Phenotypic and molecular analysis of dominant occurring antibiotic active-producing Streptomyces soil flora in Northern Jordan.

This investigation aimed to determine the relatedness of dominant occurring soil Streptomyces spp. in Northern Jordan based on their RAPD-PCR fingerprints, and to compare RAPD technique with the conventional phenotypic characterization of Streptomyces isolates. Fifty-eight white and gray color-bearing aerial mycelia antibiotic active-producing Streptomyces soil isolates along with three reference strains were genetically analyzed by RAPD-PCR. Polymorphisms between the isolates showed 1 to 10 bands per isolate and ranged from 200 to 3200 bp in size. Results revealed one common band of ~600 bp shared by ~85% of the isolates, and the observation of bands specific to some reference strains and some soil isolates. When RAPD patterns were analyzed with the UPGMA, results revealed clustering the tested isolates into two equal main super clusters (50% each). Super cluster I appeared to be homogenous and include the three reference strains. However, super cluster II was heterogeneous and but not including any of the reference strains. The association of the antibiotic activity of the dominant white and gray aerial mycelium-bearing Streptomyces isolates to RAPD clustering is reported for the first time, and the RAPD-PCR fingerprints generated here deserve to be cloned, characterized and sequenced in future as Streptomyces species-specific DNA markers. The more random primers used in the analysis may add to RAPD technique a cost-effective, fast, precise result, and less labor work solution for analyzing the similarities and differences among the Streptomyces isolates.

[A multidimensional v-shaped distalizing osteotomy of the tibial tuberosity with a proximal buttress ("coffin-shaped" osteotomy)]. / Die multiplanare v-förmige distalisierende Tuberositasosteotomie mit proximalem Widerlager ("sargförmige" Osteotomie).

The aim of the intervention presented is a distalization of the tibial tuberosity. It is indicated in patients with symptomatic patella alta, i.e. patients with instability of the patella. It facilitates a V-shaped osteotomy. The bone gained during distalization is used as a proximal buttress. This leads to an improved mediolateral and proximal stability. The bony surface area is increased, which improves bony healing. There were no secondary dislocations in the patient group of 10 patients treated by the surgeon.

A Review of ß-Lactam-Associated Neutropenia and Implications for Cross-reactivity.

OBJECTIVE: To review the incidence, management, and current understanding of the pathophysiology of ß-lactam-induced neutropenia and to critically evaluate the practicality and safety of direct substitution to an alternative ß-lactam in the setting of this reaction. DATA SOURCES: A literature analysis using the PubMed and Ovid search engines (July 1968 to October 2020) was performed using the search terms neutropenia, leukopenia, ß-lactam, nonchemotherapy, agranulocytosis, and G-CSF (granulocyte colony-stimulating factor). STUDY SELECTION AND DATA EXTRACTION: The included English-language studies evaluated the incidence, mechanism, and/or management of ß-lactam-induced neutropenia in pediatric or adult patients. DATA SYNTHESIS: Drug-induced neutropenia is a well-documented adverse reaction of ß-lactam antibiotics, with an incidence of approximately 10% following at least 2 weeks of intravenous therapy. However, multiple gaps in knowledge remain in the mechanism of pathophysiology and optimal management of this reaction. Both direct toxic and immune-mediated mechanisms have been implicated. Although the cornerstone of management includes cessation of the offending agent, controversy exists on the appropriateness of direct substitution or future use of an alternative ß-lactam. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Given the frequency of use and superiority of ß-lactams over alternative therapy for several infectious disease states, practical recommendations are needed on the management and safe use of ß-lactams following ß-lactam-induced neutropenia. CONCLUSION: Future use of ß-lactams with differing R1 side chains, particularly those from a separate class, should not be deemed contraindicated following ß-lactam-induced neutropenia and may be considered when indicated, with close laboratory monitoring.

Effects of insulin and metformin on fetal kidney development of streptozotocin-induced gestational diabetic albino rats.

Gestational diabetes mellitus is one of common medical complications of pregnancy. Hyperglycemia in utero impairs renal development and produces renal anomalies. Metformin has antioxidant properties and better glycemic control. Aim: assessment insulin and metformin effects on renal development of streptozotocin-induced gestational diabetic albino rats. Sixty virgin female albino rats were used. Once pregnancy confirmed, animals were randomly assigned into control, metformin, diabetic, diabetic plus insulin, diabetic plus metformin and diabetic plus insulin and metformin treated groups. Rats were sacrificed on the 20th day of gestation; fetuses were extracted and weighted. Fetal kidneys were extracted prepared for light, morphometric and electron microscopic examination. Diabetic followed by diabetic plus metformin treated groups revealed retardation of glomerular development in the cortical and Juxtaglomerular zones with a significant increase in the early immature glomerular stages and immature to mature glomerular ratio compared to other groups. Diabetic group also showed morphometric changes, shrunken and empty glomeruli, vacuolar degeneration and hemorrhage. Diabetic plus metformin group showed minimal improvement while diabetic plus insulin and diabetic plus insulin and metformin groups showed developmental, histopathological and morphometric improvement with best results in the combination group. Gestational diabetes mellitus (GDM) possess deleterious effects on fetal kidney development. Insulin improves the glycemic state and decreases GDM effects on fetal kidneys. Metformin produces mild protection while the combination of insulin and metformin produces the best glycemic control and protect fetal kidneys.

[Evaluation of primary tinnitus with fine puretone test and estimate of the technique].

Objective:To evaluate the relative factors of the severity and characteristics of primary tinnitus patients with fine puretone test(FPT) by three kinds of octaves, and to estimate the clinical application of this technique.Method:All subjects(n=90, ears=108), diagnosed with primary tinnitus, were recruited during July 2017 to February 2018 from the out-patients of Nanfang Hospital. In the prospective design, the patients were randomly divided into group 1/3 octave(n=30, ears=35), group 1/12 octave(n=30, ears=37) and group 1/24 octave(n=30, ears=36). Then tinnitus handicap inventory(THI), FPT, time and degree of residual inhibition(RI), time and degree of hyposensitization test, time attenuation test of masking(TATM) were used for evaluating the diseased and healthy ear performed separately.Result:Eighty-six patients were taken THI. The severity of tinnitus was no significant correlation with the gender,ear,sleep time and working time(P>0.05),but positive correlation with age(r=0.274, P=0.011) and duration of tinnitus(r=0.239, P=0.026). The selfassessment loudness score(SALS)(r=0.542,P=0.000) and the visual analogue score(VAS)(r=0.529, P=0.000) showed a moderate positive correlation. In the 1/24 octave, except for the TATM of the diseased ear group, the results of other groups were statistically different from the 1/3 octave(P<0.05), and much suitable than the 1/3 octave. Moreover, the results showed that the time of RI in the left and diseased ear group, the time of HT in the right, left and diseased ear group, the degree of HT in the right ear group were statistically different from the 1/12 octave(P<0.05) respectively, and much suitable than the 1/12 octave. The 1/12 octave was only statistically different from the 1/3 octave in TATM of the diseased ear group(P<0.05), and much suitable than the 1/3 octave.Conclusion:This study shows that gender, ear, sleep time, and working time had no significant effect on the severity of tinnitus, the age and duration of tinnitus have certain effects on the severity of tinnitus, the SALS, VAS score and the severity of tinnitus are moderately positively correlated. The 1/24 octave is significantly much suitable than the 1/3 octave and the 1/12 octave. And the technique of FPT is beneficial to improve the reliability and accuracy of the tinnitus evaluation.

Effects of insulin and metformin on fetal kidney development of streptozotocin-induced gestational diabetic albino rats / 대한해부학회지

Gestational diabetes mellitus is one of common medical complications of pregnancy. Hyperglycemia in utero impairs renal development and produces renal anomalies. Metformin has antioxidant properties and better glycemic control. Aim: assessment insulin and metformin effects on renal development of streptozotocin-induced gestational diabetic albino rats. Sixty virgin female albino rats were used. Once pregnancy confirmed, animals were randomly assigned into control, metformin, diabetic, diabetic plus insulin, diabetic plus metformin and diabetic plus insulin and metformin treated groups. Rats were sacrificed on the 20th day of gestation; fetuses were extracted and weighted. Fetal kidneys were extracted prepared for light, morphometric and electron microscopic examination. Diabetic followed by diabetic plus metformin treated groups revealed retardation of glomerular development in the cortical and Juxtaglomerular zones with a significant increase in the early immature glomerular stages and immature to mature glomerular ratio compared to other groups. Diabetic group also showed morphometric changes, shrunken and empty glomeruli, vacuolar degeneration and hemorrhage. Diabetic plus metformin group showed minimal improvement while diabetic plus insulin and diabetic plus insulin and metformin groups showed developmental, histopathological and morphometric improvement with best results in the combination group. Gestational diabetes mellitus (GDM) possess deleterious effects on fetal kidney development. Insulin improves the glycemic state and decreases GDM effects on fetal kidneys. Metformin produces mild protection while the combination of insulin and metformin produces the best glycemic control and protect fetal kidneys.

[Application of technique of HRCT and multipliate plane reconstruction in analysis of image features of superior semicircular canal dehiscence].

Objective: Application of technique of high resolution CT (HRCT) and multipliate plane reconstruction, analyzed the image features of suspicious superior semicircular canal dehiscence (SSCD) to improve the understanding of the SSCD.Method:From January 2016 to April 2017, a total of 230 adult patients who checked temporal bone HRCT were collected in this retrospective study, of which 160 cases (320 ears) of the non-SSCD, 73 cases were male (146 ears), 87 cases were female (174 ears), aged 18 to 70 years old; 70 cases (113 ears) were suspicious diagnosed with SSCD, 33 cases were male (55 ears), 37 cases were female (58 ears), and 18 to 71 years old. The thin section CT scan of the temporal bone translocation was performed on all subjects, then the CT post processing workstation was used for multipliate plane reconstruction (MPR), and the main rows of coronal and oblique sagittal image reconstruction was performed. To observe, measure and record the HRCT features and datas of the suspicious SSCD and non-SSCD, then analyze the collected data.Result:There were 160 cases (320 ears) in non-SSCD group, and the height of the superior semicircular canal was (6.43±0.51)mm, the outer tube diameter was (0.83±0.13)mm, the thickness of the tympanic cavity was (2.19±0.62)mm, the anteroposterior diameter of mastoid was (14.55±1.98)mm; There were 70 cases (113 ears) in the suspicious SSCD group, the above results were (6.42±0.60)mm, (0.85±0.16)mm, (1.62±0.55)mm, (13.24±1.97)mm, respectively. Statistical analysis showed that there were no significant difference in the height of the superior semicircular canal (P=0.94) and the outer tube diameter (P=0.64), There were significant differences in the thickness of the tympanic cavity (P=0.002) and the anteroposterior diameter of mastoid (P=0.004). There were 70 cases (113 ears) in group suspicious SSCD, the unilateral defect had 27 cases (27 ears), and bilateral defect had 43 cases (86 ears). The defect was located in the middle of the parietal wall in 48 ears, located in the anterior wall of 20 ears, located in the posterior wall of 32 ears, more than two defects in 13 ears; 7 ears were mastoid pneumatic type, 90 ears were mastoid sclerotic type, 16 ears were mastoid mixed type.Conclusion:The SSCD was more common in the sclerotic mastoid. The bilateral defect was common, mostly located in the middle of the parietal wall. The occurrence of the lesion is not related to the height and diameter of the superior semicircular canal, but may be related to the thinning of the whole temporal bone.

[Effect of melatonin on expression of Prestin protein in the inner ear of mice following radiotherapy].

Objective: To investigate the effect of melatonin on the expression of prestin protein in the inner ear of mice following a single dose radiation therapy, so as to provide the basis for the mechanism study of radiation induced inner ear injury and its prevention. Methods: Sixty 4-week-old male mice were randomly divided into six groups, including the control group (A group), 50 mg/kg MLT group (B group), 5 mg/kg MLT group (C group), 50 mg/kg MLT + radiotherapy group (D group), 5 mg/kg MLT+ radiotherapy group (E group), and 16 Gy radiotherapy group (F group). Each experimental group was randomly subdivided into two subgroups, which were killed to harvest the cochlea on the 3rd and 7th days following 16 Gy radiation. The specimens were used for immunostaining and Western blot to detect the expression of prestin protein. SPSS 19.0 software was used for statistical analysis. Results: Prestin protein mainly distributed in the lateral membrane above the outer hair cell nucleus. When compared with A, B and C group, the expression of prestin protein in the inner ear was significantly up-regulated in F group (P<0.05). However, D and E group reduced the abnormal expression of prestin following radiotherapy when compared with F group, the difference was statistically significant (P<0.05), and the effect of D group was more significant than E group (P<0.05). Conclusions: The prestin protein of cochlea is mainly distributed in the lateral membrane above the outer hair cell nucleus. Following the high-dose radiotherapy, the prestin expression is upregulated, and melatonin can control the abnormal expression of prestin protein induced by radiotherapy with dose dependent.

Evaluation of histological and biomechanical properties on engineered meniscus tissues using sonication decellularization.

Sonication decellularization treatment requires proper evaluations on its ability to decellularize meniscus tissue efficiently. This study was done to evaluate the histological and biomechanical properties within meniscus scaffolds. Van Gieson staining was done to evaluate the efficiency of cell removal in meniscus tissues. The consequences of treatment on viscoelastic properties are vital for scaffolds quality and were properly investigated. Picrosirius red and Safranin-O/Fast green staining was carried out to detect extracellular matrix materials (ECM). Sonication decellularization treatment has the ability to demonstrated complete nuclei removal compare to control samples as well as maintaining viscoelastic properties, namely stiffness, compression and residual force. Thus, sonication decellularization treatment had successfully produced and prepared a meniscus bioscaffold candidate in which its biomechanical strength is sustained through protection of ECM properties.

Evaluation of recellularization on decellularized aorta scaffolds engineered by ultrasonication treatment.

Aortic scaffolds prepared using sonication decellularization treatment has provided a successful medium for repopulation with vascular smooth muscle cells (VSMCs). The objective of this study is to explore the potential of tissue decellularization using ultrasonication treatment and its recellularization before implantation of the cell-seeded scaffolds into host. Aorta tissue samples are decellularized in 2% SDS with sonication for 10 hours and compared with the native tissues. The 4',6-diamidino-2-phenylindole (DAPI) staining was used to evaluate the decellularization and Hematoxylin-Eosin (H-E) staining was used to compare the VSMCs infiltrations onto the decellularized tissues at day-0 and day-6 after cell-seeding. The results histologically showed complete DNA removal from scaffolds after decellularization and subsequent recellularization resulted in successful VSMCs infiltration. Accordingly, the decellularized tissues treated with 2% SDS in sonication demonstrated successful VSMCs repopulation afterward and is speculated to have less toxicity and able to be effectively implanted into host.

Optimisation of breast cancer patients' follow-up - potential way to improve cancer care in transitional countries.

The aim of this analysis was to evaluate adherence of Croatian oncologists to follow-up criteria as suggested by the current national and international guidelines for women with breast cancer receiving adjuvant endocrine therapy. The use of clinical and diagnostic methods was documented in this prospective, non-interventional, multicenter study. A total of 438 post-menopausal patients receiving adjuvant endocrine treatment with non-steroidal aromatase inhibitors were included. Average annual frequency for each clinical and diagnostic method was calculated. Median adjuvant endocrine treatment duration before study recruitment was 10.5 months (interquartile 4.7-26.6). Patients were followed up for an average 23.5 ± 4.9 months. Average number of oncological visits was 5.3. Mammograms were performed at mean annual frequency of 0.7, chest radiographs at 0.5, abdominal ultrasounds at 0.9, breast ultrasounds at 1.2, complete blood counts and chemistry panels at 1.7, carcinoembryonic antigen at 0.8, cancer antigen 15-3 at 1.6, gynaecological examination at 0.3, and densitometry at mean annual frequency of 0.3. In conclusion, among post-menopausal women with breast cancer receiving adjuvant endocrine therapy in this study, more unnecessary and unproven follow-up procedures were done compared to the guidelines' recommendations.

Retrospective analysis of efficacy of trastuzumab in adjuvant treatment of HER 2 positive early breast cancer - single institution experience.

Addition of trastuzumab to chemotherapy is the cornerstone of adjuvant treatment of early HER2 positive breast cancer. Clinical trials and metaanalyses of adjuvant trastuzumab have shown significant reduction in risk of recurrence and death. Nevertheless, the real magnitude of the effect of any drug must be reevaluated in daily clinical conditions, due to the fact that daily clinical practice often differs from conditions in clinical trials. In order to measure the benefit of adding adjuvant trastuzumab in HER 2 positive early breast cancer treatment, we have performed retrospective analysis in a single institution on consecutive patients divided in 2 cohorts: one, treated in "pre - trastuzumab" and the other in "trastuzumab era". Between 2003 and 2012, 258 consecutive HER 2 positive patients with early breast cancer have been treated with adjuvant chemotherapy, 103 patients did not received trastuzumab (patients treated from 2003 till 2007), and 155 (patients treated from 2008 till 2012) received trastuzumab. Patients who received trastuzumab experienced significantly longer median disease-free survival (107 vs. 92 months, LR: 11.6, p <0.001); breast cancer-specific survival (130 vs. 117 months, LR: 10.7, p < 0.001) and median overall survival (123 vs. 108 months LR = 11.6, p < 0.001). The benefits of adding trastuzumab were independent of chemotherapy regimen and hormonal therapy. This retrospective analysis has shown a clear, statistically significant benefit of adjuvant trastuzumab in treatment of early, HER2 positive breast cancer in daily clinical practice, and confirmed the results of the registration clinical trials.

The effects of single-dose dexamethasone on inflammatory response and pain after uterine artery embolisation for symptomatic fibroids or adenomyosis: a randomised controlled study.

OBJECTIVE: To investigate the effects of single-dose intravenous dexamethasone on inflammatory responses, pain, nausea, and vomiting after uterine artery embolisation (UAE). DESIGN: Prospective, randomised, double-blind, and placebo-controlled study. SETTING: Tertiary-care University centre in Korea. POPULATION: Patients undergoing UAE for the treatment of symptomatic fibroids or adenomyosis. METHODS: Patients were randomised to receive either intravenous dexamethasone (10 mg; dexamethasone group) or normal saline (control group) 1 hour before UAE. Both groups received fentanyl-based intravenous patient-controlled analgesia (PCA) during the 24 hours after UAE. MAIN OUTCOME MEASURES: The primary outcomes were the inflammatory and stress responses measured by white blood cell count, neutrophil percentage, C-reactive protein (CRP), interleukin-6 (IL-6), and cortisol. Secondary outcomes were severity of pain and incidence of nausea and vomiting. RESULTS: Sixty-four patients were enrolled and 59 patients completed the study. CRP, IL-6, and cortisol were significantly lower in the dexamethasone group compared with the control group during the 24 hours after UAE. Although the cumulative dose of fentanyl and additional analgesics administered during the 24 hours after UAE were similar between the two groups, pain scores were significantly lower in the dexamethasone group from 12 hours after UAE, and the incidence of severe nausea and vomiting was lower in the dexamethasone group. CONCLUSIONS: The administration of single-dose intravenous dexamethasone as an adjunct to fentanyl-based intravenous PCA is effective in reducing inflammation and pain during the first 24 hours after UAE. TWEETABLE ABSTRACT: Dexamethasone is effective in reducing inflammation and pain after uterine artery embolisation.

Exome sequencing in single cells from the cerebrospinal fluid in multiple sclerosis.

BACKGROUND: Genome-wide association studies (GWAS) have identified over 100 germline variants that influence susceptibility to multiple sclerosis, most of which map within or near to genes with immunological function. However, the role of somatic mutations in multiple sclerosis has not been investigated. OBJECTIVE: The objective of this paper is to explore the role that somatic mutations might play in the development of multiple sclerosis. METHODS: We exome-sequenced in total 21 individual CD4+ lymphocytes isolated from cerebrospinal fluid of two patients. In addition we sequenced DNA from the patients' peripheral blood to serve as germline reference. RESULTS: In comparison with the respective germline sequence, each cell differed at an average of 1784 positions, but as anticipated subsequent analysis confirms that most, if not all, of these potential mutations are likely to represent artefacts generated during the amplification of a single genome and/or by sequencing. Fifty-six of the potential mutations were predicted to have likely functional effects on genes that have previously been implicated by GWAS, including three in the CD6 gene. CONCLUSION: More robust methods applied to larger numbers of cells will be needed to define the role of somatic mutations.

Is the reciprocating movement per se able to improve the cyclic fatigue resistance of instruments?

AIM: To compare cyclic fatigue resistance of two geometrically similar nickel-titanium instruments, used in conditions similar to clinical use in reciprocating and continuous rotary motion. METHODOLOGY: Four groups of eighteen instruments each, Reciproc(®) files sizes ISO 25 and 40 (R25 and R40) and Mtwo(®) files sizes ISO 25 and 40 (M25 and M40), were tested in reciprocating and continuous rotary motion, employing a novel experiment device. An artificial root canal (diameter, 1.4 mm; angle of curvature, 60 °; and curvature radius, 5 mm) was milled into a stainless steel block. To simulate clinical conditions, instead of rotating the file in static position, the set-up was designed to produce a continuous up-and-down pecking motion along the vertical axis of the instrument. Time to fracture (TTF) and push-pull cycles (PPC) were recorded, the number of cycles to fracture (NCF) was determined, and fractured instrument surfaces were examined under a scanning electron microscope (SEM). RESULTS: Mean time to fracture was 34.44 ± 8.58 min for R25 in reciprocation motion, 35.77 ± 4.82 min for R40 in reciprocation motion, 12.15 ± 1.74 min for M25 in continuous rotary motion and 13.27 ± 2.02 min for M40 in continuous rotary motion, whereas 28.52 ± 3.27 min for R25 in continuous rotary motion, 23.87 ± 1.52 min for R40 in continuous rotary motion, 31.07 ± 1.79 min for M25 in reciprocation motion and 31.08 ± 3.26 min for M40 in reciprocation motion. There was a significant difference (P < 0.0001) for the cyclic fatigue resistance between the reciprocation motion and the continuous rotary motion groups. Reciproc(®) files in reciprocating movement had a significantly higher NCF than Mtwo(®) files, when used in continuous rotation. The highest resistance to failure was shown by Reciproc(®) files in reciprocation movement, followed by Mtwo(®) files in reciprocation and Reciproc(®) files in continuous motion. Mtwo(®) files in continuous rotary movement had the least resistance. SEM analysis of the fracture surface confirmed typical features of cyclic fatigue failure. CONCLUSION: Reciprocating movement increased the cyclic fatigue resistance of NiTi instruments.

Genetic burden in multiple sclerosis families.

A previous study using cumulative genetic risk estimations in multiple sclerosis (MS) successfully tracked the aggregation of susceptibility variants in multi-case and single-case families. It used a limited description of susceptibility loci available at the time (17 loci). Even though the full roster of MS risk genes remains unavailable, we estimated the genetic burden in MS families and assess its disease predictive power using up to 64 single-nucleotide polymorphism (SNP) markers according to the most recent literature. A total of 708 controls, 3251 MS patients and their relatives, as well as 117 twin pairs were genotyped. We validated the increased aggregation of genetic burden in multi-case compared with single-case families (P=4.14e-03) and confirm that these data offer little opportunity to accurately predict MS, even within sibships (area under receiver operating characteristic (AUROC)=0.59 (0.55, 0.53)). Our results also suggest that the primary progressive and relapsing-type forms of MS share a common genetic architecture (P=0.368; difference being limited to that corresponding to ± 2 typical MS-associated SNPs). We have confirmed the properties of individual genetic risk score in MS. Comparing with previous reference point for MS genetics (17 SNPs), we underlined the corrective consequences of the integration of the new findings from GWAS and meta-analysis.

Interaction between the BDNF gene Val/66/Met polymorphism and morning cortisol levels as a predictor of depression in adult women.

BACKGROUND: Common genetic variants, such as the brain-derived neurotrophic factor (BDNF) Val/66/Met polymorphism (rs6265), are known to interact with environmental factors such as early adversity to increase the risk of subsequent major depression. Much less is known about how they interact with individual differences in cortisol, although these also represent a risk for major depression. AIMS: To determine whether this BDNF variant moderated the risk represented by higher levels of morning salivary cortisol in adult women. METHOD: We recruited 279 premenopausal women who were at high risk of major depressive disorder because of either negative self-evaluation, unsupportive core relationship or chronic subclinical symptoms of depression or anxiety. Morning salivary cortisol was measured daily for up to 10 days at entry. Participants were followed up for about 12 months by telephone calls at 3-4 monthly intervals. Major depression and severe life events were assessed through interviews at baseline and follow-up; DNA was obtained from the saliva. RESULTS: There were 53 onsets (19%) of depressive episodes during follow-up. There was a significant U-shaped relationship between adjusted morning cortisol levels at baseline and the probability of depression onset during follow-up. In total, 51% experienced at least one severe life event/difficulty, and this strongly predicted subsequent onsets of depressive episodes. The BDNF Val/66/Met genotype was not directly associated with onsets of depression or with cortisol levels, but there was significant interaction between Val/66/Met and cortisol: the association between baseline cortisol and depression was limited to those with the Val/66/Val variant. There was no interaction between life events and either this BDNF polymorphism or cortisol levels. CONCLUSIONS: Morning salivary cortisol interacts with the BDNF Val/66/Met polymorphism in predicting new depressive episodes. This paper adds to the evidence that single gene polymorphisms interact with endogenous factors to predict depression.

Lapatinib in the treatment of HER-2 overexpressing breast cancer.

Lapatinib is the only clinically available agent for the treatment of patients with human epidermal growth factor receptor-2 (HER-2) positive tumors that have progressed on treatment with trastuzumab, taxanes and anthracyclines. Moreover, when given with letrozole in postmenopausal patients with estrogen receptor (ER) and HER-2 positive disease it induces clinically meaningful benefit. Recently presented neoadjuvant data suggests an important place for the combination of trastuzumab and lapatinib in the therapy of early HER-2 positive breast cancer. This article reviews the current status and future perspectives of lapatinib.