Nuclear Pores Promote Lethal Prostate Cancer by Increasing POM121-Driven E2F1, MYC, and AR Nuclear Import.

Nuclear pore complexes (NPCs) regulate nuclear-cytoplasmic transport, transcription, and genome integrity in eukaryotic cells. However, their functional roles in cancer remain poorly understood. We interrogated the evolutionary transcriptomic landscape of NPC components, nucleoporins (Nups), from primary to advanced metastatic human prostate cancer (PC). Focused loss-of-function genetic screen of top-upregulated Nups in aggressive PC models identified POM121 as a key contributor to PC aggressiveness. Mechanistically, POM121 promoted PC progression by enhancing importin-dependent nuclear transport of key oncogenic (E2F1, MYC) and PC-specific (AR-GATA2) transcription factors, uncovering a pharmacologically targetable axis that, when inhibited, decreased tumor growth, restored standard therapy efficacy, and improved survival in patient-derived pre-clinical models. Our studies molecularly establish a role of NPCs in PC progression and give a rationale for NPC-regulated nuclear import targeting as a therapeutic strategy for lethal PC. These findings may have implications for understanding how NPC deregulation contributes to the pathogenesis of other tumor types.

MANAGEMENT OF LARGE FULL-THICKNESS MACULAR HOLES: Long-Term Outcomes of Internal Limiting Membrane Flaps and Internal Limiting Membrane Peels.

BACKGROUND/PURPOSE: To determine and compare the efficacy of a surgical internal limiting membrane (ILM) flap technique with the traditional ILM peel on long-term visual and anatomical outcomes for large (>400 µm) full-thickness macular holes. METHODS: From October 2016 to July 2022, patients undergoing initial full-thickness macular hole repair with the ILM flap or ILM peel technique were reviewed. Final outcomes were recorded and based on size in microns: 401 to 800, 801 to 1,200, and >1,200. RESULTS: Patients treated with ILM flap (n = 52, 94.2% closure rate) or ILM peel (n = 407, 93.6% closure rate) were followed with a mean follow-up time of 15.0 ± 10.2 and 20.0 ± 13.4 months, respectively. Success rates for ILM flaps and ILM peels were compared for full-thickness macular holes of 401 to 800 (100%, 95.8%, P = 0.39), 801 to 1,200 (95%, 93%, P = 0.74), and >1,200 (86.7%, 86.7%, P = 1.0) µm. Mean best-recorded logarithm of the minimal angle of resolution visual acuity for ILM flaps and ILM peels, respectively, was 1.02 ± 0.46 and 0.87 ± 0.47 preoperatively, with follow-up acuity of 0.48 ± 0.32 (P < 0.03) and 0.39 ± 0.42 (P < 0.01) at Year 3. CONCLUSION: Both techniques provide a similar anatomical closure rate and functional improvement in vision. Comparisons should be cautiously made based on difference in preoperative hole size.

Pain Scales: What Are They and What Do They Mean.

PURPOSE OF REVIEW: It is essential to have validated and reliable pain measurement tools that cover a wide range of areas and are tailored to individual patients to ensure effective pain management. The main objective of this review is to provide comprehensive information on commonly used pain scales and questionnaires, including their usefulness, intended purpose, applicability to different patient populations, and associated advantages and disadvantages. RECENT FINDINGS: Acute pain questionnaires typically focus on measuring the severity of pain and the extent of relief achieved through interventions. Chronic pain questionnaires evaluate additional aspects such as pain-related functional limitations, psychological distress, and psychological well-being. The selection of an appropriate pain scale depends on the specific assessment objectives. Additionally, each pain scale has its strengths and limitations. Understanding the differences among these pain scales is essential for selecting the most appropriate tool tailored to individual patient needs in different settings. CONCLUSION: Medical professionals encounter challenges in accurately assessing pain. Physicians must be familiar with the different pain scales and their applicability to specific patient population.

The Impact of Smoking on the Development and Severity of Chronic Pain.

PURPOSE OF REVIEW: The purpose of this review is to examine the impact of smoking and its role on the development of chronic pain and provide a critical review of recent literature. RECENT FINDINGS: Recent studies demonstrate the bidirectional and dependent relationship between smoking and chronic pain. Those who are in pain have a more difficult time in the cessation of smoking as well as an increased sensitivity to pain during abstinence, lower confidence, and higher relapse rates. The fear of pain and the anxiety and depression that abstinence causes results in a grim outcome for long-term cessation. The dependent nature between chronic pain and smoking is affected by numerous variables. Providers should consider a multiprong approach to treating chronic pain and targeting smoking cessation treatment by providing motivational therapy, nicotine replacement, and medication therapies to prevent relapse, and providing those who are more likely to relapse with a higher level of care.

Regional anesthesia techniques for cardiac surgery: where are we?

PURPOSE OF REVIEW: Inadequate pain relief after cardiac surgery results in decreased patient experience and satisfaction, increased opioid consumption with its associated adverse consequences, and reduced efficiency metrics. To mitigate this, regional analgesic techniques are an increasingly important part of the perioperative cardiac anesthesia care plan. The purpose of this review is to compare current regional anesthesia techniques, and the relative evidence supporting their efficacy and safety in cardiac surgery. RECENT FINDINGS: Numerous novel plane blocks have been developed in recent years, with evidence of improved pain control after cardiac surgery. SUMMARY: The current data supports the use of a variety of different regional anesthesia techniques to reduce acute pain after cardiac surgery. However, future randomized trials are needed to quantify and compare the efficacy and safety of different regional techniques for pain control after cardiac surgery.

Targeted Retinal Photocoagulation for Diabetic Macular Edema with Peripheral Retinal Nonperfusion: Three-Year Randomized DAVE Trial.

PURPOSE: To evaluate the effect of targeted retinal photocoagulation (TRP) on visual and anatomic outcomes and treatment burden in eyes with diabetic macular edema (DME). DESIGN: Phase I/II prospective, randomized, controlled clinical trial. PARTICIPANTS: Forty eyes of 29 patients with center-involved macular edema secondary to diabetes mellitus. METHODS: Eyes with center-involved DME and Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) between 20/32 and 20/320 (Snellen equivalent) were randomized 1:1 to monotherapy with 0.3 mg ranibizumab (Lucentis, Genentech, South San Francisco, CA) or combination therapy with 0.3 mg ranibizumab and TRP guided by widefield fluorescein angiography. All eyes received 4 monthly ranibizumab injections followed by monthly examinations and pro re nata (PRN) re-treatment through 36 months. Targeted retinal photocoagulation was administered outside the macula to areas of retinal capillary nonperfusion plus a 1-disc area margin in the combination therapy arm at week 1, with re-treatment at months 6, 18, and 25, if indicated. MAIN OUTCOME MEASURES: Mean change in ETDRS BCVA from baseline and number of intravitreal injections administered. RESULTS: At baseline, mean age was 55 years, mean BCVA was 20/63 (Snellen equivalent), and mean central retinal subfield thickness (CRT) was 530 µm. Thirty-four eyes (85%) completed month 36, at which point mean BCVA improved 13.9 and 8.2 letters (P = 0.20) and mean CRT improved 302 and 152 µm (P = 0.03) in the monotherapy and combination therapy arms, respectively. The mean number of injections administered through month 36 was 24.4 (range, 10-34) and 27.1 (range, 12-36), with 73% (362/496) and 80% (433/538) of PRN injections administered (P = 0.004) in the monotherapy and combination therapy arms, respectively. Goldmann visual field isopter III-4e area decreased by 2% and 18% in the monotherapy and combination therapy arms, respectively (P = 0.30). CONCLUSIONS: In this 3-year randomized trial of 40 eyes with DME, there was no evidence that combination therapy with ranibizumab and TRP improved visual outcomes or reduced treatment burden compared with ranibizumab alone.

Cataract Surgery Outcomes in Uveitis: The Multicenter Uveitis Steroid Treatment Trial.

PURPOSE: To assess the visual outcomes of cataract surgery in eyes that received fluocinolone acetonide implant or systemic therapy with oral corticosteroids and immunosuppression during the Multicenter Uveitis Steroid Treatment (MUST) Trial. DESIGN: Nested prospective cohort study of patients enrolled in a randomized clinical trial. PARTICIPANTS: Patients that underwent cataract surgery during the first 2 years of follow-up in the MUST Trial. METHODS: Visual outcomes of cataract surgery were evaluated 3, 6, and 9 months after surgery using logarithmic visual acuity charts. Change in visual acuity over time was assessed using a mixed-effects model. MAIN OUTCOME MEASURES: Best-corrected visual acuity. RESULTS: After excluding eyes that underwent cataract surgery simultaneously with implant surgery, among the 479 eyes in the MUST Trial, 117 eyes (28 eyes in the systemic, 89 in the implant group) in 82 patients underwent cataract surgery during the first 2 years of follow-up. Overall, visual acuity increased by 23 letters from the preoperative visit to the 3-month visit (95% confidence interval [CI], 17-29 letters; P < 0.001) and was stable through 9 months of follow-up. Eyes presumed to have a more severe cataract, as measured by inability to grade vitreous haze, gained an additional 42 letters (95% CI, 34-56 letters; P < 0.001) beyond the 13-letter gain in eyes that had gradable vitreous haze before surgery (95% CI, 9-18 letters; P < 0.001) 3 months after surgery, making up for an initial difference of -45 letters at the preoperative visit (95% CI, -56 to -34 letters; P < 0.001). Black race, longer time from uveitis onset, and hypotony were associated with worse preoperative visual acuity (P < 0.05), but did not affect postsurgical recovery (P > 0.05, test of interaction). After adjusting for other risk factors, there was no significant difference in the improvement in visual acuity between the 2 treatment groups (implant vs. systemic therapy, 2 letters; 95% CI, -10 to 15 letters; P = 0.70). CONCLUSIONS: Cataract surgery resulted in substantial, sustained, and similar visual acuity improvement in the eyes of patients with uveitis treated with the fluocinolone acetonide implant or standard systemic therapy.

ENDOPHTHALMITIS AFTER INTRAVITREAL INJECTION: Role of Prophylactic Topical Ophthalmic Antibiotics.

PURPOSE: To determine the rate of postintravitreal injection endophthalmitis and to assess microbiological features and outcomes with and without the use of peri-intravitreal injection topical ophthalmic antibiotics. METHODS: Consecutive series of endophthalmitis cases retrospectively identified after intravitreal injection at a multicenter, retina-only referral practice (Retina Consultants of Houston) from January 1, 2011 to December 31, 2014. Prophylactic peri-intravitreal injection topical antibiotics were routinely used during the initial 12-month period (January 1, 2011-December 31, 2011) and not used in the final 24-month period (January 1, 2013-December 31, 2014). Main outcome measures were incidence of endophthalmitis, microbiology results, treatment strategies, and visual outcomes. RESULTS: Of 90,339 intravitreal injections, 30 cases of endophthalmitis were identified (endophthalmitis rate = 0.033%; 95% confidence interval, 0.021-0.045%; or approximately 1 of 3,011 intravitreal injections). The most common organisms isolated were coagulase-negative staphylococci (n = 10, 33%), followed by Streptococcus mitis (n = 2, 7%). Fourteen cases (47%) were culture negative. Peri-intravitreal injection topical antibiotic prophylaxis did not decrease the rate of endophthalmitis (0.035% [95% CI, 0.007-0.064%] with antibiotic use versus 0.021% [95% CI, 0.008-0.033%] without antibiotic use; P = 0.261). CONCLUSION: The risk of endophthalmitis after intravitreal injection remains low, with coagulase-negative staphylococci and Streptococcus mitis the most common bacterial isolates identified. Prophylactic peri-intravitreal injection topical ophthalmic antibiotic use did not decrease the endophthalmitis rate.

TLR2/6 and TLR4-activated macrophages contribute to islet inflammation and impair beta cell insulin gene expression via IL-1 and IL-6.

AIMS/HYPOTHESIS: Inflammation contributes to pancreatic beta cell dysfunction in type 2 diabetes. Toll-like receptor (TLR)-2 and -4 ligands are increased systemically in recently diagnosed type 2 diabetes patients, and TLR2- and TLR4-deficient mice are protected from the metabolic consequences of a high-fat diet. Here we investigated the role of macrophages in TLR2/6- and TLR4-mediated effects on islet inflammation and beta cell function. METHODS: Genetic and pharmacological approaches were used to determine the effects of TLR2/6 and TLR4 ligands on mouse islets, human islets and purified rat beta cells. Islet macrophages were depleted and sorted by flow cytometry and the effects of TLR2/6- and TLR4-activated bone-marrow-derived macrophages (BMDMs) on beta cell function were assessed. RESULTS: Macrophages contributed to TLR2/6- and TLR4-induced islet Il1a/IL1A and Il1b/IL1B mRNA expression in mouse and human islets and IL-1ß secretion from human islets. TLR2/6 and TLR4 ligands also reduced insulin gene expression; however, this occurred in a non-beta cell autonomous manner. TLR2/6- and TLR4-activated BMDMs reduced beta cell insulin secretion partly via reducing Ins1, Ins2, and Pdx1 mRNA expression. Antagonism of the IL-1 receptor and neutralisation of IL-6 completely reversed the effects of activated macrophages on beta cell gene expression. CONCLUSIONS/INTERPRETATION: We conclude that islet macrophages are major contributors to islet IL-1ß secretion in response to TLR2/6 and TLR4 ligands. BMDMs stimulated with TLR2/6 and TLR4 ligands reduce insulin secretion from pancreatic beta cells, partly via IL-1ß- and IL-6-mediated decreased insulin gene expression.

Ultra-high performance concrete alleviates ecotoxicological effects in aquatic organisms.

With the advancement of cementitious material technologies, ultra-high performance concretes incorporating nano- and(or) micro-sized particle materials have been developed; however, their environmental risks are still poorly understood. This study investigates the ecotoxicological effects of ultra-high performance concrete (UC) leachate by comparing with that of the conventional concrete (CC) leachate. For this purpose, a dynamic leaching test and a battery test with algae, water flea, and zebrafish were performed using standardized protocols. The conductivity, concentration of inorganic elements (Al, K, Na, and Fe), and total organic concentration were lower in the UC leachate than in the CC leachate. The EC50 values of the CC and UC leachates were 44.9 % and >100 % in algae, and 8.0 % and 63.1 % in water flea, respectively. All zebrafish exposed to the CC and UC leachates survived. A comprehensive evaluation of the ecotoxicity of the CC and UC leachate based on the toxicity classification system (TCS) showed that their toxicity classification was "highly acute toxicity" and "acute toxicity", respectively. Based on the hazard quotient and principal component analysis, Al and(or) K could be significant factors determining the ecotoxicity of concrete leachate. Furthermore, the ecotoxicity of UC could not be attributed to the use of silica-based materials or multi-wall carbon nanotubes. This study is the first of its kind on the ecotoxicity of UC leachate in aquatic environments, and the results of this study can be used to develop environment-friendly UC.

Anti-hypertrophic and anti-oxidant effect of beta3-adrenergic stimulation in myocytes requires differential neuronal NOS phosphorylation.

RATIONALE: Stimulation of ß3-adrenoreceptors (ß3-AR) blunts contractility and improves chronic left ventricular function in hypertrophied and failing hearts in a neuronal nitric oxide synthase (nNOS) dependent manner. nNOS can be regulated by post-translational modification of stimulatory phosphorylation residue Ser1412 and inhibitory residue Ser847. However, the role of phosphorylation of these residues in cardiomyocytes and ß3-AR protective signaling has yet to be explored. OBJECTIVE: We tested the hypothesis that ß3-AR regulation of myocyte stress requires changes in nNOS activation mediated by differential nNOS phosphorylation. METHODS AND RESULTS: Endothelin (ET-1) or norepinephrine induced hypertrophy in rat neonatal ventricular cardiomyocytes (NRVMs) was accompanied by increased ß3-AR gene expression. Co-administration of the ß3-AR agonist BRL-37433 (BRL) reduced cell size and reactive oxygen species (ROS) generation, while augmenting NOS activity. BRL-dependent augmentation of NOS activity and ROS suppression due to NE were blocked by inhibiting nNOS (L-VNIO). BRL augmented nNOS phosphorylation at Ser1412 and dephosphorylation at Ser847. Cells expressing constitutively dephosphorylated Ser1412A or phosphorylated Ser847D nNOS mutants displayed reduced nNOS activity and a lack of BRL modulation. BRL also failed to depress ROS from NE in cells with nNOS-Ser847D. Inhibiting Akt decreased BRL-induced nNOS-Ser1412 phosphorylation and NOS activation, whereas Gi/o blockade blocked BRL-regulation of both post-translational modifications, preventing enhancement of NOS activity and ROS reduction. BRL resulted in near complete dephosphorylation of Ser847 and a moderate rise in Ser1412 phosphorylation in mouse myocardium exposed to chronic pressure-overload. CONCLUSION: ß3-AR regulates myocardial NOS activity and ROS via activation of nNOS involving reciprocal changes in phosphorylation at two regulatory sites. These data identify a novel and potent anti-oxidant and anti-hypertrophic pathway due to nNOS post-translational modification that is coupled to ß3-AR receptor stimulation.

Expanding Psychiatric Treatment in Primary Care Settings: Improved Care Through the Wisconsin Child Psychiatry Consultation Program.

The national shortage of child psychiatrists has resulted in the necessity of primary care providers (PCPs) managing increased mental health concerns of youth. The Wisconsin Child Psychiatry Consultation Program (WI CPCP) is one of several programs throughout the United States which provide PCPs with education, consultation, and resource support related to pediatric mental health. To evaluate initial impact of the program, data from 190 pediatricians and family practitioners from the Wisconsin Health Information Organization (WHIO) were analyzed. Enrollment in the WI CPCP was associated with a significant increase in rates of mental health diagnoses within primary care visits. In addition, the number of providers who made any mental health diagnosis increased from 56% of PCPs pre-enrollment to over 99% post-enrollment. These data provide additional support for pediatric psychiatry consultation programs within primary care.

A Case of Linear Hypertrophic Lichen Planus in a Pediatric Patient.

Lichen planus (LP) is a chronic inflammatory disease of the skin and mucosa. Of the various types, the hypertrophic type is characterized by thickened, purplish hyperkeratotic plaques and nodules. The course of hypertrophic LP tends to be more chronic than those of other types. A 12-year-old girl presented with a 2-year history of warty papules and plaques in a zosteriform configuration along one flank. Histopathology revealed hyperkeratosis and papillomatosis with wedge-shaped hypergranulosis. A lichenoid lymphocytic infiltrate with vacuolar change in the basal layer was evident. She was prescribed oral doxycycline, a topical corticosteroid, and tacrolimus. After 7 weeks, the skin lesions became significantly flattened and faded. LP is less common but more severe in children than in adults. The unilateral, linear hypertrophic type of LP is uncommon. Herein, we report a rare case of linear hypertrophic LP in a child.

Meralgia Paresthetica Review: Update on Presentation, Pathophysiology, and Treatment.

Purpose of Review: Meralgia paresthetica (MP) is a condition characterized by paresthesias, neuropathic pain, and alterations in sensorium of the anterolateral thigh secondary to impingement of the lateral femoral cutaneous nerve (LFCN). MP is generally diagnosed by clinical history and is often a diagnosis of exclusion. When diagnosis remains a challenge, diagnostic modalities such as ultrasound, MRI, electromyography, and nerve conduction studies have been utilized as an adjunct. This review summarizes the most recent medical literature regarding MP, its pathophysiology, presentation, and current treatment options. Recent Findings: Treatment options for patients with MP range from lifestyle modifications and conservative management to surgical procedures. Initial management is often conservative with symptoms managed with medications. When conservative management fails, the next step is regional blocks followed by surgical management. The conflicting data for treatment options for MP highlight how the evidence available does not point to a single approach that's universally effective for treating all patients with MP. Summary: Despite the apparent success at treating MP with regional blocks and surgical interventions, much remains to be known about the dosing, frequency, and optimal interventions due to the inconclusive results of current studies. Further research including randomized controlled trials are needed to better understand the most optimal treatment options for MP including studies with a larger number of participants.

Literature Review: Pericranial Nerve Blocks for Chronic Migraines.

Purpose of Review: Headaches, especially migraines, are one of the most pervasive neurological disorders affecting up to 15.9% of the population. Current methods of migraine treatment include lifestyle changes, pharmacologic, and minimally invasive techniques such as peripheral nerve stimulation (PNS) and pericranial nerve blocks (PNB). Recent Findings: PNBs are used to treat and prevent migraines and involves injection of local anesthetics with or without corticosteroids. PNBs include the greater occipital, supraorbital, supratrochlear, lesser occipital, auriculotemporal, sphenopalantine ganglion, and cervical root nerve blocks. Of the PNBs, the most extensively studied is the greater occipital nerve block (GONB) which has been shown to be an efficacious treatment for migraines, trigeminal neuralgia, hemi-crania continua, and post-lumbar puncture, post-concussive, cluster, and cervicogenic headaches but not medication overuse and chronic tension type headaches. Summary: In this review, we aim to summarize the recent literature on PNBs and their efficacy in the treatment of migraines including a brief discussion of peripheral nerve stimulation.

Review: Discogenic Back Pain: Update on Treatment.

Purpose of Review: Lower back pain (LBP) has a lifetime prevalence of 80% in the United States population. Discogenic back pain (DBP), a subcategory of LBP, occurs as a result of the interverbal disc degeneration without disc herniation. Diagnosis relies on history, physical exam, and imaging such as MRI, provocative discography, or CT discography. Recent Findings: Treatment of DBP involves a multifaceted approach with an emphasis on conservative measures including behavioral modification, pharmacologic management, and other non-pharmacologic interventions with invasive therapy reserved for select patients. Due to the paucity of data on the treatment of DBP, treatment also relies on data derived from treatment of chronic LBP (CLBP). Summary: Despite the scarcity of data for the treatment of DBP, treatments do exist with varying efficacy for DBP. Novel techniques such as the use of biologics may provide another avenue for treatment though further studies are needed to better evaluate the most efficacious regimen for both novel and existing treatments.

Ecotoxicological evaluation of tributyltin toxicity to the equilateral venus clam, Gomphina veneriformis (Bivalvia: Veneridae).

Tributyltin (TBT) is the most common pesticide in marine and freshwater environments. To evaluate the potential ecological risk posed by TBT, we measured biological responses such as growth rate, gonad index, sex ratio, the percentage of intersex gonads, filtration rate, and gill abnormalities in the equilateral venus clam (Gomphina veneriformis). Additionally, the biochemical and molecular responses were evaluated in G. veneriformis exposed to various concentrations of TBT. The growth of G. veneriformis was significantly delayed in a dose-dependent manner after exposure to all tested TBT concentrations. After TBT was administered to G. veneriformis, the gonad index decreased and the sex balance was altered. The percentage of intersex gonads also increased significantly in treated females, whereas no intersex gonads were detected in the solvent control group. Additionally, intersex gonads were detected in male G. veneriformis specimens exposed to relatively high TBT concentrations (20 µg L⁻¹). The filtration rate was also reduced in a dose-dependent manner in TBT-exposed G. veneriformis. We also noted abnormal gill morphology in TBT-exposed G. veneriformis. Furthermore, increases in antioxidant enzyme activities were observed in TBT-exposed G. veneriformis clams, regardless of dosage. Vitellogenin gene expression also increased significantly in a dose-dependent manner in G. veneriformis exposed to TBT. These results provide valuable information regarding our understanding of the toxicology of TBT in G. veneriformis. Moreover, the responses of biological and molecular factors could be utilized as information for risk assessments and marine monitoring of TBT toxicity.

A Case of Vesicular Mycosis Fungoides.

A 44-year-old male presented with 7 months history of nonpruritic round oozing plaques on the extremities and red papules on the trunk. The lesions were resistant to topical and oral steroid prescribed at the other local clinics. Histopathological examination showed parakeratosis with acanthosis and rete ridge elongation as well as spongiotic intraepidermal blisters and dense dermal infiltration of small to medium sized atypical lymphoid cells. Immunohistochemical analysis revealed the lymphocyte infiltrate to be predominantly CD4+ T cells, with CD4/CD8 ratio to be greater than 10:1. Infiltration of large cells that were CD30+ were also noted. This histopathologic findings are consistent with vesicular mycosis fungoides (MF). He was prescribed with narrow-band ultraviolet B twice per week and topical steroid, combined with interferon-α injection for 5 weeks, and his skin lesions significantly faded and were flattened. Vesicular MF is associated with poor prognosis, but our patient was able to show benign course of disease thanks to timely diagnosis. One must consider vesicular MF as a differential for recalcitrant eczematous lesions.

A case of porokeratotic adnexal ostial nevus misdiagnosed as wart.

Porokeratotic adnexal ostial nevus may be misdiagnosed as wart based on clinical appearance and morphology. An accurate diagnosis through skin biopsy is crucial, as is the inclusion of rare disorders such as porokeratotic adnexal ostial nevus in the differential diagnosis.