies have demonstrated a correlation between the age at first drink and alcohol use disorders later in life Starting to drink at an early age may lead to prolonged neurobiological effects specific to the adolescent brain Data were obtained from the fourth Korean National Health and Nutrition Examination Survey (KNHANES IV) between 2007 and 2009. The KNHANES is a nationwide representative survey using a stratified and multistage probability sampling design for the selection of household units. The survey was conducted by the Korean Ministry of Health and Welfare to establish national health policy based on the evaluation of health risk factors and health indicators. The survey data were obtained by specially trained interviewers or examiners who were not provided with any prior information about the survey participants and all participants signed an informed consent form before the survey was conducted. More details on the research methodology used to gather and analyze the KNHANES are available from the KNHANES website.Participants over the age of 18 years were identified for this study. A total of 10,649 individuals  were included as our final study population after excluding persons who never consumed alcohol.Baseline individual characteristics regarding gender, age, household income, education level, co-habitation, residential region, occupation, smoking, and self-rated stress level were collected for all cases. Age was categorized into five groups . Household income was classified into four groups: low, middle-low, middle-high, and high. Education level was categorized as follows: elementary school graduate and under, middle school graduate, high school graduate, and college graduate or post-graduate. Co-habitation referred to whether the individual lived with a spouse. With regard to residential region, participants were classified into living in Seoul, living in an urban area, and living in a rural area. Occupation was categorized as follows: white-collar jobs, blue-collar jobs, and unemployed (including student and housewife). Smoking status was categorized into nonsmoker with no past smoking experience, ex-smoker, and current smoker. Self-rated stress level was categorized as follows: very much, much, little, and almost none.Self-reported questionnaires were used to assess each participant’s alcohol related behaviors. For the age at first drink, participants were asked the age at which they first started drinking, not counting tastes or sips, which was classified into eight categories . Three indicators of the adult alcohol drinking patterns were used: The Alcohol Use Disorder Identification Test (AUDIT) score, average drinking frequency in past year, and typical drinking quantity per drinking day in past year. AUDIT is a 10-item screening instrument developed by the World Health Organization for the early detection of persons with harmful alcohol consumption behavior Statistical analyses were performed using SAS version 9.2  to take into account the complex sampling design with sampling weights of KNHANES and provide nationally representative estimates. Descriptive statistics including means, standard deviation, and frequency for estimates of the adult alcohol drinking patterns were calculated for men and women separately since there was no interaction found. Baseline characteristics of the study participants according to the alcohol drinking patterns were compared using the chi-square test. The gender-specific alcohol drinking patterns were compared using a two sample t-test for continuous variables and the chi-square test for categorical variables. The gender-specific effects of the age at first drink on adult alcohol drinking patterns were tested using the chi-square test. Multiple logistic regression analysis was used to find out the relationships between the age at first drink and the adult alcohol drinking patterns after adjusting for potential confounders. Odds ratios and 95% confidence intervals (CIs) were calculated to describe the association between the age at first drink and the drinking patterns for those with age 14 years and under at first drink and each age from 15 through 20 years relative to those with age 21 years or older at first drink, which was the reference group. The sample weights account for sampling variability and adjust the data for differential probability of selection of persons in KNHANES complex sample survey design.The characteristics of 10,649 individuals based on the alcohol drinking pattern are shown in Just over half (59%) of the respondents were men and 41% were women. The mean AUDIT score was significantly higher for the men than the women with a mean AUDIT of 10.9±7.1 for the men and 4.7±5.0 for the women respectively . Among m470  = 2.18, P  = 0.0347), average drinking frequency , and typical dinking quantity per drinking day .Odds ratios and 95% CIs from multiple logistic regression analysis revealed that relative to those who waited until age 21 years or older, those who started drinking at an earlier age were more likely to have ≥8 on the AUDIT, report average drinking ≥2–3 times/week, and consume more than 5–6 drinks/drinking day . After cThis study demonstrated that alcohol drinking patterns in regards to AUDIT scores, average drinking frequency, and typical drinking quantity on drinking day in later adulthood were associated with the age at first drink in Korean. Although several studies indicated that the age at first drink is associated with later hazardous alcohol consumption Age, co-habitation, occupation, smoking, and self-rated stress level were significantly related to the drinking patterns for men, whereas education, co-habitation, smoking, and self-rated stress level were significant factors for the drinking patterns of women. Overall, men were more likely to have higher AUDIT score and reported drinking more frequently and more daily consumed alcohol quantity than women. Regardless of gender, our results showed a significant inverse association between the age at first drink and the adult alcohol drinking patterns: persons who first started drinking at earlier age are more likely to have ≥8 on the AUDIT, report average drinking ≥2–3 times/week, and consume more than 5–6 drinks/drinking day, which means individuals with at-risk drinking level The results were in accordance with several evidences from previous studies. Both men and women experiencing binge drinking in adulthood most frequently had a drinking onset of age 14 or under, which was an association that rapidly declined after age 21 This study has several limitations that need to be taken into consideration. First, we could not fully exclude the effects of information bias because the measurement of alcohol drinking patterns along with the age at first drink was based on a self-reported questionnaire survey. However, there is an evidence that self-assessment of alcohol consumption is reliable In conclusion, the present findings in a representative Korean population demonstrate that the age at first drink is a predictor of adult alcohol drinking patterns in both genders although men report consuming more alcohol and spend more time drinking than women. Our findings suggest that delaying the initiation of drinking might be an appropriate goal for prevention efforts and that the present level for the legal age limit (18 years) for alcohol use is relevant; in some countries it is even higher. Prescott and Kendler


Plasmodium malariae trophozoite-infected red blood cell isolated from a Burmese patient suffering from quartan malaria (top). Of note, the P. malariae-infected cell (bottom left) is covered with dense ‘spike-like’ excrescences , which are morphologically distinct from the larger, more rounded ‘knob’ structures found on a Plasmodium falciparum-infected red cell  (bottom right). The ‘knobs’ on red cells containing mature asexual forms of P. falciparum assist the infected cells to bind/sequester to the vascular endothelium under shear flow conditions and thus avoid splenic clearance. The function of P. malariae spikes  is not known. The sample from which the P. malariae pictured was isolated  had the diagnosis confirmed by polymerase chain reaction. This picture is artificially coloured. The horizontal black scale bars represent 1 μm. The two lower images are identical in scale and orientation.This Atomic Force Microscope image shows the surface of a


Magnesium deficiency in pregnancy frequently occurs because of inadequate or low intake of magnesium. Magnesium deficiency during pregnancy can induce not only maternal and fetal nutritional problems, but also consequences that might last in offspring throughout life. Many epidemiological studies have disclosed that small for gestational age (SGA) is associated with an increased risk of insulin resistance in adult life. We reported that intracellular magnesium of cord blood platelets is lower in SGA groups than that in appropriate for gestational age groups, suggesting that intrauterine magnesium deficiency may result in SGA. Taken together, intrauterine magnesium deficiency in the fetus may lead to or at least program insulin resistance after birth. In this review, we propose that intrauterine magnesium deficiency may induce metabolic syndrome in later life. We discuss the potential contribution of aberrant magnesium regulation to SGA and to the pathogenesis of metabolic syndrome.  Magnesium (Mg) is an important cofactor for the enzymes that are involved in carbohydrate metabolism: an important role of Mg in insulin action has been reported , 2; low ecretion , 4. Furtecretion , 6. BaseIn addition, several studies have shown the association of size at birth or indices in poor fetal growth with later development of metabolic syndrome and insulin resistance . Hales eIn this review, we discuss the potential contribution of aberrant Mg regulation to SGA and to the pathogenesis of metabolic syndrome later in life.It is reported that the amount of maternal Mg intake is not only associated with pregnancy outcome but also with infant outcome . The mea2+]i is maintained by the function of a Na+/Mg2+ exchanger i) is lower in children with diabetes mellitus and in children who are obese [2+]i decreases before the poor reactivity to insulin occurs in platelets. From these findings, we hypothesize that [Mg2+]i is decreased earlier than when poor reactivity to insulin develops in platelets exposed to an insulin resistant environment. This suggests that low [Mg2+]i may be an intrinsic abnormality in infants with low birth weight [2+]i in cord blood platelets to birth weight [2+]i, but not plasma magnesium, is lower in SGA than in the appropriate for gestational age (AGA) groups . Basal [Mg2+]i significantly correlates with birth weight (P < .0001) as well as cord plasma leptin (P = .031) and IGF-1 (P < .001) [2+]i as well as leptin and IGF-1 reflects the extent of fetal growth. Also, [Mg2+]i significantly correlates with the quantitative insulin sensitivity check index (QUICKI)) (P < .001). Decreased [Mg2+]i in SGA might underlie the initial pathophysiological events that lead to insulin resistance.We have previously reported that intracellular magnesium ([Mgre obese . In the h weight . To testh weight . We foun < .001) . [Mg2+]i2+]i. For example, hyperglycemia may have an effect on Mg2+ transport and induce a decline of [Mg2+]i. Barbagallo et al. reported that responses to hyperglycemia in vitro were blunted in adult hypertensive subjects and that these responses were closely linked to basal [Mg2+]i levels [2+]i levels. In addition, we did not find any significant difference in plasma glucose levels between the SGA and AGA groups. Intrauterine glucose levels may have less of an effect on inducing SGA or low [Mg2+]i. As [Mg2+]i plays a promotive role in fetal growth, low [Mg2+]i may partly be responsible for SGA.Several factors are reported to affect [Mgi levels . In our 2+]i is an intrinsic abnormality seen in infants with low birth weight, it is considered that fetal Mg deficiency is an important determinant of insulin resistance in later life i may be a marker of early growth restriction, which may be of future diagnostic use as an early predictor of adult diseases. Low [Mg2+]i, which may represent the prenatal programming of insulin resistance, has lifelong effects on metabolic regulation. A biological interpretation of the association between birth size and risk of insulin-resistant diseases should emphasize the possible underlying roles of [Mg2+]i.Birth weight is only a crude index of early growth and indicates nothing about the success of a fetus in achieving its growth potential. [Mg


To investigate whether binge drinking pattern influences blood pressure independently from drinking volume or whether it modifies the effect of volume of drinking.We used cross-sectional data from population samples of 7559 men and 7471 women aged 45–69 years in 2002-05, not on antihypertensive medication, from Russia, Poland and Czech Republic. Annual alcohol intake, drinking frequency and binge drinking (≥100 g in men and ≥60 g in women in one session at least once a month) were estimated from graduated frequency questionnaire. Blood pressure was analysed as continuous variables (systolic and diastolic pressure) and a binary outcome (≥140/90 mm Hg).In men, annual alcohol intake and drinking frequency were strongly associated with blood pressure. The odds ratio of high blood pressure for binge drinking in men was 1.62 (95% CI 1.45–1.82) after controlling for age, country, body mass index, education and smoking; additional adjustment for annual alcohol intake reduced it to 1.20 (1.03–1.39). In women, the fully adjusted odds ratio of high blood pressure for binge drinking was 1.31 (1.05–1.63). Binge drinking did not modify the effect of annual alcohol intake. Consuming alcohol as wine, beer or spirits had similar effects.The results suggest that the independent long-term effect of binge drinking was modest, that binge drinking did not modify the effect of alcohol intake, and that different alcoholic beverages had similar effects on blood pressure. It has been long known that drinking alcohol is related to the risk of hypertension. Most studies reported a J-shaped (or a threshold based) association between alcohol and hypertension It has been proposed that in addition to the volume of drinking, the pattern of drinking is also important for cardiovascular risk Given the relatively high frequency of binge drinking in eastern Europe, and especially in Russia, with approximately one third of Russian men reporting binge drinking The study was approved by ethical committees at University College London (UK), the Jagiellonian University, Krakow (Poland), the National Institute of Public Health, Prague (Czech Republic) and the Institute of Internal Medicine, Novosibirsk (Russia); all participants gave written consent.We used cross-sectional data from the baseline survey for the Health, Alcohol and Psychosocial factors In Eastern Europe (HAPIEE) study, conducted in 2003–2005. Details on the study design and procedures have been reported elsewhere Blood pressure was measured by trained nurses according to standardized protocol, using Omron 5Mi sphygmomanometer. For each participant, three measurements in sitting position were recorded, the first after 5 minute rest and subsequent readings after 2 minute intervals. The means of the second and third measurements of systolic and diastolic BP were used in the analyses. Self-reported details on physician-diagnosed hypertension and its treatment were collected using standard health-related questionnaire. The binary variable of high blood pressure was defined as systolic BP≥140 and/or diastolic BP≥/90 mm Hg. Persons reporting treatment by antihypertensive medication were excluded.Alcohol consumption in the last year was ascertained by interviewer administered structured questionnaire. The reliability of the responses was assessed by investigating the proportion of abstainers and distribution of annual ethanol intake between observers, and data collected by interviewers with unusually high rates of underreporting were excluded from the analysis.The main alcohol indices analysed here were derived from the graduated frequency questionnaire (GFQ) In addition to assessing annual intake and drinking frequency, the GFQ data were also used to estimate the prevalence binge drinking. Binge drinking was defined as drinking 100 g (men) or 60 g (women) of ethanol in one session at least once a month. This cut off point in males is slightly higher than the 80 g Finally, we also categorized drinkers by beverage preference. The type of alcoholic beverage predominantly consumed was assessed using separate standard questions on consumption of particular types of alcoholic beverage during a typical week. Persons were classified into particular categories when the intake of ethanol of one type of beverage  was at least 75% of the total ethanol consumed. Participants not meeting these criteria were assumed to not to have a preference.2).Information on education and smoking was also collected by interviewer-administered questionnaire. For the purpose of this analysis we categorised education into 4 categories: primary or less, vocational, secondary, and university degree. We used 2 categories of smoking habit: non-smokers and current smokers. Participants' height and weight, measured without shoes and heavy outer garments using an electronic scale and mechanic stadiometer, were used to calculate body mass index , data from all countries were pooled. Since the results differed by sex, data on men and women were analysed separately.We used logistic and linear regression to assess the association between the prevalence of hypertension, and mean systolic and diastolic blood pressure, respectively, and alcohol. For each outcome, for each sex separately, we fitted three sets of models. First, we adjusted for age and country. Second, we also added education, smoking and body mass index. Finally, we have additionally included measures of annual alcohol intake and binge drinking simultaneously. Where appropriate, we also tested for linear trends by using the categorical independent variables as continuous variables.Interactions between annual intake of alcohol and binge drinking  were tested in stratified analyses and by regression models comparing likelihood ratios of models with and without interaction terms; we did this both including and excluding non-drinkers . Analyses were conducted using the SAS and Stata software.The characteristics of persons included in the analysis by country and sex are shown in There were considerable differences in the volume of alcohol consumption and style of drinking between the centres . The proDespite differences in drinking pattern between countries, the relations between ethanol consumption indices and hypertension were similar across the countries. For example, the odds ratios of high BP for men consuming ≥12 litres of ethanol per year, compared to non-drinkers, were 2.35 (95% CI 1.51–3.67) in the Czech Republic, 2.31 (1.73–3.06) in Russia and 3.14 (1.73–5.10) in Poland . Data from the 3 countries were therefore pooled  and 3. IIn women, the associations were generally weaker than in men . Age- anNext, we have examined the hypothesis that binge drinking modifies the effect of annual intake . In men,An alternative analysis of drinking pattern, stratifying drinkers into binge and non-binge drinkers, is shown in Beverage preference also did not modify the effect of drinking alcohol; after controlling for annual alcohol intake, the odds ratios of high BP (compared to non-drinkers) among drinkers preferring different drinks were very similar . SimilarThis study, in large Central and East European population samples with high levels of male binge drinking, found a small effect of binge drinking on blood pressure once the frequency and volume of drinking were taken into account, and there was no evidence that the effect of drinking is modified by binge drinking pattern. Our study confirms strong effects of conventional measures of alcohol consumption, such as the volume and frequency of drinking, and we found no evidence of a protective effect of moderate drinking.Several limitations of the study need to be considered when interpreting the results. The main issue is the cross-sectional design which may complicate the temporality. It is possible that persons with high BP reduce their drinking, leading to underestimation of an underlying association. However, this bias seems unlikely in our study; when the analyses were restricted to persons who were not aware of having high blood pressure, the results were virtually identical (not shown in tables).Second, persons taking antihypertensive medication were excluded in order to eliminate the confounding effect of the negative relation between undergoing treatment and the alcohol consumption. This may affect the generalizability of the results. However, in analyses of the full data, persons taking antihypertensive medication had lower alcohol consumption and lower blood pressure. When these subjects were included in the analyses, the associations between alcohol and blood pressure, after adjusting for medication, were essentially the same as the main results. Similarly, inclusion of data collected by 5 Krakow nurses, because they were deemed to be of low quality, did not affect the results.Third, self-reported measures of alcohol consumption are prone to underreporting and misclassification. In fact, when using additional variables not included in the main analyses, we found some evidence for under-reporting: non-drinkers and infrequent drinkers in the graduate frequency questionnaire (the main measure in the paper) reported some drinking when responding to a questions on typical weekly intake and in a food frequency questionnaire administered on a separate occasion. This under-reporting can plausibly explain the relatively high odds ratios among infrequent drinkers in the main analyses. In addition, underreporting may be more pronounced in women in Russia On the other hand, binge drinking, as a more visible way of drinking, may be less prone to misclassification than annual intake. If this is the case, the effect of binge drinking is underestimated to a lesser degree than the effect of volume or frequency of drinking; and this differential degree of misclassification, effectively leading a residual confounding Third, the lack of the effect of binge drinking may be due to the interval since last drinking occasion. While we had no data on the timing of the last drinking session, day of the week has been found to be associated with drinking on other studies Fourth, our measures of alcohol consumption covered the last year, and this classification may be affected by stopping or reducing drinking before the last 12 months. A question on stopping/reducing drinking in the past was available on our Russian sample, and stratifying the analyses by past consumption did not change the results. It is therefore unlikely that past drinking confounded our findings.Fifth, the study assessed long-term effects of binge drinking but it was unable to capture short-term effects. It has been suggested the some of the effect of ethanol on blood pressure are short term Finally, the response rate, although similar to many recent population studies, was relatively low. In epidemiological studies, non-responders tend to have higher levels of unhealthy behaviours and be less healthy . It is therefore possible that the levels of alcohol consumption and hypertension in the study samples were underestimated. However, it is unlikely that participation rate would introduce major bias in the estimates of the association between alcohol and blood pressure.This study also had a number of strengths. Perhaps the most important is the choice of study populations. Eastern European countries have a high alcohol consumption and, particularly in the countries of the former Soviet Union, high rates of binge drinking With respect to the conventional measures of alcohol consumption, our results confirm previous findings that alcohol intake and drinking frequency are associated with high blood pressure in an approximately linear fashion Binge drinking was the main focus of this study, because it has been previously linked with increased risk of hypertension and cardiovascular risk in general. We found a relatively modest effect of binge drinking on blood pressure after controlling for the volume of drinking. We used several alternative ways to analyse the possible interaction between alcohol intake and binge drinking but our data do not support the hypothesis that drinking pattern modified the effect of alcohol intake. The fact that associations between alcohol and blood pressure were homogenous across participating countries also contradicts the hypothesis that drinking pattern modifies the effect of ethanol – given the high prevalence of binge drinking in Russia, one would expect stronger effects of a given alcohol intake on blood pressure in Russia; this was not the case.Current evidence on this subject is surprisingly sparse. The largest population-based study to date, the PRIME study, provided indirect evidence based on ecological comparison of day of week variation in BP between Northern Ireland and France Several studies reported a positive association between blood pressure and drinking without meals, another dimension of drinking pattern Our findings may have implications for both public health and medical practice. Firstly, although moderate alcohol consumption is associated with slightly lower risk of coronary heart disease, our (and others') results demonstrate a linear dose-response association between ethanol and blood pressure; this should lead to more cautious recommended levels of alcohol consumption. Secondly, while binge drinking has a number of negative consequences on health, the evidence that it has a clinically meaningful long term effect on blood pressure, once total alcohol intake is taken into account, is not supported by our results. And finally, many people view wine as more healthy type of alcohol but our results corroborate earlier findings that blood pressure is increased by all types of alcoholic beverages to a similar extent.