Is fecundability associated with month of birth? An analysis of 19th and early 20th century family reconstitution data from The Netherlands

The relationship between fecundability and month of birth was investigated in a cohort of 1526 women who married between 1802 and 1929, using only women whose first marriage occurred before the age of 35 years. On the basis of their time to pregnancy (TTP, calculated as time between wedding and first birth minus gestational length), women were categorized into two groups: fecunds (TTP up to 12 months or prenuptial conceptions, n = 1348) and subfecunds (TTP >18 months, n = 118). By use of logistic regression, cosinor functions with a period of 1 year or 6 months and variable shift and amplitude were fitted through the monthly odds of subfecunds versus fecunds. The best fitting curve was unimodal, with a zenith in September (P = 0.13 for H0: no differences). Exclusion of childless women (n = 36, minimum follow-up 5 years) from the subfecunds led to a similar curve (P < 0.01), while childless women, as compared with fecunds, showed a birth distribution that was best represented with a bimodal curve with zeniths in January and July (P = 0.06). This study provides evidence for the existence of differences in fecundability by month of birth. The cause of this relationship is unclear, but may lie in a melatonin-dependent circannual variability of the quality of the oocyte.      

Human Y chromosome azoospermia factors (AZF) mapped to different subregions in Yq11

In a large collaborative screening project, 370 men with idiopathic azoospermia or severe oligozoospermia were analysed for deletions of 76 DNA loci in Yq11. In 12 individuals, we observed de novo microdeletions involving several DNA loci, while an additional patient had an inherited deletion. They were mapped to three different subregions in Yq11. One subregion coincides to the AZF region defined recently in distal Yq11. The second and third subregion were mapped proximal to it, in proximal and middle Yq11, respectively. The different deletions observed were not overlapping but the extension of the deleted Y DNA in each subregion was similar in each patient analysed. In testis tissue sections, disruption of spermatogenesis was shown to be at the same phase when the microdeletion occurred in the same Yq11 subregion but at a different phase when the microdeletion occurred in a different Yq11 subregion. Therefore, we propose the presence of not one but three spermatogenesis loci in Yq11 and that each locus is active during a different phase of male germ cell development. As the most severe phenotype after deletion of each locus is azoospermia, we designated them as: AZFa, AZFb and AZFc. Their probable phase of function in human spermatogenesis and candidate genes involved will be discussed.      

Interaction between vestibulo-spinal and corticospinal systems: a combined caloric and transcranial magnetic stimulation study

We investigated the interaction between vestibular and corticospinal stimuli in 8 healthy volunteers. Vestibular stimulation was induced with unilateral ear caloric irrigation (30°C) with subjects supine. Single transcranial magnetic stimulation (TMS) pulses were delivered (double-cone coil, intensities 60–75% maximal output) every 10–20 s during vestibular activation and during baseline. Bilateral surface electromyography (EMG) from splenius capitis, sternocleidomastoid (SCM), obliquus externus abdominis, vastus lateralis, biceps femoris (BF), tibialis anterior and peroneus longus was obtained. During whole-body maximal rotatory voluntary isometric contraction (MRVC), only SCM and BF displayed EMG activation/inhibition patterns indicating axial rotatory action. TMS-induced motor evoked potentials (MEPs) after caloric irrigation revealed that only SCM showed consistent vestibular-mediated excitation/inhibition responses, i.e. an increase in MEP area contralateral to the irrigation and a decrease in MEP area ipsilaterally (+12.7 and −6.3% of the MRVC, respectively). A putative head turn induced by this SCM activity pattern would be in the same direction of the slow-phase eye movement. EMG in the 100 ms preceding TMS showed muscle tone values of approximately 10% of MRVC. After caloric irrigation, these values increased by ca. 2% for all muscles bilaterally and hence cannot explain the direction-specific SCM MEP changes. Thus, SCM MEPs show caloric-induced amplitude modulation indicating that SCM is under both horizontal semicircular canal and corticospinal control. This vestibular modulation of corticospinal SCM control likely occurs at cortical levels. The direction of the MEP modulation indicates a directional coupling between vestibularly induced head and eye movements.     

CT‐guided aspiration cytology of advanced silicosis and confirmation of the deposited zeolite nano particles through X ray diffraction: A novel approach

Silicosis is a common occupational lung disease, resulting in fibrotic nodular lesions in the upper lobes of the lung parenchyma. Most of the pneumoconioses are diagnosed on the basis of relevant history and clinico‐radiological correlation. Image‐guided aspiration cytology appears to be poorly yielding and is not usually considered as a diagnostic modality. However, silicosis may sometimes offer a diagnostic challenge because of its radiological resemblance and clinical overlap with pulmonary tuberculosis and neoplastic lesions. We present a unique situation where image‐guided fine needle aspiration cytology (FNAC) has been advised on the basis of nodular upper lobe opacities. The cytology smears revealed hypocellular granular material, while phase contrast and polarized light microscopy highlighted crystalline particles. History of silica dust exposure long back was available after the cytological evaluation, suggesting the diagnosis of pulmonary silicosis. X ray diffraction (XRD) crystallography was also possible on cytology smears, confirming zeolite nano particles of size as small as 40 ? 50 nm as the concerned agent for the first time. Cytological evaluation by phase contrast and polarized light microscopy may be useful for the confirmation of silicosis, supplemented by clinical history and radiological evaluation. XRD on smears may help in determination of chemical nature and particle size. Diagn. Cytopathol. 2016;44:246–249. © 2015 Wiley Periodicals, Inc.     

Evaluation of a scoring system for predicting lymph node malignancy in ultrasound guided fine needle aspiration practice

Ultrasound‐guided fine needle aspiration (USG‐FNA) has enabled cytopathologists to accurately diagnose smaller or non‐palpable lymph nodes (LN) on a regular basis. Pre‐FNA clinical and ultrasonographic factors, such as a patient's age, ratio of short to long axis diameter (S/L ratio), internal echogenicity, and the vascular pattern of a LN, are reported to be able to predict the benign or malignant nature of a LN. This study is designed to test the formula “0.06 × (age) + 4.76 × (S/L ratio) + 2.15 × (internal echo) + 1.80 × (vascular pattern)” generated from the study of Liao et al. as a scoring system for predicting LN malignancy in a cytopathologist operated USG‐FNA practice. Eighty‐three reports of USG‐FNA of LNs issued between 7/1/2008 and 4/28/2010 were reviewed. Patient's age, S/L ratio, internal echo, and vascular pattern were used to generate scores based on the aforementioned formula. A score of seven was used as a cutoff for predicting benign (<7) and malignant (>7) LNs. FNA cytology diagnosis, flow cytometric analysis as well as subsequent surgical diagnosis in some cases served as gold standard for statistical analysis. Among 46 USG‐FNA of LNs with scores > 7, 38 were malignant and eight were benign. All 37 USG‐FNA of LNs with scores < 7 were proven to be benign. The scoring system achieved 100% sensitivity, 82% specificity, 83% positive predictive value, 100% negative predictive value, and 90% accuracy. Further study of the eight “false‐positive” cases revealed that three of them (37.5%) were found to be malignant in follow‐up FNA and/or surgical biopsy. This scoring system may serve as a complementary tool in determining how aggressive a FNA procedure should be performed, how a FNA sample of LN should be triaged for ancillary study, and how closely a patient with lymphadenopathy should be followed up. Diagn. Cytopathol. 2013;41:1100–1106. © 2011 Wiley Periodicals, Inc.     

Epidemiological Approach to Identifying Genetic Predispositions for Atypical Hemolytic Uremic Syndrome

Atypical hemolytic uremic syndrome (aHUS) is caused by several susceptibility genes. A registry including analyses of susceptibility genes, familial occurrence and genotype-phenotype correlation should provide classification insights.
Registry data of 187 unrelated index patients included age at onset, gender, family history, relapse of aHUS and potentially triggering conditions. Mutation analyses were performed in the genes CFH , CD46 and CFI and in the six potential susceptibility genes, FHR1 to FHR5 and C4BP .
Germline mutations were identified in 17% of the index cases; 12% in CFH , 3% in CD46 and 2% in CFI . Twenty-nine patients had heterozygous mutations and one each had a homozygous and compound heterozygous mutation. Mutations were not found in the genes FHR1-5 and C4BP . In 40% of the patients with familial HUS a mutation was found. Penetrance by age 45 was 50% among carriers of any mutation including results of relatives of mutation-positive index cases. The only risk factor for a mutation was family history of HUS (p = 0.02).
P enetrance of aHUS in carriers of mutations is not complete. Occurrence of homo- and heterozygous mutations in the same gene suggests that the number of necessary DNA variants remains unclear. Among clinical information only familial occurrence predicts a mutation.