Clinical effectiveness of intense pulsed light therapy for solar lentigines of the hands

Intense pulsed light (IPL) treatment, as a nonablative phototherapy, is known to improve various signs of facial photoaging skin, e.g., solar lentigines, fine wrinkles, and telangiectasias. The purpose of the present study was to investigate the efficacy and tolerability of IPL with a 515-nm filter in patients with solar lentigines on the back of hands. An open study was performed in 31 patients who were treated with a 1-month interval up to five times. Sixty-two percent of patients had more than 50% improvement and 23% had more than 75% improvement. No patients discontinued due to adverse effects, and no patients showed hyperpigmentation or scarring after the treatments. Phototherapy using this IPL source was effective and well tolerated in the patients, suggesting that this phototherapy may be an appropriate modality for the treatment of solar lentigines of the hands.     

Type‐dependent association between risk of cervical intraepithelial neoplasia and viral load of oncogenic human papillomavirus types other than types 16 and 18

Studies of the clinical relevance of human papillomavirus (HPV) DNA load have focused mainly on HPV16 and HPV18. Data on other oncogenic types are rare. Study subjects were women enrolled in the atypical squamous cells of undetermined significance (ASC‐US) and low‐grade squamous intraepithelial lesion (LSIL) triage study who had ≥1 of 11 non‐HPV16/18 oncogenic types detected during a 2‐year follow‐up at 6‐month intervals. Viral load measurements were performed on the first type‐specific HPV‐positive specimens. The association of cervical intraepithelial neoplasia grades 2–3 (CIN2/3) with type‐specific HPV DNA load was assessed with discrete‐time Cox regression. Overall, the increase in the cumulative risk of CIN2/3 per 1 unit increase in log₁₀‐transformed viral load was statistically significant for four types within species 9 including HPV31 (adjusted hazard ratio [HR _adjusted] = 1.32: 95% confidence interval [CI], 1.14–1.52), HPV35 (HR _adjusted = 1.47; 95% CI, 1.23–1.76), HPV52 (HR _adjusted = 1.14; 95% CI, 1.01–1.30) and HPV58 (HR _adjusted = 1.49; 95% CI, 1.23–1.82). The association was marginally significant for HPV33 (species 9) and HPV45 (species 7) and was not appreciable for other types. The per 1 log₁₀‐unit increase in viral load of a group of species 9 non‐HPV16 oncogenic types was statistically significantly associated with risk of CIN2/3 for women with a cytologic diagnosis of within normal limits, ASC‐US, or LSIL at the first HPV‐positive visit but not for those with high‐grade SIL. Findings suggest that the viral load‐associated risk of CIN2/3 is type‐dependent, and mainly restricted to the species of HPV types related to HPV16, which shares this association.     

Persistence of newly detected human papillomavirus type 31 infection,stratified by variant lineage

Variants of human papillomavirus (HPV) type 31 have been shown to be related both to risk of cervical lesions and racial composition of a population. It is largely undetermined whether variants differ in their likelihood of persistence. Study subjects were women who participated in the ASCUS‐LSIL Triage Study and who had a newly detected HPV31 infection during a two‐year follow‐up with six‐month intervals. HPV31 isolates were characterized by sequencing and assigned to one of three variant lineages. Loss of the newly detected HPV31 infection was detected in 76 (47.5%) of the 160 women (32/67 with A variants, 16/27 with B variants and 28/66 with C variants). The adjusted hazard ratio associating loss of the infection was 1.2 (95% CI, 0.7–2.1) for women with A variants and 2.1 (95% CI, 1.2–3.5) for women with B variants when compared with those with C variants. Infections with A and C variants were detected in 50 and 41 Caucasian women and in 15 and 23 African‐American women, respectively. The likelihood of clearance of the infection was significantly lower in African‐American women with C variants than in African‐American women with A variants (p = 0.05). There was no difference in the likelihood of clearance between A and C variants among Caucasian women. Our data indicated that infections with B variants were more likely to resolve than those with C variants. The difference in clearance of A vs. C variants in African‐Americans, but not in Caucasians, suggests a possibility of the race‐related influence in retaining the variant‐specific infection.     

Assessment of in vitro antiovulatory activities of nonsteroidal anti‐inflammatory drugs and comparison with in vivo reproductive toxicities of medaka (Oryzias latipes)

Nonsteroidal anti‐inflammatory drugs (NSAIDs) are widely used therapeutic agents; however, their pharmacological actions raise concerns about potential risks to the reproductive health of aquatic vertebrates. In the present study, a medaka ovulation assay was applied as an in vitro model to evaluate NSAID‐induced antiovulatory activity. We first tested five NSAIDs, including diclofenac sodium (DCF), ketoprofen (KP), salicylic acid (SA), mefenamic acid (MA), and acetylsalicylic acid (ASA) for their antiovulatory activities toward the follicles isolated from the ovaries of spawning females. Of all the chemicals tested, DCF had the highest antiovulatory activity, with the concentration that caused 50% inhibition (IC50) (101 µM). MA was the second most potent inhibitor following DCF, but KP, SA, or ASA had little inhibitory effect on the ovulation of the follicles. The in vitro antiovulatory activity of five NSAIDs showed good correlation with data published on the inhibitory activity on human COX‐2. Second, we selected DCF and SA as the most and least potent NSAIDs, respectively, and examined the effects on reproduction of intact fish in order to evaluate whether the ovulation assay was a reasonable predictor of potential reproductive effects in fish. Females exposed to DCF showed a concentration‐dependent decrease in the number of spawned eggs and an increment in the gonadosomatic index (GSI), possibly due to an anovulation in the females. In contrast, neither fecundity nor the GSI of females decreased at up to 20 mg/L of SA, at which acute lethality to medaka was induced. In conclusion, the medaka ovulation assay reflected the potency of NSAID‐induced antiovulatory activity and may thus serve as an in vitro model for the prediction of NSAID‐induced reproductive toxicity. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1710–1719, 2016.     

Age estimation by quantitative features of pubic symphysis using multidetector computed tomography

Macroscopic assessment of the pubic symphysis is commonly used for age estimation because its surface changes over time. However, postmortem computed tomography (PMCT), a method several forensic medical departments and institutes have begun to adopt, has the potential to simplify the information gathering process from the pelvic bone without requiring soft tissue removal. Some studies have previously evaluated the use of three-dimensional images of the pubic symphysis, but because of variance in the graphics processing among image analysis software packages, certain differences have been observed between these studies. Therefore, in this study, the PMCT findings of 199 subjects of known age and sex were retrospectively reviewed to examine the feasibility of age estimation using planar images of the pubic bones and soft tissue. The coronal and axial sectional images were observed at the center of the symphyseal surface, and the pubic bone length and thickness of the connective tissue of the pubic symphysis were measured at each slice. Our results revealed a significant positive correlation between the length of the pubic bone of the coronal section and age, suggesting that the use of a cutoff value for pubic bone length might be feasible for age estimations. In addition, the thickness of the connective tissue tended to narrow over time. Although the prediction interval range of planar images obtained by PMCT was major and is not usable in practice at this moment, it may still be a useful tool if used in conjunction with other findings obtained by PMCT.     

Consecutive tooth agenesis patterns in non-syndromic oligodontia

Agenesis of two or more consecutive adjacent permanent teeth (consecutive tooth agenesis, CTA) is a serious manifestation of oligodontia requiring long-term, multi-disciplinary treatment. Therefore, the present study investigated the characteristics of the CTA pattern in orthodontic patients with non-syndromic oligodontia. Using panoramic radiographs, the number of agenetic permanent teeth excluding third molars in non-syndromic orthodontic patients was evaluated, and patients with six or more agenetic teeth (oligodontia group, n?=?97) and with one to five agenetic teeth (hypodontia group, n?=?107) were selected. The numbers of CTA including third molars in each quadrant and in each patient were compared between the groups. Each quadrant with CTA of patients was categorized into one of the following four types: (I) involves anterior teeth only; (II) involves posterior teeth only; (IIIA) includes anterior and posterior teeth; and (IIIB) separate in the anterior and posterior teeth. CTA in at least one quadrant was found in 91.8 and 4.7% of patients in the oligodontia and hypodontia groups, respectively. The highest frequency CTA patterns included agenesis of the first and second premolars and of the second and third molars in the oligodontia and hypodontia groups, respectively. In the oligodontia group, type IIIA was significantly more frequent in the maxillary than in the mandibular quadrant. Most oligodontia patients who visit orthodontic clinics have CTA. A rare but severe CTA pattern that continues from the anterior to posterior segments is more frequent in the maxillary than in the mandibular quadrant.

     

Vα24-invariant NKT cells mediate antitumor activity via killing of tumor-associated macrophages

Tumor infiltration with Vα24-invariant NKT cells (NKTs) associates with favorable outcome in neuroblastoma and other cancers. Although NKTs can be directly cytotoxic against CD1d⁺ cells, the majority of human tumors are CD1d^–. Therefore, the role of NKTs in cancer remains largely unknown. Here, we demonstrate that CD68⁺ tumor-associated monocytes/macrophages (TAMs) represented the majority of CD1d-expressing cells in primary human neuroblastomas. TAMs stimulated neuroblastoma growth in human cell lines and their xenografts in NOD/SCID mice via IL-6 production. Indeed, TAMs produced IL-6 in primary tumors and in the BM of patients with metastatic neuroblastoma. Gene expression analysis using TaqMan low-density arrays of 129 primary human neuroblastomas without MYCN amplification revealed that high-level expression of TAM-specific genes (CD14, CD16, IL6, IL6R, and TGFB1) was associated with poor 5-year event-free survival. While NKTs were not cytotoxic against neuroblastoma cells, they effectively killed monocytes pulsed with tumor cell lysate. The killing of monocytes was CD1d restricted because it was inhibited by a CD1d-specific mAb. Cotransfer of human monocytes and NKTs to tumor-bearing NOD/SCID mice decreased monocyte number at the tumor site and suppressed tumor growth compared with mice transferred with monocytes alone. Thus, killing of TAMs reveals what we believe to be a novel mechanism of NKT antitumor activity that relates to the disease outcome.