Loose Skin Research Articles

Mycosis fongoïde chalazodermique associé à un séminome testiculaire métastatique

Granulomatous slack skin (GSS) is an extremely rare subtype of T-cell lymphoma, a variant of mycosis fungoides (MF). Herein, we describe the first reported case of GSS associated with metastatic testicular seminoma. A 28-year-old male patient presented with circumscribed erythematous loose skin masses, especially in the body folds and which had been relapsing for 4years. Skin biopsy showed a loss of elastic fibers and an atypical granulomatous T-cell infiltrate with epidermotropism, enabling a diagnosis of GSS to be made. A biopsy of a retroperitoneal lymphadenopathy showed testicular seminoma metastasis. Patients suffering from GSS have a statistically higher risk of developing a second primary cancer, especially Hodgkin's lymphoma. The association found between GSS and a lymphoproliferative malignancy requires long-term follow-up and determines the patient's prognosis. It is not possible to prove a formal link between GSS and testicular seminoma. However, this case illustrates the value of screening for a second cancer, particularly where extra-cutaneous lesions appear during GSS treatment. Lymph node biopsy should be performed routinely in the event of GSS with possible lymph node involvement.

Severe Phenotype of De Barsy Syndrome in Two Siblings with Novel Mutations in the ALDH18A1 Gene

De Barsy syndrome is a rare autosomal recessive genetic disorder characterized by growth retardation, intellectual disability, a prematurely-aged appearance (progeroid features) and loose skin (cutis laxa) as well as eye abnormalities and others. Some cases of de Barsy syndrome have been linked with mutations PYCR1 or ALDH18A1. We describe a family with two siblings with clinically severe de Barsy syndrome in whom two novel mutations in ALDH18A1 (p.Glu100* and p.Arg724His) were found by clinical exome sequencing using TruSight One panel. The p.Glu100* is a novel mutation predicted to cause absence of the protein. The p.Arg724His has been found with low frequency (0.000016) but not in association with human disease; it has been scored as pathogenic by CADD, MetaSVM, Polyphen2, MutationAssessor, SIFT and MutationTaster. The level of ammonia in serum was determined in second sibling and was in normal range. Amino acid profile in serum revealed decreased concentration of arginine, cytruline, homocysteine, PHE and ornithine. The patients suffer from severe symptoms of GERD such as vomiting, feeding problems instead of multistage therapy including Nissen fundoplication procedure as well as from epilepsy requires complex multidrug therapy. L-Arginine (200 mg/kg) and citrulline (100 mg/kg) were supplemented in the second sibling. The disease leads to premature apoptosis, so antioxidants (coenzyme Q, vitamin A and E) as well as carnitine were supplemented but without spectacular clinical results. We provide clinical description of severe phenotype of de Barsy syndrome. Our molecular report broadens the spectrum of ALDH18A1 mutations causing de Barsy syndrome.

中医阴阳循行的量子元素

量子生物学以微观的波粒二重性突破古典力学对于粒子受制于热力学定律的局限，赋予人类遗传物质得以稳定实现演化的规则性和可预测性。在此之前，去相干的古典物理特性明显遮蔽了我们对量子行为的观察，乃至于面对病理表症的解决之道因为缺少分子尺度的微观考虑，从而限制许许多多医学上重大的发现。巨大个体的生长发育过程会遭遇热力学干扰，最终呈现的是我们所熟悉的古典力学样貌，这现象在物理学上称为去相干，在人类则称为老化。换句话说，当生命体呈现古典定律的粒子性僵硬轨迹，而原本具有波顺应性的量子特性被过滤掉了，这是生命先在性的老化宿命。显现出肌肉皮肤萎缩、弹性下降、皱纹产生、粒线体功能失衡、自由基氧化压力、慢性发炎反应等表症。中医《内经》：「营卫阴阳，如环无端。」依照这个规律而有顺序的循行振动，实现生趣盎然的生命现象。此一生生不息的波、粒二重性，在于法阴阳，和术数，饮食有节，起居有常，不妄作劳，故形与神俱，而终其天年，度百岁乃去。这个源自黄帝内经的组件当可以为人类逆转老化的议题提供值得思考的可能性。 Quantum microscopic biological systems with duality are concerned with the influence of non-trivial quantum phenomena, as opposed to the so-called trivial quantum mechanics present in all biology by reduction to fundamental physics and the law of thermodynamics. These characteristics give the human genetic DNA stable evolution and are able to predictive property. Because the lack of molecular microscopic scale and classical physics of gravity theory interfere with objects wave-like behavior, it limits many of the medical intervention and achievement about human diseases. Quantum phenomena present in the processes of individual biological development system will interfere with an entanglement of physics of gravity theory and thermodynamics. This phenomenon is called de- coherent in physics, and it is also illustrated as ageing in human beings. In other words, when the living environment full with the rigid track of the particles characterization could be considered as a class of quantum phenomena in biological systems are excluded, which may illustrate as the fate of life on aging. Manifestations include muscle and skin atrophy, loose skin elasticity, wrinkling production, mitochondria dysfunction, free radical oxidative stress, chronic inflammation and body function imbalance. This can lead to accelerating ageing. And, of course, it is eventually as scene of death. The yellow Emperor’s classic of Chinese medicine said that yin and yang are interdependent and transform as a circle that is always round endless. Following the yin and yang rhythm, integrated technol-ogy and culture, we will have a regular diet, and not be tired and exhausted in a routine living style. In addition, people should remain calm and avoid excessive desires and fantasies, maintaining the natural purity and clarity of the mind, thus illness and disease can be avoided. The concept supporting the yin-yang-pair model is potentially based on fundamental quantum effects. In ancient times, yin- yang theory advised people to guard themselves against disease-causing factors, and the role of yin-yang recurrence can be subtle as quantum microscale mechanisms. We may consider a biological system that exploits coherent superposition of states of yin-yang recurrence for some practical purposes and provide the possibility for mankind reversing ageing issues, making people happy and have healthy life.

The First Case of Cutis Laxa Type II (Debre Type) Associated with Atrial Septal Defect

Cutis laxa type II (MIM 219200) is a rare congenital disorder, first described by Debre et al. in 1937. During the period from 1937 to 2008, there have been 34 (25 females and 9 males) well-documented published cases of this rare disorder. In 2009, I reported the thirty fifth case of this disorder and I also reviewed the previously published and thirty four well documented cases. A dysmorphic girl was referred at the age of Four years (early April 2016) because of skin abnormality and delayed speech. The girl had cutis laxa with redundant loose skin present from birth. This skin abnormality was evident on the limbs and abdomen. Dysmorphic facial feature included, broad and depressed nasal bridge, and the eyes were wide set with downslanting palpebral fissures. Examination of the cardiovascular system was normal except for the presence of a systolic murmur. Echocardiography revealed the presence of a small atrial septal defect. In this paper, I am reporting the 36th case of Cutis laxa (Debre type) which is the first case to be associated with atrial septal defect.

Population frequency and age of mutation G5741→A in gene NBAS which is a cause of SOPH syndrome in Sakha (Yakutia) Republic

SOPH syndrome (Short stature with Optic nerve atrophy and Pelger–Huët anomaly syndrome, OMIM#614800) is an autosomal recessive hereditary disease characterized by the following main clinical symptoms: postnatal hypoplasia, proportionately short stature, facial dysmorphism, micromelia of feet and hands, limp and loose skin, optic nerve atrophy, and Pelger–Huët anomaly of neutrophils. For the first time, this disease was described in Yakuts. The molecular-genetic study showed that its cause in Yakuts is mutation G5741→A in gene NBAS. On the basis of disequilibrium analysis for linkage of ten microsatellite markers flanking the NBAS gene with the disease, the haplotype of the founder chromosome was determined. The age of the mutation in Yakutia was estimated to be about 804 ± 140 years. The frequency of heterozygous carriers of mutation G5741→A (R1914H) in gene NBAS was found, which averaged 13 per 1000 healthy Yakuts.

Material Properties of Hagfish Skin, with Insights into Knotting Behaviors.

Hagfishes (Myxinidae) often integrate whole-body knotting movements with jawless biting motions when reducing large marine carcasses to ingestible items. Adaptations for these behaviors include complex arrangements of axial muscles and flexible, elongate bodies without vertebrae. Between the axial muscles and the hagfish skin is a large, blood-filled subcutaneous sinus devoid of the intricate, myoseptal tendon networks characteristic of the taut skins of other fishes. We propose that the loose-fitting skin of the hagfish facilitates the formation and manipulation of body knots, even if it is of little functional significance to steady swimming. Hagfish skin is a relatively thick, anisotropic, multilayered composite material comprising a superficial, thin, and slimy epidermis, a middle dermal layer densely packed with fibrous tissues, and a deep subdermal layer comprised of adipose tissue. Hagfish skin is stiffer when pulled longitudinally than circumferentially. Stress-strain data from uniaxial tensile tests show that hagfish skins are comparable in tensile strength and stiffness to the taut skins of elongate fishes that do not engage in knotting behaviors (e.g., sea lamprey and penpoint gunnel). Sheath-core-constructed ropes, which serve as more accurate models for hagfish bodies, demonstrate that loose skin (extra sheathing) enhances flexibility of the body (rope). Along with a loose-fitting skin, the morphologies of hagfish skin parallel those of moray eels, which are also known for generating and manipulating figure-eight-style body knots when struggling with prey.

Pseudoxanthome élastique variant avec déficit en facteurs de coagulation vitamine K-dépendants et perte d’élasticité cutanée

Pseudoxanthoma elasticum (PXE)-like syndrome is characterized by the association of PXE and cutis laxa (CL) features with a deficiency of vitamin K-dependent clotting factors. It was first described in 1971 and was identified as a distinct genetic entity in 2007 with analysis of the GGCX (γ-glutamyl carboxylase) gene, which is involved in congenital deficiency in vitamin K-dependent clotting factors. Here we report a new case of this extremely rare syndrome. A 23-year-old female patient was seen for the emergence of loose and redundant skin following extensive weight loss. She also presented a deficiency of vitamin K-dependent clotting factors. Physical examination revealed excessive, leathery skin folds in the axillary and neck regions. A skin biopsy revealed polymorphous and fragmented elastic fibers in the reticular dermis. These were mineralized, as was demonstrated by Von Kossa staining. The clinical features of CL associated with the histopathological features of PXE and vitamin K-dependent clotting factor deficiency led us to a diagnosis of PXE-like syndrome. A molecular study of the GGCX gene showed compound heterozygosity. The GGCX gene is usually responsible for PXE-like syndrome. GGCX encodes a γ-glutamyl carboxylase necessary for activation of gla-proteins. Gla-proteins are involved both in coagulation factors in the liver and in the prevention of ectopic mineralization of soft tissues. Uncarboxylated forms of gla-proteins in fibroblast would thus enable mineralization and fragmentation of elastic fibers.

Z – Plasty for Medial Cicatricial Ectropion our Experience

Cicatricial ectropion of lower lid is a challenge to most ophthalmologists, as management requires complex procedures like skin grafts. However, Z plasty is a good alternative. Medial cicatricial ectropion is an even more complex problem to deal with, since not much tissue is available to work with, as opposed to lateral ectropion, where loose skin and soft tissue are available. We successfully managed two such cases with Z plasties using a technique which is quite simple and can be easily practiced by general ophthalmologist.

Mixed Epigastric Axial Pattern Flap Following Cutaneous Hemangiosarcoma Excision in a Male Dog

Background: Axial pattern flaps use direct cutaneous arteries to enable closure of a skin defect using a large skin segment. Caudal epigastric axial pattern flaps are highly versatile owing to their wide arc of rotation, which includes the preputial area. The presence of abundant loose and elastic skin allows wider flaps. Hemangiosarcoma (HSA) is a malignant neoplasm of endothelial cells with aggressive local behavior and high metastatic rate; the lungs are the most common site of metastasis. This case report aims to describe the use of a caudal epigastric artery-based flap, with preservation of some cranial epigastric artery branches for penis sparing, following resection of a hemangiosarcoma in the right inguinal region of a male dog.Case: An eight-year-old male Pitt Bull dog was referred with a 15 cm, ulcerated hemangiosarcoma in the right inguinal region, near the prepuce. A similar tumor had been removed from the same location two years before. Previous treatment with oral prednisone did not provide satisfactory results. The patient was suffering from intense chronic blood loss andbacterial infection of the tumor tissue. Thoracic radiographs revealed multiple metastatic nodules. Only mild regenerative anemia was found in blood tests. Considerable reductions in tumor size and in the ulcerated surface, decrease in bleeding, and recovery of appetite were observed after 7 days of administration of piroxicam and cephalexin. Surgical resectionof the tumor was performed as a palliative treatment with a minimal safety margin of 2 cm, which spared the penis. An epigastric skin flap incorporating the second mammary gland was performed preserving branches of cranial epigastric arteries, and was rotated 160° to cover the defect created in the right inguinal region and on the body of the penis. A small suture dehiscence, necrosis of the distal border of the flap, seroma, and multidrug-resistant Escherichia coli infection were observed in the postoperative period. Administration of penicillin V and topical collagenase, placement of a passive drain, and a second surgical procedure to correct the dehiscence were necessary to solve postoperative complications. Piroxicam based metronomic chemotherapy was maintained continuously, as the patient would exhibit worsening of overall condition upon discontinuation of medication. One hundred days after the initial presentation, the animal was euthanized owing to the presence of an osteolytic lesion on the vertebral bodies of L3-L4 and L5-L6, which were suggestive of discosponlylitis or axial bone metastasis.Discussion: Since lung metastases were present, penectomy and uretrostomy were not considered an option, and a pallia tive surgical treatment was performed. In this case report, cranial and caudal epigastric flap presented few complications. Caudal epigastric blood vessels are robust and abundant. Distal necrosis was considered a minor complication and was in accordance with others reports. The multidrug resistant infection was considered a nosocomial infection that arised from a long hospital stay. By inhibiting cyclooxygenase, piroxicam decreases angiogenesis, increases apoptosis, and prolongs disease-free intervals with mild toxicity. An excellent response to preoperative administration of piroxicam was crucial when choosing the postoperative protocol. A signifcant tumor size reduction and a decrease in chronic bleeding associated to improvement in general health were observed with the piroxicam-based treatment. To our knowledge, this is the frst report of a mixed (cranial and caudal) epigastric artery skin flap. This type of flap was considered a good option for correction of large defects in the inguinal region and for preservation of the prepuce and penis.Keywords: hemangiosarcoma, cranial, caudal, penis, sparing.

Generalized acquired cutis laxa type 1: a case report and brief review of literature

Cutis laxa, clinically characterized by loose and pendulous skin related to loss of elastic tissue, is a rare heterogeneous condition. It is classified into congenital and acquired types. We report a case of generalized acquired cutis laxa type 1 in a young man following pruritic urticarial plaques. We have done a brief review of literature.

A study on effect of phototherapy on platelet count in neonates with neonatal hyperbilirubinemia in a tertiary care rural hospital

Background: Phototherapy is one of the most common and invasive methods in treatment of unconjugated hyperbilirubinemia of the neonate. Adverse effects of phototherapy include loose stools, skin rash and dehydration. There are very few studies which show the effect of phototherapy on platelet count. So, this study was done to show the effect of phototherapy on platelet count. Methods: This is a prospective hospital based comparative study on 100 eligible neonates admitted in the Neonatal Intensive Care Unit receiving phototherapy at Adichunchanagiri Institute of Medical Sciences and research hospital, a rural tertiary care hospital, B. G. Nagara, Nagamangala Taluk, Karnataka from December 1st 2013- November 30th 2014. Two samples were taken before and after phototherapy, were taken and analysis was done. The results were analysed statistically. Results: A total of 100 neonates were included in our study of which 55(55%) were males and 45(45%) were females. The mean (+/-SD) platelet counts were 2.23+/-0.28 lak before phototherapy and 1.82+/-0.01 lak after phototherapy. There was a decline in the mean platelet count after phototherapy but it was not statistically significant (p=0.150). However there was a significant decline in mean platelet count in LBW babies. Conclusions: In our study there was a decline in mean platelet count after phototherapy but it was not statistically significant except for LBW babies. The treating Doctor should keep other causes of thrombocytopenia when the patient is receiving phototherapy.

Enhanced membrane antifouling and separation performance by manipulating phase separation and surface segregation behaviors through incorporating versatile modifier

In this study, the copolymers (PSn-co-PEGMAm) with crosslinked structure were synthesized and blended into polythersulfone (PES) matrix to fabricate membranes via surface segregation method. The incorporation of copolymers affected both the phase separation and surface segregation behaviors during membrane fabrication process. On one hand, the copolymers could affect the formation of nodular structure of the as-prepared membranes for increasing the size of polymeric spheres and generating a loose skin layer, which was testified by atomic force microscope (AFM) surface measurement. As a result, the water permeation flux of membranes increased from 166.9Lm−2h−1 for the PES control membrane to 333.0Lm−2h−1 for the PES/PS3-co-PEGMA2 membrane (with 0.80wt% of copolymer content). On the other hand, the hydrophilic PEO segments in the copolymers could spontaneously migrate to and enrich on the membrane surface, which were demonstrated by X-ray photoelectron spectroscopy (XPS) analysis, as a result, the antifouling properties of the membranes were considerably improved. The separation performance of the membranes was evaluated by bovine serum albumin (BSA) aqueous solution as model system. With incorporation of copolymer as versatile modifier, the permeation flux of BSA aqueous solution increased and the rejection efficiency of all the membranes was 100%.

Fibulin-4 E57K Knock-in Mice Recapitulate Cutaneous, Vascular and Skeletal Defects of Recessive Cutis Laxa 1B with both Elastic Fiber and Collagen Fibril Abnormalities

Fibulin-4 is an extracellular matrix protein essential for elastic fiber formation. Frameshift and missense mutations in the fibulin-4 gene (EFEMP2/FBLN4) cause autosomal recessive cutis laxa (ARCL) 1B, characterized by loose skin, aortic aneurysm, arterial tortuosity, lung emphysema, and skeletal abnormalities. Homozygous missense mutations in FBLN4 are a prevalent cause of ARCL 1B. Here we generated a knock-in mouse strain bearing a recurrent fibulin-4 E57K homozygous missense mutation. The mutant mice survived into adulthood and displayed abnormalities in multiple organ systems, including loose skin, bent forelimb, aortic aneurysm, tortuous artery, and pulmonary emphysema. Biochemical studies of dermal fibroblasts showed that fibulin-4 E57K mutant protein was produced but was prone to dimer formation and inefficiently secreted, thereby triggering an endoplasmic reticulum stress response. Immunohistochemistry detected a low level of fibulin-4 E57K protein in the knock-in skin along with altered expression of selected elastic fiber components. Processing of a precursor to mature lysyl oxidase, an enzyme involved in cross-linking of elastin and collagen, was compromised. The knock-in skin had a reduced level of desmosine, an elastin-specific cross-link compound, and ultrastructurally abnormal elastic fibers. Surprisingly, structurally aberrant collagen fibrils and altered organization into fibers were characteristics of the knock-in dermis and forelimb tendons. Type I collagen extracted from the knock-in skin had decreased amounts of covalent intermolecular cross-links, which could contribute to the collagen fibril abnormalities. Our studies provide the first evidence that fibulin-4 plays a role in regulating collagen fibril assembly and offer a preclinical platform for developing treatments for ARCL 1B.

Breast Reshaping Following Bariatric Surgery.

Obesity is a worldwide problem that affects millions of people from a medical and psychological point of view. To solve the related complications, patients should lose weight with the consequent need to be subjected to body contouring due to the presence of a loose and redundant skin. We report our experience in the treatment of the post-bariatric breast. We considered all the post-bariatric patients subjected to a breast reshaping, and we viewed the features of the breast, the type of surgery performed, the outcomes, and the complications. All patients filled out BREAST-Q surveys both preoperatively and after 6 months to study the rate of satisfaction. Ninety post-bariatric patients underwent breast reshaping in the last 5 years. The average age was 40 years old. The follow-up period ranged from 6 months to 5 years. The most represented ptosis was second grade; the favorite technique has been mastopexy with parenchymal remodelling and augmentation with autologous tissue. The mean duration of the surgery has been 3 h. The most represented complications have been delayed healing, unfavorable scarring, hematoma, and seroma. Statistically significant improvements were observed in satisfaction with breast appearance, psychological, and physical well-being. Breast reshaping in post-bariatric patients is a big challenge and only a careful analysis of the degree of ptosis of the breast, its volume and shape, and a clear communication with the patients about the real outcomes and complications can make the winning surgeon.

Phenotypic Expansion of Congenital Disorder of Glycosylation Due to SRD5A3 Null Mutation.

We present a boy, admitted at 4 months, with facial dysmorphism, hypertrichosis, loose skin, bilateral inguinal hernia, severe hypotonia, psychomotor disability, seizures with hypsarrhythmia (West syndrome), hepatosplenomegaly, increased serum transaminases, iris coloboma, glaucoma, corneal clouding and bilateral dilated lateral ventricles, and extra-axial post-cerebellar space. Serum transferrin isoelectrofocusing (IEF) showed a type 1 pattern. Whole-exome genotyping showed a previously reported homozygous nonsense mutation c.320G>A; p.Trp107X in SRD5A3. Epilepsy and glaucoma have been reported only once in the 19 described SRD5A3-congenital glycosylation defect patients, and corneal clouding not at all.

GHK Peptide as a Natural Modulator of Multiple Cellular Pathways in Skin Regeneration.

GHK (glycyl-L-histidyl-L-lysine) is present in human plasma, saliva, and urine but declines with age. It is proposed that GHK functions as a complex with copper 2+ which accelerates wound healing and skin repair. GHK stimulates both synthesis and breakdown of collagen and glycosaminoglycans and modulates the activity of both metalloproteinases and their inhibitors. It stimulates collagen, dermatan sulfate, chondroitin sulfate, and the small proteoglycan, decorin. It also restores replicative vitality to fibroblasts after radiation therapy. The molecule attracts immune and endothelial cells to the site of an injury. It accelerates wound-healing of the skin, hair follicles, gastrointestinal tract, boney tissue, and foot pads of dogs. It also induces systemic wound healing in rats, mice, and pigs. In cosmetic products, it has been found to tighten loose skin and improve elasticity, skin density, and firmness, reduce fine lines and wrinkles, reduce photodamage, and hyperpigmentation, and increase keratinocyte proliferation. GHK has been proposed as a therapeutic agent for skin inflammation, chronic obstructive pulmonary disease, and metastatic colon cancer. It is capable of up- and downregulating at least 4,000 human genes, essentially resetting DNA to a healthier state. The present review revisits GHK's role in skin regeneration in the light of recent discoveries.

Bite injuries of grey seals (Halichoerus grypus) on harbour porpoises (Phocoena phocoena).

Bite-like skin lesions on harbour porpoises (Phocoena phocoena) have been suspected to be caused by grey seals (Halichoerus grypus), and a few field observations have been reported. Bite-like skin lesions observed on stranded animals were characterized by two main components: large flaps of loose or missing skin and blubber with frayed edges and puncture lesions. Definitive demonstration of predation by a grey seal was not reported so far in those stranded animals. In this study, five stranded porpoises with bite-like skin lesions were swabbed for genetic investigations. In addition, the head of a recently dead grey seal was used to mimic bite-like skin injuries on a porpoise carcass. Subsequently, the artificial skin injuries were swabbed, along with the gum of the seal used for inflicting them (positive controls). Total DNA was extracted from the swabs and was used to retrieve a fragment of mitochondrial DNA by PCR. Primers were designed to amplify a specific stretch of mitochondrial DNA known to differ between grey seals and porpoises. The amplicon targeted was successfully amplified from the positive control and from two of the stranded porpoises, and grey seal-specific mitochondrial DNA was retrieved from all those samples. We conclude that (1) it is possible to detect grey seal DNA from dead porpoises even after several days in seawater and (2) bite-like skin lesions found on dead porpoises definitively result from grey seals attacks. The attacks are most likely linked with predation although, in a number of cases, scavenging and aggressive behaviour cannot be excluded.

Retinitis Pigmentosa, Cutis Laxa, and Pseudoxanthoma Elasticum–Like Skin Manifestations Associated with GGCX Mutations

Gamma-glutamyl carboxylase (GGCX) mutations have been reported in patients with a pseudoxanthoma elasticum (PXE)-like phenotype, loose redundant skin, and multiple vitamin K-dependent coagulation factor deficiencies. We report on the clinical findings and molecular results in 13 affected members of two families who had a uniform phenotype consisting of (PXE)-like skin manifestations in the neck and trunk, loose sagging skin of the trunk and upper limbs, and retinitis pigmentosa confirmed by electroretinographies in 10 affected individuals. There were no coagulation abnormalities. Molecular investigations of the ATP-binding cassette subfamily C member 6 did not yield causative mutations. All 13 affected family members were found to be homozygous for the splice-site mutation c.373+3G>T in the GGCX gene. All tested parents were heterozygous for the mutation, and healthy siblings were either heterozygous or had the wild type. We suggest that the present patients represent a hitherto unreported phenotype associated with GGCX mutations. Digenic inheritance has been suggested to explain the variability in phenotype in GGCX mutation carriers. Consequently, the present phenotype may not be explained only by the GGCX mutations only but may be influenced by variants in other genes or epigenetic and environmental factors.

Proton PBS Plan Design and Robustness Evaluation for Head and Neck Cancer

To evaluate the clinical application and robustness of a newly designed proton pencil beam scanning (PBS) planning technique for radiation therapy of patients with bilateral oropharyngeal cancer (OPC). We planned 10 patients with bilateral OPC using two techniques: proton PBS using 2 posterior oblique fields (group 1) and photon volumetric modulated arc therapy (VMAT) using 2 arcs (group 2). During treatment, we obtained weekly surveillance CT scans. To create verification plans, we forward calculated initial plans on verification scans. Post-treatment, we replanned all patients using 3 fields (2 posterior oblique and 1 anterior field, matched at the level of the thyroid notch) (group 3). We performed a dosimetric comparison of the 2 PBS plans (groups 1 and 3) with the VMAT plans (group 2) using an in silico study. To evaluate plan robustness for each group, we compared dosimetric indicators between initial and verification plans for both target volumes and organs at risk (OARs) using Student’s t-test. Target volumes included gross disease + 6 mm margin (CTV1), high risk microscopic disease (CTV2), and low risk microscopic disease (CTV3). We compared the robustness of target coverage in proton PBS plans (groups 1 and 3) with VMAT plans (group 2). All PBS plans resulted in lower integral dose and sparing of the oral cavity, optical apparatus and salivary glands compared to VMAT plans (p<0.05). We performed 39 verification scans; each patient underwent 3 to 6 verification scans. For target volumes, the 2-field proton PBS plan (group 1) did not meet our robustness threshold (p<0.05). For instance, the mean CTV2 D98% for initial plans was 100% compared to 96% for verification plans, with a maximum ΔD98% of -24%. As a result, 2 patients initially planned with 2-field proton PBS (group 1) were moved to treatment with photon VMAT (group 2). On evaluation of target volume dose, loss in CTV coverage in verification plans for group 1 was prominent in the low-neck region where loose skin folds and/or adipose tissues limited reproducibility of patient position. The 3-field proton PBS plan (which does not use beams traversing the posterior low-neck) and the VMAT plan met our robustness threshold (p>0.05) and demonstrated comparable robustness (p>0.05). For OARs, we found no difference in dosimetric indicators between initial and verification scans for all 3 plan groups (p>0.05). PBS has potential dosimetric advantages over IMRT for both 2- and 3-field irradiation geometries. We achieved PBS plan robustness for the entire cohort with 3-field, but not 2-field, irradiation geometry. The proton PBS plans with 3 field irradiation geometry achieved robustness comparable to photon VMAT plans. Future studies will focus on implementing and examining the 3-field proton PBS plans in clinical practice.

Safety and efficacy of ulthera in the rejuvenation of aging lower eyelids: a pivotal clinical trial.

The changes in the periorbital region are among the most prominent features of the aging process in the lower eyelids. Intense focused ultrasound (IFUS), known as the Ulthera System, was designed to correct this process. The current study assessed the safety and efficacy of the Ulthera System. This study enrolled seven adult patients who presented from March 2011 to May 2012 for correction of lower eyelid aging by Ulthera. The subjects were treated using Ulthera 1.5 and 3.0 mm probes. The 1.5 mm probe is used to tighten of loose eyelid skin and the deep dermis, whereas the 3.0 mm probe is used to tighten the orbicularis oculi muscle and the orbital septum. The patients were evaluated for allergic reactions and other side effects. The subjects' satisfaction with clinical photographs and the degree of pain were evaluated. Moreover, orbital computed tomography (CT) and ophthalmologic examinations were performed. The study used CT both as a research tool and as a clinical score system for evaluating aging lower eyelids and performed statistical analysis. Based on the CT images, the difference between the pre- and postoperative distances from the baseline (line between the most inferior point of the supraorbital rim and the most superior point of the infraorbital rim) to the most protruding point of the orbital septum was 0.51 ± 0.23 for the right eye (p < 0.001) and 0.54 ± 0.17 for the left eye (p < 0.001). The subjective score for patient satisfaction was 3.85 ± 0.69. The objective satisfaction scores reported by two blinded researchers were respectively 3.45 ± 1.69 and 3.25 ± 1.43. During the study period, no adverse events and no suspected serious adverse reactions were noted. Tightening of infraorbital laxity and skin can be achieved using the Ulthera System. Patients showed a minimal pain level during treatment, and topical analgesic cream was able to manage pain during the procedure.