Efficacy and safety of tirbanibulin 1% ointment in actinic keratoses: Data from two phase-III trials and the real-life clinical practice presented at the European Academy of Dermatology and Venereology Congress 2022.

BACKGROUND: The 31st European Academy of Dermatology and Venereology (EADV) Congress took place between 7th and 10th of September 2022 in Milan, Italy. OBJECTIVES: We report presented clinical data on the efficacy/effectiveness, safety and tolerability of tirbanibulin 1% ointment that has recently been licensed for actinic keratosis (AK) of the face or scalp in adults. METHODS: Summary of presentations given at the EADV Congress. RESULTS: Prof. Pellacani presented two post hoc analyses from two phase-III trials with AK patients (NCT03285477 [N = 351] and NCT03285490 [N = 351]): A descriptive analysis of medical history, concomitant medications, and safety results confirming a favourable profile for tirbanibulin showing that number of baseline AK lesions was not correlated to severity of local skin reactions. The latter analysis showed that cases of tirbanibulin application site pain or pruritus were few, and most were found to be mild. Prof. Kunstfeld reported six real-life clinical cases in Austria showing good tirbanibulin effectiveness, safety and tolerability for the treatment of new or recurring AK lesions. Results demonstrated that after 2- to 4-month follow-up, tirbanibulin was well tolerated and effective in AK patients. Presentations by Dr. Patel confirmed good outcomes and tolerability of tirbanibulin in Olsen grade 1-2 AK (N = 12) and porokeratosis patients (N = 4) treated once daily for 5 consecutive days in the United Kingdom. Furthermore, real-world experience in solid organ transplant recipients (N = 2) demonstrated effectiveness of tirbanibulin in skin field cancerization treatment. A symposium sponsored by Almirall was conducted during the congress in which Dr. Hadshiew and Dr. Lear brought together their clinical experience in Germany and the United Kingdom respectively. Interesting clinical cases of 5 consecutive days of tirbanibulin treatment compared to other treatments were discussed with attendees, as well as current treatment needs of AK patients. CONCLUSIONS: This article provides an overview of presentations and symposium discussions, summarizing key phase-III results and real-life clinical experience with tirbanibulin shared by dermatologists across Europe.

Huo-Luo-Xiao-Ling (HLXL)-Dan, a Traditional Chinese Medicine, for patients with osteoarthritis of the knee: a multi-site, randomized, double-blind, placebo-controlled phase II clinical trial.

OBJECTIVE: To examine the efficacy and safety of Huo-Luo-Xiao-Ling (HLXL)-Dan, a Traditional Chinese Medicine (TCM), in patients with knee osteoarthritis (OA). DESIGN: A multi-site, randomized, double-blind, placebo-controlled phase II dose-escalation clinical trial was conducted. Eligible patients who fulfilled American College of Rheumatology criteria were randomized to receive either HLXL or placebo. Clinical assessments included measurement of knee pain and function with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), patient global assessment (PGA), and knee pain scores every 2 weeks. A Data and Safety Monitoring Board (DSMB) was established to review the data for ensuring the quality of the trial. RESULTS: In the first stage, 28 participants were randomized to receive either low-dose HLXL-Dan (2400 mg/day) or placebo for 6 weeks. The results showed no statistical difference between the two groups. The study was then re-designed following the recommendation of DSMB. Ninety-two patients were enrolled in the second stage and were randomized to receive either high-dose HLXL-Dan (4000 mg/day for week 1-2, and 5600 mg/day for week 3-8) or placebo for 8 weeks. All outcome assessments showed significant improvements for both groups after 8 weeks but no significant between-group differences. The change (mean ± SD) of WOMAC pain and WOMAC function scores of HLXL and placebo group after 8 weeks were -1.2 ± 1.7 vs -1.4 ± 1.5, and -1.1 ± 1.6 vs -1.3 ± 1.5 respectively. No serious adverse events were reported. CONCLUSION: Although safe to use, an 8-week treatment of HLXL-Dan was not superior to placebo for reduction in pain or functional improvement in patients with knee OA. CLINICAL TRIAL REGISTRATION NUMBER: Clinicaltrials.gov (NCT00755326).

Hard two-body photodisintegration of 3He.

We have measured cross sections for the γ(3)He → pd reaction at photon energies of 0.4-1.4 GeV and a center-of-mass angle of 90°. We observe dimensional scaling above 0.7 GeV at this center-of-mass angle. This is the first observation of dimensional scaling in the photodisintegration of a nucleus heavier than the deuteron.

Anatomical categorization of isolated non-focal dystonia: novel and existing patterns using a data-driven approach.

According to expert consensus, dystonia can be classified as focal, segmental, multifocal, and generalized, based on the affected body distribution. To provide an empirical and data-driven approach to categorizing these distributions, we used a data-driven clustering approach to compare frequency and co-occurrence rates of non-focal dystonia in pre-defined body regions using the Dystonia Coalition (DC) dataset. We analyzed 1,618 participants with isolated non-focal dystonia from the DC database. The analytic approach included construction of frequency tables, variable-wise analysis using hierarchical clustering and independent component analysis (ICA), and case-wise consensus hierarchical clustering to describe associations and clusters for dystonia affecting any combination of eighteen pre-defined body regions. Variable-wise hierarchical clustering demonstrated closest relationships between bilateral upper legs (distance = 0.40), upper and lower face (distance = 0.45), bilateral hands (distance = 0.53), and bilateral feet (distance = 0.53). ICA demonstrated clear grouping for the a) bilateral hands, b) neck, and c) upper and lower face. Case-wise consensus hierarchical clustering at k = 9 identified 3 major clusters. Major clusters consisted primarily of a) cervical dystonia with nearby regions, b) bilateral hand dystonia, and c) cranial dystonia. Our data-driven approach in a large dataset of isolated non-focal dystonia reinforces common segmental patterns in cranial and cervical regions. We observed unexpectedly strong associations between bilateral upper or lower limbs, which suggests that symmetric multifocal patterns may represent a previously underrecognized dystonia subtype.

Electroacupuncture inhibition of hyperalgesia in an inflammatory pain rat model: involvement of distinct spinal serotonin and norepinephrine receptor subtypes.

BACKGROUND: Although acupuncture analgesia is well documented, its mechanisms have not been thoroughly clarified. We previously showed that electroacupuncture (EA) activates supraspinal serotonin- and norepinephrine-containing neurones that project to the spinal cord. This study investigates the involvement of spinal alpha(2)-adrenoceptors (α2-ARs) and 5-hydroxytryptamine (serotonin) receptors (5-HTRs) in EA effects on an inflammatory pain rat model. METHODS: Inflammatory hyperalgesia was induced by injecting complete Freund's adjuvant (CFA, 0.08 ml) into the plantar surface of one hind paw and assessed by paw withdrawal latency (PWL) to a noxious thermal stimulus. The selective α2a-AR antagonist BRL-44408, α2b-AR antagonist imiloxan hydrochloride, 5-HT2B receptor (5-HT2BR) antagonist SB204741, 5-HT3R antagonist LY278584, or 5-HT1AR antagonists NAN-190 hydrobromide, or WAY-100635 were intrathecally administered 20 min before EA or sham EA, which was given 2 h post-CFA at acupoint GB30. RESULTS: EA significantly increased PWL compared with sham [7.20 (0.46) vs 5.20 (0.43) s]. Pretreatment with α2a-AR [5.35 (0.45) s] or 5-HT1AR [5.22 (0.38) s] antagonists blocked EA-produced anti-hyperalgesia; α2b-AR, 5-HT2BR, and 5-HT3R antagonist pretreatment did not. Sham plus these antagonists did not significantly change PWL compared with sham plus vehicle, indicating that the antagonists had little effect on PWL. Immunohistochemical staining demonstrated that α2a-ARs are on primary afferents and 5-HT1ARs are localized in N-methyl-d-aspartic acid (NMDA) subunit NR1-containing neurones in the spinal dorsal horn. CONCLUSIONS: The data show that α2a-ARs and 5-HT1ARs are involved in the EA inhibition of inflammatory pain and that the NMDA receptors are involved in EA action.

Evidence for functional specialization of hippocampal subfields detected by MR subfield volumetry on high resolution images at 4 T.

Animal studies suggest an involvement of CA3 and dentate gyrus (CA3&DG) in memory encoding and early retrieval and an involvement of CA1 in late retrieval, consolidation and recognition. The aim of this study was to test if similar associations could be found between hippocampal subfield volumes measured in vivo using a manual parcellation scheme and selected scores of the California Verbal Learning Test II (CVLTII): total immediate free recall discriminability (IFRD), short free recall discriminability (SFRD), and delayed recall discriminability (DRD). 50 elderly subjects (25 controls and 25 cognitively impaired subjects) had CVLTII and high resolution hippocampal MRI at 4T. Entorhinal cortex, subiculum, CA1, CA1-CA2 transition zone, and CA3&DG were manually marked on five slices in the anterior hippocampal body on the MRI. Pearson correlations followed by stepwise regression analysis were used to test for associations between subfield volumes and CVLTII. IFRD and SFRD, which are measures of encoding/early retrieval, were associated with CA3&DG, and DRD, which measures consolidation/late retrieval, with CA1. These preliminary findings demonstrate that subfield volumetry has the potential to study non invasively subfield specific memory functions.

Precise extraction of the induced polarization in the 4He(e,e'p)3H reaction.

We measured with unprecedented precision the induced polarization P(y) in (4)He(e,e'p)(3)H at Q(2)=0.8 and 1.3 (GeV/c)(2). The induced polarization is indicative of reaction-mechanism effects beyond the impulse approximation. Our results are in agreement with a relativistic distorted-wave impulse approximation calculation but are overestimated by a calculation with strong charge-exchange effects. Our data are used to constrain the strength of the spin-independent charge-exchange term in the latter calculation.

Gamma interferon is the lymphokine and beta interferon the monokine responsible for inhibition of fibroblast collagen production and late but not early fibroblast proliferation.

Human peripheral blood mononuclear cells activated with concanavalin A (Con A) or lipopolysaccharide (LPS) produce, respectively, lymphokines (LK) of 50,000 Mr or monokines (MK) of 20,000 Mr that inhibit the growth and collagen production of cultured human dermal fibroblasts. Because antigenic typing of the antiviral activity of these LK and MK preparations revealed that LK contained mainly gamma interferon (IFN-gamma), and MK, primarily IFN-beta, we investigated if any of the fibroblast-inhibiting activities could be attributed to human IFN. Unlike LK and MK, which act within 24 h to inhibit the growth of subconfluent foreskin and adult dermal fibroblasts, samples of purified, natural derived IFN-alpha, -beta, and -gamma and recombinant DNA-derived IFN-alpha 2 and -gamma were ineffective inhibitors at 24 h and required 48-72 h to significantly inhibit growth. However, all IFN did mimic LK/MK action in causing concentration-dependent inhibition of collagen production by confluent fibroblast microcultures. Furthermore, the collagen production-inhibiting activity of Con A-induced LK supernatant and its 50,000 Mr fraction was completely suppressed by 10(3) neutralizing U/ml of either polyclonal or monoclonal antibody to IFN-gamma, while polyclonal antibodies to IFN-alpha and -beta had no effect. Similarly, the collagen production-inhibiting activity of LPS-induced MK supernatant and its 20,000 Mr fraction was suppressed by polyclonal anti-IFN-beta but not by anti-IFN-alpha or -gamma. Anti-IFN failed to reverse early-acting LK or MK growth-inhibiting activities. These data suggest collagen production-inhibiting LK and MK are IFN-gamma and IFN-beta, respectively, and that early acting, growth-inhibiting LK and MK are not IFN.

Tensor correlations measured in 3He(e,e' pp)n.

We have measured the 3He(e,e' pp)n reaction at an incident energy of 4.7 GeV over a wide kinematic range. We identified spectator correlated pp and pn nucleon pairs by using kinematic cuts and measured their relative and total momentum distributions. This is the first measurement of the ratio of pp to pn pairs as a function of pair total momentum p(tot). For pair relative momenta between 0.3 and 0.5 GeV/c, the ratio is very small at low p(tot) and rises to approximately 0.5 at large p(tot). This shows the dominance of tensor over central correlations at this relative momentum.

Absorption of the ω and ϕ mesons in nuclei.

Because of their long lifetimes, the ω and ϕ mesons are the ideal candidates for the study of possible modifications of the in-medium meson-nucleon interaction through their absorption inside the nucleus. During the E01-112 experiment at the Thomas Jefferson National Accelerator Facility, the mesons were photoproduced from 2H, C, Ti, Fe, and Pb targets. This Letter reports the first measurement of the ratio of nuclear transparencies for the e+e- channel. The ratios indicate larger in-medium widths compared with what have been reported in other reaction channels. The absorption of the ω meson is stronger than that reported by the CBELSA-TAPS experiment and cannot be explained by recent theoretical models.

Polarization transfer in the 4He(e,e'p)3H reaction at Q2=0.8 and 1.3 (GeV/c)2.

Proton recoil polarization was measured in the quasielastic 4He(e,e'p)3H reaction at Q{2}=0.8 and 1.3 (GeV/c){2} with unprecedented precision. The polarization-transfer coefficients are found to differ from those of the 1H(e,e'p) reaction, contradicting a relativistic distorted-wave approximation and favoring either the inclusion of medium-modified proton form factors predicted by the quark-meson coupling model or a spin-dependent charge-exchange final-state interaction. For the first time, the polarization-transfer ratio is studied as a function of the virtuality of the proton.

A BAC-based physical map of the major autosomes of Drosophila melanogaster.

We constructed a bacterial artificial chromosome (BAC)-based physical map of chromosomes 2 and 3 of Drosophila melanogaster, which constitute 81% of the genome. Sequence tagged site (STS) content, restriction fingerprinting, and polytene chromosome in situ hybridization approaches were integrated to produce a map spanning the euchromatin. Three of five remaining gaps are in repeat-rich regions near the centromeres. A tiling path of clones spanning this map and STS maps of chromosomes X and 4 was sequenced to low coverage; the maps and tiling path sequence were used to support and verify the whole-genome sequence assembly, and tiling path BACs were used as templates in sequence finishing.

The genome sequence of Drosophila melanogaster.

The fly Drosophila melanogaster is one of the most intensively studied organisms in biology and serves as a model system for the investigation of many developmental and cellular processes common to higher eukaryotes, including humans. We have determined the nucleotide sequence of nearly all of the approximately 120-megabase euchromatic portion of the Drosophila genome using a whole-genome shotgun sequencing strategy supported by extensive clone-based sequence and a high-quality bacterial artificial chromosome physical map. Efforts are under way to close the remaining gaps; however, the sequence is of sufficient accuracy and contiguity to be declared substantially complete and to support an initial analysis of genome structure and preliminary gene annotation and interpretation. The genome encodes approximately 13,600 genes, somewhat fewer than the smaller Caenorhabditis elegans genome, but with comparable functional diversity.

Do postsurgical interventions optimize ultimate scar cosmesis.

Keloids and other scars are different manifestations of the normal wound healing process. If located in visible areas, scars may have a psychological impact that could affect the quality of life of the scar-bearing population. Good preoperatory planning including hiding incisions in natural anatomical landmarks or placing them parallel to relaxed skin tension lines are among the techniques used to improve the cosmesis of scars. Once a prominent or noticeable scar has developed, multiple therapeutic modalities can be applied including surgical excision, although high recurrence rates precludes its use as monotherapy. Several advanced surgical correction techniques including Z-plasty and W-plasty may be useful in repositioning scars. Other modalities that have been reported to improve scar cosmesis include cryosurgery, radiotherapy, lasers, and skin substitute grafts. Adjuvant postsurgical treatment modalities have reduced dramatically the recurrence rates associated with the removal of the scar. In this review of the literature the authors discuss evidence based data related to the abovementioned modalities and other topical and intralesional therapies including occlusion, compression, silicone, corticosteroids, interferons, imiquimod, resiquimod, tacrolimus, 5-fluorouracil, retinoids, as well as the role of several over-the-counter agents such as onion extract, vitamin E and the combination of hydrocortisone, vitamin E and silicone. Finally, they address newer modalities including vascular endothelial growth factor inhibitor, transforming growth factor-3, interleukin-10, mannose-6-phosphate, UVA-1, narrowband UVB, intense pulsed light and photodynamic therapy. Ultimately, the decision of choosing the most appropriate postexcisional management treatment should be taken by physicians on a case-by-case basis in order to obtain the best cosmetically acceptable results.

Electroacupuncture alleviates chemotherapy-induced pain through inhibiting phosphorylation of spinal CaMKII in rats.

BACKGROUND: Current medical treatments for chemotherapy-induced pain (CIP) are either ineffective or have adverse side effects. Acupuncture may alleviate CIP, but its effectiveness against this condition has not been studied. Paclitaxel causes neuropathic pain in cancer patients. METHODS: We evaluated the effects of electroacupuncture (EA) on paclitaxel-induced CIP in a rat model. Paclitaxel (2 mg/kg) or vehicle was injected (i.p.) on alternate days of 0-6. The resulting pain was treated with 10 Hz/2 mA/0.4 ms pulse EA for 30 min at the equivalent of human acupoint GB30 (Huantiao) once every other day between days 14 and 26. For sham control, EA needles were inserted into GB30 without stimulation. Von Frey filaments with bending forces of 2-8 g and 15 g were used to assess mechanical allodynia and hyperalgesia, respectively, on day 13 and once every other day between 14-26 days and then for 2-3 weeks after EA treatment. RESULTS: Compared to sham control, EA significantly alleviated paclitaxel-induced mechanical allodynia and hyperalgesia, as shown by less frequent withdrawal responses to the filaments. The alleviation of allodynia/hyperalgesia lasted up to 3 weeks after the EA treatment. EA significantly inhibited phosphorylation of Ca2+ /calmodulin-dependent protein kinase II (CaMKII) in the spinal cord. KN-93, a selective inhibitor of p-CaMKII, inhibited mechanical allodynia/hyperalgesia and p-CaMKII. 5-HT1A receptor antagonist blocked EA inhibition of allodynia/hyperalgesia and p-CaMKII. CONCLUSIONS: Electroacupuncture activates 5-HT 1A receptors in the spinal cord and inhibits p-CaMKII to alleviate both allodynia and hyperalgesia. The data support acupuncture/EA as a complementary therapy for CIP. SIGNIFICANCE: Electroacupuncture (EA) activates spinal 5-HT1A receptors to inhibit p-CaMKII to alleviate paclitaxel-induced pain. Acupuncture/EA may be used as a complementary therapy for CIP.

Persistence of a reduced-collagen-producing phenotype in cultured scleroderma fibroblasts after short-term exposure to interferons.

Transient exposure to inflammation-associated, fibroblast-stimulatory factors appears to initiate fibrosis by inducing the persistently activated phenotypes displayed by fibroblast cultures derived from scleroderma skin and other fibrotic tissues. To determine whether one class of fibroblast-inhibitory factors, the interferons (IFNs), plays a role in terminating fibrosis by acting as persistent fibroblast deactivators, we inhibited (40-60%) the growth and collagen production of normal dermal fibroblasts and hypercollagen-producing scleroderma fibroblasts by short-term exposure to IFN-alpha, beta, or gamma. During subsequent subculture in the absence of IFNs, the growth and collagen production of normal fibroblasts and the growth of scleroderma fibroblasts increased to untreated control levels after two to three passages. In contrast, collagen production by scleroderma fibroblasts remained inhibited for at least five passages (18 cell doublings) and was not further suppressed by subsequent IFN exposure. These data suggest that IFNs may help terminate fibrosis by suppressing persistently activated fibroblast functions.

Molecular analysis of the beta-thalassemia phenotype associated with inheritance of hemoglobin E (alpha 2 beta2(26)Glu leads to Lys).

Inheritance of the gene for betaE-globin is associated with hypochromia and microcytosis, reminiscent of typical heterozygous beta-thalassemia. Patients with hemoglobin (Hb)E-beta-thalassemia exhibit clinical phenotypes of severe beta-thalassemia, a circumstance not encountered in other compound heterozygous states for structural beta-chain mutations and beta-thalassemia. We have analyzed the kinetics of globin synthesis and the levels of globin messenger (m) RNA accumulation in patients with Hb E-beta-thalassemia and Hb E trait. The initial rate of beta-globin synthesis (betaE/alpha=0.20-0.34) was less than expected on the basis of gene dosage, or comparable studies of other compound heterozygous states for beta-thalassemia and structurally abnormal beta-chains. betaE-globin synthesis was not only reduced during short-term incubations (1-5 min), but also remained relatively unchanged during long-term pulse or chase incubations up to 5h. Analysis of globin mRNA by cell-free translation and molecular hybridization confirmed that the unexpectedly low levels of betaE-globin synthesis were associated with comparable reduction in the levels of beta-globin mRNA. In Hb E-beta-thalassemia the betaA + betaE (alpha globin nRNA ratio observed were substantially lower than those obtained from reticulocytes of patients with heterozygous beta-thalassemia, or Hb S-betaO-thalassemia, while in Hb E trait, the betaA + betaE/alpha mRNA ratio was in the ranged observed for beta-thalassemia trait. The betaE-globin gene specifies reduced accumulation of betaE-globin mRNA, a property characteristic of other forms of beta-thalassemia. The beta-thalassemia phenotype associated with inheritance of Hb E is thus determined at the level of beta-globin mRNA metabolism.

Herbal medicine for low back pain.

BACKGROUND: Low-back pain is a common condition and a substantial economic burden in industrialized societies. A large proportion of patients with chronic low-back pain use complementary and alternative medicine (CAM), visit CAM practitioners, or both. Several herbal medicines have been purported for use in low-back pain. OBJECTIVES: To determine the effectiveness of herbal medicine for non-specific low-back pain. SEARCH STRATEGY: We searched the following electronic databases: Cochrane Complementary Medicine Field Trials Register (Issue 3, 2005), MEDLINE (1966 to July 2005), EMBASE (1980 to July 2005); checked reference lists in review articles, guidelines and retrieved trials; and personally contacted individuals with expertise in this very specialized area. SELECTION CRITERIA: We included randomized controlled trials, examining adults (over 18 years of age) suffering from acute, sub-acute or chronic non-specific low-back pain. The interventions were herbal medicines, defined as plants that are used for medicinal purposes in any form. Primary outcome measures were pain and function. DATA COLLECTION AND ANALYSIS: Two authors (JJG & MVT) conducted the database searches. One author contacted content experts and acquired relevant citations. Full references and abstracts of the identified studies were downloaded. A hard copy was retrieved for final inclusion decisions. Methodological quality and clinical relevance were assessed separately by two individuals. Disagreements were resolved by consensus. MAIN RESULTS: Ten trials were included in this review. Two high quality trials examining the effects of Harpagophytum Procumbens (Devil's Claw) found strong evidence that daily doses standardized to 50 mg or 100 mg harpagoside were better than placebo for short-term improvements in pain and rescue medication. Another high quality trial demonstrated relative equivalence to 12.5 mg per day of rofecoxib (Vioxx). Two trials examining the effects of Salix Alba (White Willow Bark) found moderate evidence that daily doses standardized to 120 mg or 240 mg salicin were better than placebo for short-term improvements in pain and rescue medication. An additional trial demonstrated relative equivalence to 12.5 mg per day of rofecoxib. Three low quality trials on Capsicum Frutescens (Cayenne), examining various topical preparations, found moderate evidence that Capsicum Frutescens produced more favourable results than placebo and one trial found equivalence to a homeopathic ointment. AUTHORS' CONCLUSIONS: Harpagophytum Procumbens, Salix Alba and Capsicum Frutescens seem to reduce pain more than placebo. Additional trials testing these herbal medicines against standard treatments are needed. The quality of reporting in these trials was generally poor. Trialists should refer to the CONSORT statement extension for reporting trials of herbal medicine interventions.

Acupuncture for treatment of irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS), a disorder of altered bowel habits associated with abdominal pain or discomfort. The pain, discomfort, and impairment from IBS often lead to healthcare medical consultation (Talley 1997) and workplace absenteeism, and associated economic costs (Leong 2003). A recent randomized controlled trial shows variable results but no clear evidence in support of acupuncture as an effective treatment for IBS (Fireman 2001). OBJECTIVES: The objective of this systematic review is to determine whether acupuncture is more effective than no treatment, more effective than 'sham' (placebo) acupuncture, and as effective as other interventions used to treat irritable bowel syndrome. Adverse events associated with acupuncture were also assessed. SEARCH STRATEGY: The following electronic bibliographic databases were searched irrespective of language, date of publication, and publication status: MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library, EMBASE, the Chinese Biomedical Database, the Cumulative Index to Nursing and Allied Health (CINAHL), and the Allied and Complementary Medicine Database (AMED). References in relevant reviews and RCTs were screened by hand. The last date for searching for studies was 7 February 2006. SELECTION CRITERIA: Published reports of randomized controlled trials (RCTs) and quasi-randomised trials of acupuncture therapy for IBS. DATA COLLECTION AND ANALYSIS: All eligible records identified were dually evaluated for eligibility and dually abstracted. Methodological quality was assessed using the Jadad scale and the Linde Internal Validity Scale. Data from individual trials were combined for meta-analysis when the interventions were sufficiently similar. Heterogeneity was assessed using the I squared statistic. MAIN RESULTS: Six trials were included. The proportion of responders, as assessed by either the global symptom score or the patient-determined treatment success rate, did not show a significant difference between the acupuncture and the sham acupuncture group with a pooled relative risk of 1.28 (95% CI 0.83 to 1.98; n=109). Acupuncture treatment was also not significantly more effective than sham acupuncture for overall general well-being, individual symptoms (e.g., abdominal pain, defecation difficulties, diarrhea, and bloating), the number of improved patients assessed by blinded clinician, or the EuroQol score. For two of the studies without a sham control, acupuncture was more effective than control treatment for the improvement of symptoms: acupuncture versus herbal medication with a RR of 1.14(95% CI 1.00 to 1.31; n=132); acupuncture plus psychotherapy versus psychotherapy alone with a RR of 1.20 (95% CI 1.03 to 1.39; n=100). When the effect of ear acupuncture treatment was compared to an unclearly specified combination of one or more of the drugs diazepam, perphenazine or domperidone, the difference was not statistically significant with a RR of 1.49(95% CI 0.94 to 2.34; n=48). AUTHORS' CONCLUSIONS: Most of the trials included in this review were of poor quality and were heterogeneous in terms of interventions, controls, and outcomes measured. With the exception of one outcome in common between two trials, data were not combined. Therefore, it is still inconclusive whether acupuncture is more effective than sham acupuncture or other interventions for treating IBS.

Immunological strategies to fight skin cancer.

Skin cancer is the most common human cancer, and is currently considered a global epidemic. Recently, there has been a growing interest in immunomodulators, or up-regulators of the immune response, for the treatment and cure of various forms of skin cancer, including melanoma and nonmelanoma skin cancers, cutaneous T-cell lymphoma, Kaposi's sarcoma, cutaneous extramammary Paget's disease, and vulvar intraepithelial carcinoma neoplasia. Strategies to augment the host's immune response against cancer cells and/or cancer cell antigenicity have been investigated, including recombinant cytokines, immunomodulators, dendritic cell immunization, tumor antigen vaccination, T-cell-based immunotherapy, and gene therapy. Although the current standard of care for most of these cancers includes Mohs micrographic surgery, curettage, and cryo-, laser-, or radiotherapy, immunomodulators are becoming essential in the treatment of patients who are poor surgical candidates and/or require noninvasive therapy.