Part 1 of this article outlined the extensive osseous adaptations around the hip that occurred in the development of a habitual bipedal gait in modern humans. The shortest summary of these osseous changes is ‘double extension’, i.e. extension of both the hip joint and the lumbar spine. Not surprisingly, these osseous changes went hand in hand with major muscular changes. The primary changes that accompanied the double extension were changes in relative muscle volume for the quadriceps, gluteus maximus and hamstrings, changes in moment arms for the iliopsoas, gluteus maximus and hamstrings, a change in function for the gluteus medius and minimus, while the functional anatomy of the adductors and hip rotators changed only slightly. The effect of these osseous and muscular changes was improved energy efficiency of human bipedal walking and (long distance) running. However, this occurred at the expense of maximum power, characteristic for activities such as tree climbing (in the apes), but equally so for sprinting. Recognizing these changes and their consequences may help us better understand and treat soft-tissue disorders around the hip. No mammal has a habitual extended hip joint position like humans do. Other mammals, including the non-human apes , have a ‘mid-flex’ hip position as their default. In the preceding section of this two-part article, we have summarized the extensive osseous adaptations required for the obligate bipedal human gait. Below, we focus on the accompanying soft-tissue changes, exploring the consequences of the extended stance on the configuration of the muscles and tendons around the hip, particularly the hip extensors, flexors and abductors. Understanding how these muscles have evolved in the human lineage could be helpful to better understand their injury and overuse patterns.Fossil preservation of soft tissues is extremely rare, and evolutionary changes of musculature have to be interpreted from the rugosities where muscles are thought to originate. To infer soft-tissue changes, we have to rely more on comparative anatomy than for skeletal changes. Comparative anatomical studies of extant primates allow us to establish form–function relationships, but we should bear in mind that since the last common ancestor of humans and chimpanzees, ∼7 million years ago, both lineages have evolved (though the last common ancestor was more similar to living apes than to living humans).Ardipithecus ramidus of 4.4 million years old, had a pelvis already much more human- than chimpanzee-like , 3611, 3In running, the long Achilles tendon stores and releases elastic energy during stance phase. The efficiency of this stretch and recoil of the Achilles tendon goes a long way to explain the difference in metabolic efficiency between runners . This isInjuries or overuse of muscle-tendon units around the human hip (other than the hamstrings) are relatively rare, and so are degenerative soft-tissue lesions around the hip. The exception is the gluteus medius which can develop degenerative  tendon tears, either without or with trochanteric pain and gait symptoms. But, other than the hamstring and gluteus medius, most soft-tissue problems around the hip seen in orthopaedic practice may in fact be iatrogenic. Failure to heal of detached tendons, protruding cement or total hip components can cause pain and symptoms related to the lesser gluteals, external rotators and iliopsoas.The human ‘gluteus maximus’ became important to extend the pelvis and spine over the hips, and stabilize it in the sagittal plane. It is particularly important during running . Yet, inIn strong contrast to the gluteus maximus, ‘gluteus medius’ injuries are relatively common and, unfortunately, many of these are iatrogenic. Abductor weakness with pain and gait disorders can result from the direct lateral  approach to the hip. Dehiscence or denervation of the anterior portion of the gluteus medius after this approach is reported in ∼50%  and 10% The gluteus medius performs most of the abduction work in bipedal gait of the three abductors, which further include gluteus minimus and tensor fasciae latae (TFL). The gluteus medius is a thick, relatively short muscle, and this architecture is one of the characteristics that signals its primary function is power rather than speed. Due to the length of their muscle moment arm, which is about half that of the moment arm of the ground reaction force , the abductors have to produce a force of approximately twice body weight during monopedal stance during normal gait . When exA further indication of the high loads on the abductor mechanism at its insertions is that pain around the greater trochanter in the absence of abductor tendon abnormalities is a common entity . This grIn the ‘new’ field of soft-tissue endoscopy around the hip, surgeons now perform trochanteric bursectomies, with or without lengthening of the iliotibial band for GTPS. However, none of the small single-surgeon case series reported uses control groups, and no comparison between open and endoscopic surgery has been made .Again, the most common cause for persistent iliopsoas pain in orthopaedic practice appears iatrogenic rather than overuse or sports , 60. Durde novo after total hip arthroplasty.Iliopsoas impingement with tendonitis/bursitis is characterized by pain with active hip flexion, for example when getting out of a car (‘car sign’ ) or walkWhen, despite conservative therapy of stretching exercises and steroid injection, these symptoms persist for months, tenotomy of the psoas major tendon is an option. This is usually performed at the insertion at the lesser trochanter, at the head–neck junction or at the anterior acetabular rim. Although continuity of the iliopsoas muscle complex is preserved irrespective of the location of psoas tenotomy , MRI stuThe external rotators of the hip are detached with the posterior approach to the hip, and whether their repair remains intact postoperatively is reported variably . But theThe development of human habitual bipedal gait was characterized by compacting the pelvis, double extension of the spine/hip and a vertical, long femur. Accompanying extensive soft-tissue adaptations were changes in relative muscle volume, moment arms and, for some muscles, function. These changes improved energy efficiency of human bipedal walking and (long distance) running, although at the expense of maximum power, characteristic for activities such as tree climbing and sprinting. Spring mechanisms (for storage and release of elastic energy) of the iliopsoas,  hamstrings and triceps surae help power this efficiency of human walking and running. Strains and overuse injuries of the bi-articular triceps surae and particularly the biceps femoris indicate activities such as sprinting approach or exceed the safety factor of these springs. Conversely, the rarity of iliopsoas strains or overuse injuries may attest for the efficiency of the pulley mechanism at the femoral head and the larger safety factor of mono-articular versus bi-articular muscles. Similarly, the strongest hip extensor, the mono-articular gluteus maximus, is virtually injury-free.Thus, we find a trade-off between elastic energy efficiency during steady preferred speed running and acceleration as required for sprinting. Tendons for effective elastic energy saving must operate with low safety factors, i.e. they are relatively slender tendons, but for these tendons rapid acceleration is simply not feasible or safe . This coDespite the high loads that occur with locomotion, and excluding the hamstrings and gluteus medius, overuse injuries of muscles and tendons around the hip are quite rare. However, these high loads do create problems with dehiscence after surgical repair of tendons around the hip. Muscle preserving surgical approaches, aiming to avoid tenotomy altogether, are used increasingly, but whether all tendon insertions around the hip are really preserved has to date only been shown for the abductors, not the external rotators .Finally, operations such as trochanteric bursectomy and lengthening of the iliotibial tract are now performed endoscopically. In the field of soft-tissue hip endoscopy, surgeons may learn from their knee and shoulder colleagues. For example, randomized trials (RCT) of operative versus conservative , or evenNone declared.


To improve the availability of contraceptive supplies in Pakistan, the USAID|DELIVER Project worked with the Government of Pakistan (GoP) to develop a national web-based logistics management information system (LMIS), at all tiers of the supply chain. The LMIS automates the collection of data for contraceptives, tuberculosis, and vaccine products. The project also trains users in the skills needed to upload data, and orientates senior staff on the basic aspects of the system to ensure their support.To ensure the sustainability of LMIS training, the project developed a cadre of master trainers from government departments at the federal, provincial, and district levels. These trainers monitor the system and conduct roll out training. At each supply chain level, LMIS operators were also chosen to compile and upload data every month. Union council level staff were trained in paper-based reporting. The project provided training manuals, CDs, practical exercises, charts, and job aids to participants.The project trained 100 master trainers from all four provinces and three regions of Pakistan. Those master trainers, carefully selected from among qualified GoP staff, trained more than 2,000 LMIS users within health and population welfare departments. These operators enter data from federal, provincial, and district levels and from designated data entry clusters at the sub-district level. The participants’ level of understanding of the LMIS was measured through tests before and after the courses. Results showed significant and satisfactory scores for the majority of trainees. On average, the level of understanding of trainees increased 60-80 percent after the training.Securing local government commitment to ongoing capacity building and continuous monitoring was a key first step in building the human resources needed for new LMIS. We made a strategic decision to ensure sustainability by selecting the master trainers from within the GoP and developing their capacity to conduct trainings and provide supervision. Consulting with all stakeholders and working with master trainers to create province-specific training plans and materials was also important. Investing in the appropriate individuals from government departments ensured system sustainability and accuracy. Stakeholders now have timely, high quality data upon which to make critical supply chain decisions.Participants’ low level of computer literacy jeopardized the success of the training and the deployment of the LMIS. To remedy this, we added a computer orientation session and instituted on-the-job training and supervision during field visits. We will also provide quality assurance guidance and continued training to master trainers.


Fossils are indispensible in understanding the evolutionary origins of the modern fauna. Crown-group spadefoot toads (Anura: Pelobatoidea) are the best-known fossorial frog clade to inhabit arid environments, with species utilizing a characteristic bony spade on their foot for burrowing. Endemic to the Northern Hemisphere, they are distributed across the Holarctic except East Asia. Here we report a rare fossil of a crown-group spadefoot toad from the late Paleocene of Mongolia. The phylogenetic analysis using both morphological and molecular information recovered this Asian fossil inside the modern North American pelobatoid clade Scaphiopodidae. The presence of a spade and the phylogenetic position of the new fossil frog strongly support its burrowing behavior. The late Paleocene age and other information suggestive of a mild climate cast doubt on the conventional assertion that burrowing evolved as an adaptation to aridity in spadefoot toads. Temporally and geographically, the new fossil provides the earliest record of Scaphiopodidae worldwide, and the only member of the group in Asia. Quantitative biogeographic analysis suggests that Scaphiopodidae, despite originating in North America, dispersed into East Asia via Beringia in the Early Cenozoic. The absence of spadefoot toads in East Asia today is a result of extinction. Frogs, the largest modern amphibian clade with more than 6500 speciesPelobates, Spea and Scaphiopus) bear a distinct bony spade on their foot used in hindlimb burrowing. Other extant pelobatoids (Pelodytidae and Megophryidae) and some extinct species (e.g. Eopelobates), however, do not possess this spade. The homology of the spade has been questioned by molecular studies where Pelobates is more closely related to spade-less taxa than to Spea or Scaphiopus3578One example is a group of frogs called Pelobatoidea. Commonly known as spadefoot toads, they are one of the best-known examples of fossorial frogs, inhabiting the most arid environments where amphibians surviveHere we describe a spade-bearing frog from the late Paleocene of Tsagaan Khushuu, Mongolia. Its spade and other morphology strongly support it as one of the rare examples of spadefoot toads in East Asia. The new fossil species provides a valuable opportunity to better understand the evolutionary history of the spade and its associated burrowing behavior within pelobatoids, as well as revealing a cryptic history of the clade within East Asia. Combining the new fossil with other extant and extinct spadefoot toads in a phylogeny using morphological and molecular data, we aim to resolve the phylogenetic position of the new fossil, and to address 1) the homologous or homoplastic nature of the spade; 2) the relationships of the spade and its associated burrowing behavior with arid environments; and 3) the role of East Asia in the evolution of spadefoot toads.Amphibia Linnaeus, 1758.Anura Rafinesque, 1815.Pelobatoidea Bolkay, 1919.Scaphiopodidae Cope, 1865.Prospea holoserisca gen. et sp. nov.Prospea means “before the North American spadefoot toad Spea”, and holoserisca means “silk”, referring to its discovery on the ancient Silk Road.IGM 2/001 , a nearly complete specimen preserved as part and counterpart in grey sandy clay . The rocThe new fossil was discovered at the “frog quarry”, Tsagaan Khushuu, Nemegt Basin of the southern Gobi Desert, Mongolia. It is the first frog fossil from this locality. The fossil is preserved in the grey lacustrine sandy clay of the upper phase of the Naran Member, Naranbulak FormationScaphiopus, or cuneiform as in Spea.The new fossil taxon is assigned to Scaphiopodidae based on the combination of the following characters: medial fontanelle between the frontoparietals present, supraorbital flange of the frontoparietal present, squamosal unsculptured, vertebrae procoelous, lateral margin of the scaral diapophysis convex, sacrum-urostylar articulation monocondylar, bony sternum absent, tibiale and fibulare fused proximo-distally, and metatarsal prehallux (bony spade) enlarged. It is unique within Scaphiopodidae in that the spade is triangular, instead of scaphoid as in Prospea holoserisca differs from all extant pelobatoids  in having an unfused sacrum and urostyle. Within Scaphiopodidae, it differs from Spea in having a zygomatic ramus of the squamosal, and from Scaphiopus in having a frontoparietal fontenelle and lacking sculpture on the skull roof. It differs from Pelobatidae in having unfused frontoparietals and hatchet-shaped diapophyses of the sacrum, and lacking an ossified sternum and the posteromedial element of the frontoparietal. It differs from Megophryidae and Pelodytidae in having an enlarged prehallux. Compared with other fossil spadefoot toads, Prospea holoserisca differs from Macropelobates osborni in its smaller size, a relatively longer urostyle than the presacral vertebrae, and lacking sculpture on the skull roof. It differs from Eopelobates anthracinus in having a dorsal acetabulum expansion of the ilium over the ischium and an enlarged prehallux, and lacking the posteromedial element of the frontoparietal and an ossified sternum. It differs from Gobiates spinar in having procoelous presacral vertebrae, and lacking sculpture on the skull roof, free ribs and transverse processes on urostyle. It differs from Elkobatrachus brocki in having more expanded sacral diapophyses and a larger prehallux, and lacking an ossified sternum and transverse processes on the urostyle.Prospea holoserisca is a medium-sized frog, with a snout-pelvis length of 25 mm. It is much smaller than extant burrowing spadefoot toads . The ossification of carpal elements and humeral condyle .The pectoral girdle preserves the clavicle, coracoid and the most medial part of the scapula. It is aciferal, as indicated by the non-parallel clavicle and coracoid . The claossified , indicatossified . In the ossified . Among mPelobates, Spea and Scaphiopus) do not form a monophyletic clade  for 49 extant and extinct frogs, and nine genes  for 37 extant frogs. Analytical details are available in ic clade . HoweverProspea holoserisca as a crown-group pelobatoid, in a sister-group relationship with North American Spea within Scaphiopodidae   . Three fWe performed quantitative historical biogeographic reconstructions to test the basis for the disjunctive distribution between fossils and their extant relatives. The 55 MPTs from the combined phylogeny were analyzed in RASPSpea (node c) is also North American (p = 82.1%), the appearance of Prospea holoserisca in Mongolia represents a dispersal event from North America to East Asia. The East Asian Gobiates spinari and North American Elkobatrachus brocki are sister groups, the ancestral node of which (node d) has the highest probability of East Asian origin (p = 61.6%). This indicates that Gobiates spinari was endemic to East Asia, and the occurrence of Elkobatrachus brocki in North America was due to dispersal from East Asia to North America. The node leading to Macropelobates osborni is unresolved, making both dispersal and vicariance possible. Crown-group Pelobatidae (node e) are endemic to Europe, so was the fossil Pelobates dencheni.The base of Pelobatoidea  all bear the enlarged spade, whereas non-burrowing clades Megophryidae and Pelodytidae lack it. This led some morphological studies213143Pelobates) and Scaphiopodidae (Spea and Scaphiopus) are paraphyletic, but did not directly address how presence or absence of spade in fossils and their positions affect spade evolution. Our combined phylogeny confirmed the paraphyly of Pelobatidae and Scaphiopodidae, with fossil relatives representing both families. Plotting the presence of the spade on the tree  and stem pelobatids (Gobiates spinari and Macropelobates osborni) inhabited East Asia by the Early Cenozoic. The pattern of their subsequent extinctions deserves future study, but dramatic climate change in East Asia during the CenozoicThe role of East Asia in the evolution of Pelobatoidea has been long overlooked. Molecular analyses are restricted to modern taxa and thus cannot reconstruct the full biogeographic history of the clade due to their absence in East Asia today. Incorporating fossils with extant taxa and molecular data provides an important opportunity to address this problem. Our analyses demonstrate that both scaphiopodids  in East Asia. Sci. Rep.6, 19209; doi: 10.1038/srep19209 (2016).


The central event of each signaling step in biology is biomolecular recognition. Notwithstanding the importance of nucleic acids, carbohydrates, or lipids in ligand-target interactions, the effectors of most signal transduction processes are peptides. These can be fragments of proteins or stand-alone hormones, cytokines, toxins, antimicrobials, and many other types of peptides. At this point there is no good reason to classify peptides by the number of amino acid residues. We consider peptides as any polyamide  that can be made on a contemporary chemical peptide synthesizer. The limit in size is greater than the arbitrary cutoff of 50 amino acids set up by the US Food and Drug Administration . If it is assumed that conformational preferences improve the binding kinetics but only rarely thermodynamics, then the tremendous specificity of side-chain combinations of peptides over six residues in length can be even further expanded by using non-natural residues. Hundreds of appropriately protected and activated non-natural amino acid derivatives, ready for incorporation into synthetic peptides, are commercially available and indeed are frequently explored in peptide-based drug design. Importantly, chemical biology has provided both backbone and side-chain combinations for exploring an enormous chemical space and is expected to supply peptide chemists with further building blocks suitable for identifying close-to-ideal agonists and antagonists of any biologically important target.The high specificity and low toxicity of peptide drugs derive from their extremely tight binding to their targets. This is due to the large chemical space the side-chain variations of native amino acids cover. Current databases estimate the total number of valid protein-ligand binding sites at 7700  sequences or properties to overcome these valid concerns and to educate the public to dismiss or reduce the unfounded misconceptions. One of the true drawbacks of peptide drugs is the increased proteolytic instability compared to not only small molecules but also monoclonal antibody therapeutics. The Fc fragment of monoclonal antibodies reshuffle the protein to cells and peptide-Fc conjugates may also be protected from enzymatic cleavage  and the pharmacodynamics (what the drug does to the body) of peptide therapeutics warrants revisiting the importance of stability in vitro or bioavailability in vivo . In addition to these covalent modification technologies, micro- and nanoparticles further increase peptide delivery options. In most cases, as soon as a peptide drug lead is identified, research is initiated to improve its oral availability. In the latest example, mucoadhesive devices, made of carbopol, pectin and sodium methylcarboxy cellulose, in enteric coated capsules significantly improve the oral bioavailability and pharmacodynamics parameters of an existing peptide drug, salmon calcitonin  is a constant discussion topic between peptide drug developers and pharma. Peptides can rarely be absorbed by the intestinal mucosa, and thus cannot serve the appealing lifestyle drug market that includes treatments for weight-loss, smoking, erectile dysfunction, wrinkles, and baldness  that still linger over peptide-based therapeutics and delay the realization of the use of these highly active and safe therapy options Otvos, . By addrThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Pleura consists of visceral and parietal cell layers, producing a fluid, which is necessary for lubrication of the pleural space. Function of both mesothelial cell layers is necessary for the regulation of a constant pleural fluid volume and composition to facilitate lung movement during breathing. Recent studies have demonstrated that pleural mesothelial cells show a distinct expression pattern of tight junction proteins which are known to ubiquitously determine paracellular permeability. Most tight junction proteins provide a sealing function to epithelia, but some have been shown to have a paracellular channel function or ambiguous properties. Here we provide an in-depth review of the current knowledge concerning specific functional contribution of these proteins determining transport and barrier function of pleural mesothelium. Pleura, peritoneum and pericardium are squamous epithelia of mesothelial origin, which line lungs, chest cavity, abdomen, and heart, respectively. Pleura can be divided in the pleura visceralis or pleura pulmonalis covering lungs, and pleura parietalis covering the ribs. Both are delimitated by a single layer of epithelial cells which attach to a lamina propria, and have different functions regarding transport and barrier properties. Between the two layers, the pleura cavity is located Figure . The plegate function describing the role for paracellular permeability, but also a fence function which is a prerequisite for polarity of the cells, as it delimits diffusion of basolateral and apically located integral membrane molecules to the opposite membrane compartment, respectively , and transmesothelial resistance (mR) have been reported. The experiments revealed differences concerning absolute values, which might be attributed to different specimens and preparative protocols. However, these differences were rather marginal and in comparison with studies focusing on established epithelial models of kidney and intestine , typically located in the apical membrane. Application of ouabain and amiloride had different effects on human parietal pleura. Whereas in the caudal region, an increase of transmesothelial resistance was reported, in the cranial and mediastinal pleura no significant ouabain effect was observed  and exchangers, which also contribute to vectorial transport. ENaC is the limiting factor for epithelial sodium absorption in a variety of tissues and organs, including the distal nephron and colon epithelium  in visceral and parietal pleura of rabbit and sheep, and human primary cells  sealing tight junction proteins, (ii) claudins mediating paracellular permeability and (iii) claudins with ambiguous function. Among the claudins detected in pleura mesothelium, claudin-1, -3, and -5 belong to the first group, whereas claudin-2 belongs to the second, and claudin-7 to the third group.Claudin-1-deficient mice die within hours after birth because of dehydration. These animals show a severe weight loss due to evaporation of water through the skin , which explains e.g., the pathomechanism of inflammatory bowel diseases , and an opening of the paracellular barrier (Ma et al., These alterations in claudin expression are in contrast to findings reported in analyses of pleura cancer and mesothelioma, which show an alteration of claudin-4. In this context, Claudin 4 was identified to be an important marker for carcinoma vs. mesothelioma diagnosis in pleural and peritoneal biopsies and effusions, as it is detected in metastatic tumor cells but not in benign forms of mesotheliomas (Facchetti et al., Transport and barrier function of pleura mesothelium indicate typical epithelial characteristics. Expression of the major sealing tight junction proteins-1, -3, and -5 indicate a physiological role of the mesothelial barrier function for pleural liquid formation. Moreover, the effects observed in inflamed pleura, namely an induction of the paracellular pore claudin-2 and the decrease of tightening tight junction proteins are in accordance with regulatory mechanisms observed in inflamed epithelia, as shown e.g., for inflammatory bowel diseases. These findings may contribute to future therapeutic and preventive approaches regarding mesothelia.Alexander G. Markov and Salah Amasheh conceived the review, conducted literature survey and wrote the review.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Nowadays, consumers in developed countries demand food products of high-quality, which are easy-to-handle, safe, and with natural flavor and color, as well as with an extended shelf life . One of In this respect, application of new discoveries in health-promoting food manufacture has been an intriguing and exciting topic of major public concern, while at the same time it confers multiple advantages in the industrial sector. In response to demands from increasingly health conscious consumers, the global new trend focuses on foods not only with superior sensory appeal but also of improved nutritional attributes. Current innovations in food production have resulted in the development of novel products with specific functional ingredients, reduction or removal of undesirable components, modification of food compositions, and overall improved quality and safety.2 photocatalysis treatment were explored. Results revealed that the UV-vis absorption and the fluorescence intensity increased with higher photocatalytic power. SPI-dextran conjugate was successfully formed by TiO2 photocatalysis treatment. Likewise, the effect of chitosan coating with cinnamon oil on the physiological attributes and preservation quality of China jujube fruits during storage was investigated. This investigation revealed that the complex coating of chitosan and cinnamon oil could directly control disease decay and maintained the good sensory acceptability of jujube fruits. Moreover, during storage time, the treatment of chitosan-oil coating might maintain the quality attributes and induce the defense reaction system of jujube fruits.One of the main objectives of this special issue was to provide a number of documents to summarize new inventions, developments, and ideas in the most recent innovation opportunities and technological achievements in the production of foods with potent beneficial effects. In this context, the structural characteristics and antioxidant activities of soy protein isolate (SPI) dextran conjugates obtained by TiOA universal approach based on “omics” technologies for the quality control of food was fully discussed. Up-to-date technologies based on digital information systems such as web platforms and smartphone applications, can facilitate the adoption of molecular labelling. In this respect, recent smartphone “apps” are becoming a powerful tool to promote the consumption of high-quality foodstuffs and in particular the consumption of those food items able to prevent diseases –6. Such An overview of current and new approaches in genetically modified organisms detection was also assumed. Furthermore, the benefits and drawbacks of such methodologies were discussed, too. In addition, a protocol was validated and determined to be suitable for practical use in monitoring and identifying genetically modified rice. The results indicated that the established methodology is convenient, rapid, and of low-cost for routine detection of genetically modified rice.Finally, nanotechnology has proven its competence in almost all possible fields to food and agricultural systems –9. HenceYiannis KourkoutasNikos ChorianopoulosAspasia NisiotouVasilis P. ValdramidisKimon A. G. Karatzas


Clinical Significance. The present clinical report shows that the use of a split-framework reduced the risk of loss of the posterior implants or screws loosening with acceptable patient comfort over the period of a year. The split-framework might have compensated for the mandibular flexure during functional activities.During oral rehabilitation of an edentulous patient with an implant-supported prosthesis, mandibular flexure must be considered an important biomechanical factor when planning the metal framework design, especially if implants are installed posterior to the interforaminal region. When an edentulous mandible is restored with a fixed implant-supported prosthesis connected by a fixed full-arch framework, mandibular flexure may cause needless stress in the overall restorative system and lead to screw loosening, poor fit of prosthesis, loss of the posterior implant, and patient's discomfort due to deformation properties of the mandible during functional movements. The use of a split-framework could decrease the stress with a precise and passive fit on the implants and restore a more natural functional condition of the mandible, helping in the longevity of the prosthesis. Therefore, the present clinical report describes the oral rehabilitation of an edentulous patient by a mandibular fixed implant-supported prosthesis with a split-framework to compensate for mandibular flexure. The oral rehabilitation of an edentulous patient treated with a fixed implant-supported prosthesis using appropriate biomechanical and prosthetic principles has been a goal in oral implant research for the last decade . With thA common treatment for an edentulous mandible is the installation of implants in the interforaminal region and a full-arch fixed implant-supported prosthesis with cantilever distal extensions , 4. HoweAlthough it is an alternative, the use of an implant fixed restoration with a continuous and rigid framework can create dangerous stress at the bone/implant interface and at the prosthetic superstructure due to the deformation properties of the mandible, which can occur during functional and parafunctional loads , 9. MandDuring functional activities, mandibular flexure should be considered an important biomechanical factor in the design of a partial or complete fixed implant-supported prosthesis in the mandible with dental implants –16. In nTherefore, for better longevity and outcomes of implant-related prostheses, it is important to reduce the effects of mandibular flexure , 16. SevA 51-year-old man was referred to the Araraquara Dental School, UNESP, Universidade Estadual Paulista, Araraquara, SP, Brazil, for assessment and manufacture of a mandibular fixed implant-supported prosthesis. The main complaint was mobility and pain of the remaining teeth in the mandible. An intraoral examination was performed and the presence of caries in some teeth was verified, as well as chronic periodontitis in all remaining teeth . The patThe proposed treatment for the mandible was extraction of the remaining teeth, installation of six implants, and immediate loading with a mandibular fixed implant-supported prosthesis. After the extraction of the remaining teeth, four implants were installed in the posterior mandible and two implants were installed in the interforaminal region . Six minicone abutments  were also installed and the impression was performed using impression coping  splinted with polymethyl methacrylate (PMMA) resin   and polyFinally, the definitive casts were mounted in a semiadjustable articulator  and artificial acrylic resin teeth  were set and evaluated in the patient. A framework was manufactured using a castable coping of abutments and Ni-Cr alloy .Next, a simplified technique for fixed implant-supported prosthesis was used for the wax teeth and framework trials . In thisAfter intraoral assessment, the framework within the teeth was included in a flask  with plaster type III . The wax was removed and the framework was split into three sections with a carborundum disc . Heat-poAchieving lower stress in an implant-supported restorative system is one of the main goals of implant treatment from a mechanical point of view. In the present case, the framework was split in three pieces Figures  and 5 beDuring oral rehabilitation of edentulous patients with mandibular fixed implant-supported prostheses, mandibular flexure could be affected by two important factors: 1) position of the implants and (2) typology of the prosthetic structure  position. Also, tFurthermore, the mandibular flexure must be considered an important factor because it could contribute to discomfort related to the patients' rehabilitation with a mandibular fixed implant-supported prosthesis during function . In thisA study of stress analysis has shown that frameworks constructed with a precise and passive fit induce significantly smaller amounts of stress on the implant  and thisSectioning the prostheses into two or three pieces , 18 has The contraction of the lateral pterygoid muscle is the most important factor causing mandibular deformation during function and four patterns of jaw deformation were postulated: symphyseal bending, dorsoventral shear, corporal rotation, and anteroposterior shear . SplittiConsidering that the modulus of elasticity of the PMMA resin is lower than the framework of Ni-Cr and due to the sectioning of the framework, the PMMA resin could suffer deformation during mandibular flexure, decreasing stress. Furthermore, because the framework was split into three pieces, it could be suggested that the stress during mandibular flexure is lower when compared with an implant-supported prosthesis with a fixed full-arch framework.In the present case, the installation of posterior implants was used to decrease the lever arm, allowing greater posterior extension and increased occlusion scheme in the mandibular fixed implant-supported prosthesis, which provided a better distribution of occlusal forces and increased the prosthesis stability. In addition, the precise and passive fit of the split-framework and properties of PMMA resin could have reduced the effect of the mandibular flexure damage in the bone-implant interface in the posterior implants, which may help to increase the longevity of the prosthesis.The use of a mandibular fixed implanted-supported prosthesis with a split-framework is a good alternative to compensate for mandibular flexure, providing good stability and retention of the implant-supported prosthesis without loss of the posterior implant or screw loosening with acceptable patient comfort during a period of one year.


In this perspective article, we question how well model organisms, the ones that are easy to cultivate in the laboratory and that show robust growth and biomass accumulation, reflect the dynamics and interactions of microbial communities observed in nature. Today’s -omics toolbox allows assessing the genomic potential of microbes in natural environments in a high-throughput fashion and at a strain-level resolution. However, understanding of the details of microbial activities and of the mechanistic bases of community function still requires experimental validation in simplified and fully controlled systems such as synthetic communities. We have studied methane utilization in Lake Washington sediment for a few decades and have identified a number of species genetically equipped for this activity. We have also identified co-occurring satellite species that appear to form functional communities together with the methanotrophs. Here, we compare experimental findings from manipulation of natural communities involved in metabolism of methane in this niche with findings from manipulation of synthetic communities assembled in the laboratory of species originating from the same study site, from very simple (two-species) to rather complex (50-species) synthetic communities. We observe some common trends in community dynamics between the two types of communities, toward representation of specific functional guilds. However, we also identify strong discrepancies between the dominant methane oxidizers in synthetic communities compared to natural communities, under similar incubation conditions. These findings highlight the challenges that exist in using the synthetic community approach to modeling dynamics and species interactions in natural communities. For centuries, Biology has relied on model organisms for understanding the details of metabolism, regulation, evolution trends, etc. For example, rats, mice, nematode worms and yeast are all used as models for understanding complex metabolism and regulation in humans . MicrobiMethane oxidation is an important environmental process that mitigates release of large quantities of methane, mostly generated biogenically, via degradation of complex organic matter . This prMethylomonas (gammaproteobacteria) and Methylosinus  of major players, as observed at pure culture level, compared to activities/conditions approximating environmental settings. The existence of such discrepancies would have major implications for the selection of laboratory models and the experimental conditions. It would affect not only how we interpret the data on their performance, but also how we scale up these findings to the level of predicting and modeling global elemental cycles. Ultimately, we question whether our model choices and their manipulation in simplified laboratory settings allow for realistic interpretation of microbial activities in natural environmental settings.Figure 1), to address the discrepancies between the performance of natural communities in semi-in situ conditions and laboratory performance of pure culture isolates. Even though all 50 organisms originated from Lake Washington sediment, we did not follow any specific design for community structure, assuming that species that thrive in the specific incubation conditions that we apply would increase in their abundance and species that are not fit for these conditions would decrease in their abundance. Live cultures were mixed together in similar cell counts and were incubated for several weeks, with periodic transfers and dilutions, as previously described (2), low methane/high oxygen , and high methane/high oxygen . While the first two conditions mimicked gas concentrations in the opposing parts of methane and oxygen gradients in the natural lake sediment, the third condition represented a typical laboratory setting. We addressed two main questions: (i) whether Methylomonas and Methylosinus would outperform Methylobacter and Methylosarcina, to reflect their robust performance in the laboratory, and (ii) whether species other than Methylophilaceae, Flavobacteriales or Burkholderiales would persist in methane-fed communities, also based on laboratory performance of the cultivated species. In each of the communities, rapid loss of species complexity was observed after a few days of incubation, as previously observed for natural communities of high complexity  while methanotrophs of the family Methylocystaceae were undetectable. However, significant differences compared to natural community dynamics were uncovered in terms of the dominant methanotrophs. While Methylobacter species were found as dominant under the HL condition in natural samples . The dynamics of the Methylosarcina population also differed from the ones previously observed in natural communities. While Methylosarcina was reported to outperform Methylobacter under the HH condition .We assembled synthetic communities of 10 methanotrophs, 36 non-methanotrophic methylotrophs, and 4 non-methylotrophic heterotrophs . The results from these incubations clearly demonstrate that the performance/fitness of the three model organisms, as pure cultures, did not correlate well with their performance/fitness as parts of synthetic communities, even when simple two- to three-species communities were considered . In turn, their performance/fitness as parts of synthetic communities did not correlate well with the performance/fitness of their closely related counterparts as parts of natural communities . However, performance/fitness of the simple (3-species) and the complex (50 species) synthetic communities showed some agreement . Thus, we conclude that synthetic communities, at least as applied to methane-oxidizing communities and in the conditions used, appear to behave differently from the natural communities. These observations question, more generally, our reliance on data from laboratory manipulations for global predictions as related to microbe-mediated environmental processes.We next measured growth curves for pure cultures of three methanotroph species, Methylomonas spp., hardly seen in natural communities, showing robust performance, in agreement with their documented growth characteristics  The strains that we successfully isolated in pure cultures poorly reflect strains that are active in the natural habitat. However, we do have evidence of their close relatedness at the genomic level (Microbial communities involved in methane metabolism were used here as one example of a functional microbial assemblage involved into a specific biogeochemical process. In microbial ecology, and in ecology in general, fitness and performance of individual species are often considered as predictors of success in natural communities. However, the necessity of measuring performance in natural settings has been advocated . We hereeristics . In factsediment , and we ic level , understLC and ZY designed the experiments, ZY carried out experiments, SK carried out flow cytometric counting, DB carried out iTag data clustering. ZY and DB prepared figures. LC, ZY, SK, and DB wrote the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Pancreatic tumors are challenging diseases. Pancreatic adenocarcinoma (PDAC), in particular, is associated with significant morbidity and mortality. Another group of exocrine tumors, intraductal papillary mucinous neoplasia (IPMNs), represents the paradigm of progression of malignancy and their connection and differentiation with respect to pancreatic ductal adenocarcinoma (PDAC) which is still complicated. In this special issue, we would like to offer readers an overview of some important aspects for the two most representative exocrine tumors as IPMN and PDAC. The original communications within this special issue fall into four different categories: pancreatic surgery, management of IPMN patients, treatment of pancreatic tumors, and, last but not least, some important aspects of basic science in PDAC.Surgery. Curative resection is considered the only potential for cure in pancreatic cancer. Complete macroscopic tumor resection is perhaps the most relevant predictor of long-term survival in PDAC. Locally advanced pancreatic tumors can involve vascular structures and adjacent organs, and thus vein resections and even resections of additional organs may be needed to achieve the goal. Improving surgical methods to achieve this goal is crucial in the treatment of this disease.In pancreatic surgery, postoperative pancreatic fistula (POPF) remains the most challenging complication after resections, whether pancreatoduodenectomy or distal. POPFs are contributing significantly to prolonged hospitalization and mortality. Several studies using various anastomotic and sealing techniques have been studied to reduce the amount of POPFs. Some previous investigations have shown that pancreatic trauma and the following inflammation are preceding postoperative complications and they should be avoided. Patients with normal, acinar-cell rich pancreas are in higher risk to develop POPF. One promising technique for pancreatoduodenectomy is the Finnish binding pancreaticojejunal anastomosis (FBPJ), where the pancreatic trauma is minimized by avoiding sutures running through the pancreatic tissue. The preliminary previous studies with this technique have shown reduced amount of POPF after pancreatoduodenectomy.IPMN Management. Intraductal papillary mucinous neoplasms of the pancreas (IPMNs) are a high prevalence neoplasm of the pancreas. IPMNs can progress from adenoma to invasive cancer through a process very similar to the one of the colonic polyps. At the moment the management of pancreatic IPMN is suggested by the Guidelines of the International Association of Pancreatology and by the European Guidelines for Cystic Tumors of the Pancreas. However, till now, the available evidence about the diagnosis and treatment of those tumors is quite low and the clinical decisions are made on the basis of expert consensus (more than guidelines) and local expertise. Even though IPMNs represent in one side an opportunity to prevent pancreas cancer (through an early detection and treatment of precancerous lesions), considering the high risk associated with pancreatic surgery, there is a potential risk to overtreat patients that might never develop cancer. Even the decision making in the intraoperative management of IPMNs is complicated: the extent of resection, the role of parenchyma sparing procedure, and the role and significance of margins analysis are argument under investigations and have not been yet defined.To make the overall picture even more complicated, the accuracy of the current imaging modalities is reported very low even in high volume centers. In a recent series the overall accuracy in defining preoperative diagnosis in cystic tumors of the pancreas was inferior to 70% and even the use of endoscopic ultrasound plus FNA was not able to increase the results. More large studies are needed in order to better understand the natural history of these tumors, to discriminate the ones that can progress to cancer from the ones with low aggressive behavior. At the same time, new insight into the field of diagnostic is necessary in order to increase the accuracy of imaging modalities. For the reasons mentioned above and for the tremendously high prevalence, IPMNs represent today maybe the most challenging area of interest in pancreatology, a great opportunity to reduce the pancreas cancer mortality, but also one of the most dangerous clinical areas.Pancreatic Cancer Treatments. Pancreatic adenocarcinoma is one of the most deadly cancers, with an overall 5-year survival of 5%. Complete surgical resection provides the only chance for cure. Unfortunately, most patients are diagnosed with locally advanced or metastatic disease. Chemotherapy, with and without radiation, has been investigated in both neoadjuvant and postoperative settings. At present, multimodality therapy seems to be the future direction. However, the sequence of surgery, chemotherapy, and radiation remains to be determined. In the review of this special issue, the authors examined available data on neoadjuvant treatment in resectable patients and in patients with borderline resectable or locally advanced disease.Of course, the need for new therapies is undisputed. One of the latest local treatments is high-intensity focused ultrasound (HIFU), a noninvasive and safe technique to ablate solid tumors. In this special issue, the authors have reviewed all 3022 cases, described in the literature, with respect to safety and efficacy.Basic Science of PDAC. In the papers published in this special issue, the authors treated three molecular aspects regarding the PDAC: indicator tryptase, ATP-binding cassette (ABC) transporters, and micro-RNA (miRNA) expression. These molecules are involved in the progression, chemoresistance, and survival of PDAC patients, respectively. In particular, M. Ammendola et al. have shown the role of tryptase in PDAC which is associated with mast cells to increase the microvascular density (MVD) in tissue PDAC. This could play an important role in vascularization, the absorption of drugs, and chemoresistance of PDAC. In fact, drug chemoresistance of PDAC cells is recognized as the primary cause of failure of chemotherapy. Although biochemical behaviors, including low drug concentration in the tumor, may contribute to clinical resistance, different types of molecules, including ATP-binding cassette transporters, are the main actors in the extrusion of drugs in different tumors. In particular, some single nucleotide polymorphisms (SNPs) of the three most important family genes of ABC  are associated with a lower risk of developing pancreatic cancer and an increased sensitivity to gemcitabine than other haplotypes. Finally, the most important epigenetic factors, such as miRNAs, were confirmed to be “micromolecules,” regulating “the great effects.” Their deregulation modulates several important processes in PDAC, including differentiation, tumor progression, and epithelial-mesenchymal transition (EMT). Nevertheless, miRNAs affect overall survival and chemoresistance of PDAC patients. Aberrant expression of three most important miRNAs  is strongly associated with PDAC, IPMN, and nonmalignant lesions, respectively.Niccola FunelNiccola FunelMarco Del ChiaroMarco Del ChiaroDjuna L. CahenDjuna L. CahenJohanna LaukkarinenJohanna Laukkarinen


The principal feature of Parkinson’s disease (PD) is the impaired ability to acquire and express habitual-automatic actions due to the loss of dopamine in the dorsolateral striatum, the region of the basal ganglia associated with the control of habitual behavior. Dopamine replacement therapy (DRT) compensates for the lack of dopamine, representing the standard treatment for different motor symptoms of PD . On the other hand, rehabilitation treatments, exploiting the use of cognitive strategies, feedbacks and external cues, permit to “learn to bypass” the defective basal ganglia  allowing the patients to perform correct movements under executive-volitional control. Therefore, DRT and rehabilitation seem to be two complementary and synergistic approaches. Learning and reward are central in rehabilitation: both of these mechanisms are the basis for the success of any rehabilitative treatment. Anyway, it is known that “learning resources” and reward could be negatively influenced from dopaminergic drugs. Furthermore, DRT causes different well-known complications: among these, dyskinesias, motor fluctuations, and dopamine dysregulation syndrome (DDS) are intimately linked with the alteration in the learning and reward mechanisms and could impact seriously on the rehabilitative outcomes. These considerations highlight the need for careful titration of DRT to produce the desired improvement in motor symptoms while minimizing the associated detrimental effects. This is important in order to maximize the motor re-learning based on repetition, reward and practice during rehabilitation. In this scenario, we review the knowledge concerning the interactions between DRT, learning and reward, examine the most impactful DRT side effects and provide suggestions for optimizing rehabilitation in PD. Parkinson’s disease (PD) is a progressive neurodegenerative disorder clinically dominated by bradykinesia, rigidity and resting tremor. The neuropathological hallmark of PD is the dopaminergic neuronal loss in the pars compacta of the substantia nigra ; MY supported by an NHMRC Fellowship Award #APP1021973.


Objective. Craniopharyngioma is a rare tumour, and, consequently, acute clinical presentation and diagnosis, during pregnancy, of this pathology are quite difficult to find. Only few cases are reported in the literature, and no one describes these two conditions in association. Methods. We report a particular case of craniopharyngioma presenting both of the above conditions. Results. The patient was successfully operated with endoscopic technique. Conclusions. Rare and difficult cases, created by the superposition of different clinical conditions, need multidisciplinary management, with collaboration, integration, and cooperation between different medical specialists. Craniopharyngioma is a rare tumour, with incidence of 0,13 cases per 100,000 people/year . The terAcute clinical presentation of craniopharyngioma—consisting of sudden headache, nausea, vomiting, cranial nerves palsy, decrease in visual acuity, diabetes insipidus, fever, or reduced level of consciousness—is very unusual, about 13% of all cases . Within Even more rarely craniopharyngiomas manifest themselves with acute clinical presentation during pregnancy; from 1935 to 2013, 8 cases of craniopharyngioma during pregnancy were described in the international literature  19–24]..24].This report describes a particular case of craniopharyngioma that presents both of the above peculiarities; despite the difficulties caused by intratumoral haemorrhage and pregnancy, this tumour was treated with endoscopic mini-invasive surgery, resulting in a good and early resolution of the mother's new symptoms without negative consequences for the newborn.The patient, a 32-year-old woman, became pregnant for the first time in her life. At the 30 weeks + 1 mark of a till-then-normal pregnancy, she presented a sharp bilateral decline in visual acuity. A careful study of her clinical history only noted obesity and Hashimoto's thyroiditis treated with chronic hormone replacement. Then she was assessed by the ophthalmologist: a visual field examination  documentThe international literature counts only few cases of craniopharyngiomas in pregnancy and equally few of intralesional haemorrhage cases in this kind of tumours.As showed in As shown in The case we report is of particular relevance because it is the first to include both of these rarely associated clinical features. Such combination requires a multidisciplinary assessment to allow choosing the most suitable treatment from different specialistic points of view: neurosurgical, neuroradiological, endocrinological, obstetrical, gynaecological, otolaryngological, and ophthalmological.The role of the first specialist observing the patient is crucial: his task is to correctly identify the location of the problem, in order to set an appropriate diagnostic and therapeutic plan. In the case we report, the first specialist to assess the patient was the ophthalmologist. Bitemporal hemianopia or temporal field cuts in the examination of the visual field are often suggestive of expansive lesions near the optic chiasm and sellar region. A suspicion of such nature needs neuroradiological evidence, obtainable by MRI. In this case, since the patient was pregnant, MRI was performed without contrast: it showed the presence of an extra-axial lesion in the sellar and suprasellar regions. As described by Jagannathan et al., there are many diseases that can develop in these anatomical sites: pituitary adenomas, meningiomas, metastases, abscesses, aneurysms, pituitary apoplexy, and Rathke's cleft cyst in the sellar region and aneurysms, teratomas, hypothalamic gliomas, meningiomas, and epidermoid and dermoid cysts in the suprasellar regions . In the The choice of endoscopic treatment was based on the great benefits reported by the international literature during the last years –38: miniIn this case, a patient with a delicate endocrinological balance underwent 2 surgical procedures in few hours: use of endoscopic minimally invasive technique reduced the consequences of this particular surgical stress. Reduced recovery days and early ability in taking care of the newborn also resulted in the patient's more positive psychological reaction to her own disease.In our opinion, this case represents another excellent demonstration of the versatility of the endoscopic technique, which can be used in complex clinical conditions and considered a gold standard in the surgery of the sellar and paraphrase regions.The role of the various specialists remains important during follow-up of the patient: the ENT surgeon endoscopically checks for good repair of the wound; the neuroradiologist carries out the necessary radiological postoperative scans (CT in the early postoperative period and MRI 3 months later); the endocrinologist checks the hormonal balance and sets adequate hormone replacement; the ophthalmologist carries out field examinations in the postoperative period. Therefore, the collaboration remains critical among these different medical figures during follow-up.We report what, to the best of our knowledge, is the first case in the literature in which two rare features of craniopharyngiomas overlapped at the onset; such synergistic coexistence created a clinical condition difficult to diagnose and manage.In this particular situation, once diagnosis of sellar lesion had been obtained, all medical and surgical treatments undertaken were found to be necessary and, in particular, endoscopic minimally invasive surgery was considered the first choice. In our opinion this technique represents the gold standard in surgical approach to sellar and parasellar regions and is indispensable in cases like the reported one.Rare and difficult cases, created by the overlapping of different clinical conditions, need multidisciplinary management, with collaboration and cooperation between many medical specialists: careful preoperative planning, minimally invasive surgery with less possible complications, and adequate follow-up are obtained only with close support and collaboration among all specialists involved.


Injury to the sternocostal synchondrosis of the first rib is quite rare. We report one such case in a 50-year-old man with nonunion of the first sternocostal synchondrosis accompanied by synovitis of the sternoclavicular joint. He first underwent arthroscopic surgery of the left sternoclavicular joint. Postoperatively, the patient's symptoms decreased by half, but another pain and crepitus at the inferior lateral portion of the sternoclavicular joint developed. Since MRI and functional CT reexaminations revealed nonunion of the first sternocostal synchondrosis, resection arthroplasty of the first sternocostal joint was performed. This resulted in immediate resolution of the symptoms. At 2-year follow-up, his symptoms disappeared entirely with no limited range of motion of the shoulder. The most common site of first rib fracture is the middle-third of the diaphysis , becauseA 50-year-old, right-hand-dominant man presented with left upper thoracic pain upon shoulder elevation. One year earlier, he was involved in a head-on car collision, which resulted in acute pain in the upper half of the body when moving his left arm forward. He was seated in the front right (driver's) seat and wearing a three-point seatbelt at the time of the accident. Cervical spine sprain and left shoulder contusion were diagnosed at an emergency hospital, and although he was treated with medication and rehabilitation, his symptoms did not improve. Physical examination of the left glenohumeral joint revealed no limited range of motion, muscle weakness, or signs of instability, but tenderness was noted around the sternoclavicular joint. Crepitus and severe pain in the left upper thorax occurred during moving the left shoulder downward from 80 to 70 degrees in flexion. A lower brachial plexus injury was also suspected because of a sensory disturbance in the C8 cervical root area and weak grip . Although initial examination of the sternoclavicular joint on plain radiography, computed tomography (CT), and magnetic resonance imaging (MRI) revealed no obvious abnormalities, injection of corticosteroid and local anesthetic into the sternoclavicular joint temporally reduced the pain. As we assumed that his symptoms were caused by injury to the sternoclavicular joint disc accompanied by synovitis, we performed arthroscopic surgery of the left sternoclavicular joint. Because arthroscopic findings demonstrated synovitis and partial tear of the intra-articular disc of the left sternoclavicular joint , synovecThe patient was treated conservatively with corticosteroid injection for 4 months, but his symptoms persisted. We, therefore, performed resection arthroplasty for nonunion of the first rib synchondrosis. Intraoperatively, subluxation of the first rib was observed upon flexion of the left upper arm. Dissection of the subclavius muscle and costoclavicular ligaments from the left clavicle improved the abnormal mobility of the first rib. Both cartilage surfaces of the nonunion site were irregular, and both the sternum and the first rib showed degeneration. The medial end of the first rib was removed until no contact with the sternum was obtained. Postoperatively, the pain and crepitus in the left upper thorax disappeared entirely, with no limited range of motion of the shoulder or recurrence of symptoms noted at the 2-year follow-up.Injury to the first costochondral joint is relatively uncommon compared with injury to lower costochondral joints. To our knowledge, only a few cases of injury to the first sternocostal synchondrosis have been reported , 8. One The mechanism of first rib injury in car collisions is thought to be violent contraction of the scalene muscles brought about by the sudden forward movement of the head and neck and, in a car collision, consequent sudden arrest by the seatbelt , 9. AnotThe patient was first diagnosed as having a disc injury accompanied by synovitis of the sternoclavicular joint for which he underwent arthroscopic partial discectomy and synovectomy of the left sternoclavicular joint. His symptoms immediately improved by half. Based on this observation, the synovitis could have been secondary to the instability due to nonunion of the first sternocostal synchondrosis, since the clavicle, manubrium, and the first costal cartilage constitute the joint's articulation through being connected by the intra-articular ligament , 13. SomConservative therapies, such as medication, rest, and rehabilitation, are recommended as initial treatments for first rib injury. When conservative treatment is not successful, resection arthroplasty for first rib nonunion is effective for relieving symptoms –18. In tIn summary, physicians should pay careful attention to injury of the first costochondral joint when a patient presents with persistent pain in the sternoclavicular joint after a head-on car collision. MR fat suppression imaging and/or dynamic CT evaluation in different arm positions can provide critical information for precisely diagnosing sternocostal synchondrosis injury.


Hyperinsulinemic hypoglicemia with severe neuroglycopenic symptoms has beenidentified as a late and rare complication in patients submitted to Roux-en-Ygastric bypass. However, the potential gravity of its manifestations requireseffective treatment of this condition. The absence of treatment makes it necessaryto develop more effective clinical or surgical methods. To present one surgical option to revisional surgery in the treatment ofhyperinsulinemic hypoglicemia The procedure consists in reconstituting alimentary transit through the duodenumand proximal jejunum, while keeping the restrictive part of the gastric bypass. Asan additional strategy to maintain weight loss, is realized gastric fundusresection, aiming to suppress ghrelin production more effectively.  It was used in three patients with successful results in one year of follow-up. The procedure to reconstruct the food transit through the duodenum and proximaljejunum, keeping the restrictive component of gastric bypass in the treatment ofhyperinsulinemic hypoglycemia showed good initial results and validated itsapplication in other cases with this indication. A syndrome called non-insulinoma pancreatogenous hyperinsulinemichypoglycemia, syndrome - NIPHS includes neuroglycopenic symptoms such as cognitiveimpairment, behavioral changes, confusion, depression, sweating, weakness, dizziness,and, if severe hypoglycemia, generalized or focal seizures and coma, associated withdocumented hypoglycemia,,,Patients with such documented postprandial symptoms should be investigated in order torule out other causes of hyperinsulinemic hypoglycemia, as the factitious (byadministration of exogenous insulin or similar agents) and by insulinoma, beingessential value the presence of normal or increased dosages of peptide-C and proinsulinin addition to the disposal by imaging of focal pancreatic lesions, to confirm NIPHS asthe causeDespite the affordable diagnosis, there is no consensus on the best treatment of thesyndrome in the postoperative bariatric surgery, specifically gastric bypass. Initialtherapy to be instituted, consisting of dietary and behavioral measures, has modestresponse, even when added the use of medications such as acarbose,Treatments aimed at restoring the intestinal transit, as the reversal of prior bariatricsurgery or revision to vertical gastrectomy showed good result in the resolution ofepisodes of reactive hypoglycemia, especially in cases where there was good response topreoperative nutrition by gastrostomy tactic that simulates the reconstitution effect ofthe transit through the duodenum and proximal jejunum. This is probably due to therelease of anti-incretinic factors for these portions of the digestive tract whenstimulatedEven with good response, complete reversal of gastric bypass in Roux-en-Y results in theundesired effect of returning to the original anatomy, which can lead to full regainedthe weight lost and returning the preoperative comorbidities. The review for verticalgastrectomy, while providing the benefits related to this technique is complex and highmorbidity rate, mainly related to the occurrence of gastric fistula.The objective of this paper is to present proposal for revisional surgery for thetreatment of NIPHS through new surgical procedure, technically simpler than the existingalternatives, based on the pathophysiology of the condition and maintenance of weightloss.The study was approved by the Ethics Committee on Research of the Hospital Santa Casa,Curitiba, PR, Brazil. Patients signed the free and informed consent form for thesurgery.The procedure consisted of laparoscopic access followed by release of supramesocolicadhesions. After identification of the bypassed stomach, it was held release of thegreater curvature vessels with ultrasonic scalpel, followed by resection of thebackground and part of the gastric body with endoscopic stapler, and strengtheningclamps line with manual suture.Then was proceeded the section of food loop next to enteroenteric original anastomosis,proximal to it. The distal portion of feed loop was then anastomosed laterally withgastric antrum 4 cm from the pylorus .At the Patients were fasted orally until the second day after surgery, when it was releaserestrict liquid diet and hospital discharge. It was conducted clinical and laboratoryoutpatient monitoring after 15 days, 45 days, three months and at each three months tothe end of the first year. The postoperative radiologic appearance after oral intakecontrast can be seen in The procedure was performed in three cases through laparoscopy in patients previouslyoperated for 8, 9 and 11 years. They presented before the bariatric procedurecomorbidities such as hypertension, fatty liver and dyslipidemia, with poor control andthat were solved with the initial procedure. They were three women with significantweight loss after performing the first surgical procedure .The patients had neuroglycopenic course with episodes of hypoglycemia in the latepostoperative period, about six years after the procedure. The episodes of decreasedlevel of consciousness and seizures initiated approximately 90-120 min after feeding,during which were documented capillary blood glucose of 35-45 mg/dl, which improvedafter parenteral infusion of glucose. During the etiological investigation it was foundnormality of serum C-peptide values, thus discarding the hypothesis factitioushyperinsulinemia. Glucose curve was performed from patients who showed hypoglycemia inthe second hour after administration of glucose. Aiming to differentiate betweeninsulinoma and NIPHS, was performed abdominal computed tomography with high resolutionwithout evidence of the presence of focal pancreatic lesions. The realization of dietaryand behavioral measures with nutritional and psychological support, as well as theaddition of acarbose to clinical treatment, did not result in controlling symptoms, andthe patients remained with multiple hospitalizations due to hypoglycemic events. Thus,it was proposed to carry out the surgical procedure to control the condition. Sincethere was refusal to employment pancreatic resection and the reversal of bariatricsurgery, it was proposed treatment based on the pathophysiology of secondary NIPHShyperinsulinemic hypoglycemia, jointly aiming at maintaining weight loss and resolutionof preoperative comorbidities. The three patients had total symptom improvement anddenied new episodes of hypoglycemia after revisional operation. The oral glucosetolerance tests confirmed the remission of the condition. Weight loss and resolution ofcomorbidities were held in all three cases, there was even extra weight loss in two ofthe patients. Hypoglycemia with severe clinical symptoms occurs in about 1% of patients undergoingRoux-en-Y gastric bypass and it can happen in diabetic patients or not.The main causes are the late dumping syndrome, factitious administration of insulin ororal hypoglycemic agents and NIPHS.In the late dumping syndrome or reactive hypoglycemia may occur neuroglycopenic symptomsin response to high insulin release by eating foods with high glycemic index. Oftenthere is an association with vasomotor manifestations, related to early dumping, whichwere most prevalent in symptoms. The resolution of the condition occurs with dietaryreadjustment and psychological support, without the use of pharmacological or surgicaltreatments.In NIPHS the main symptoms are neuroglycopenic (changing level of consciousness andseizures), and generally occur 2-4 h after feeding. Hypoglycemic episodes should bedocumented and are usually below 45 mg/dl.Fundamental part on the results on diabetes mellitus type 2 resolution - loss and weightmaintenance after Roux-en-Y gastric bypass -, is related to the increased secretion ofincretinic hormones, such as GIP, peptide-YY, oxyntomodulin and especially GLP 1.Treatment of NIPHS is not defined. Initially, low-carbohydrate diet could benefit;however, this therapy is ineffective. As a second alternative proposal, apply somedifferent medications as acarbose and octreotide. Drug treatment should be used in thedietary failure. In the absence of response to drug therapy, surgical therapy has beensuggested.In this case, there will be feasible and safe procedure, based on the trigger mechanismof the syndrome. The gastrectomy of the bypassed stomach aimed to be similar to thevertical gastrectomy, leaving a smaller gastric pouch and removing the orexigenicghrelin stimulus. Staying there it could represent the major factor in weightregained.The anastomosis of the feed loop to pre-pyloric antrum aims to reassume normalintestinal transit promoting change of the enteroinsular axis diminishing GIP and GLP-1and hence hyperinsulinemia. It must be considered the possibility of regain weight in this operation. In this case,after the follow-up realized, the weight regain was not a rule, occurring evenadditional weight loss of 11.17 kg and 11.8 kg for two patients. This could be either bysuppressing the production of ghrelin by the gastric fundus and by improvement inadherence to dietary and behavioral measures by patients. Postoperatively there was goodprogress with in-hospital control of episodes of hypoglycemia, persisting afterdischarge.As a side effect, one of the patients complained of heartburn and acid regurgitation,being diagnosed gastroesophageal reflux disease with confirmation by esophageal pHmonitoring with DeMeester score of 17.32. The symptoms were completely controlled withthe use of proton pump inhibitor.The current trend is that no more should be done subtotal pancreatectomy or almostcomplete, in view to morbidity and mortality of this operation, which often is noteffective. Thus, one must make efforts to develop an effective surgical procedure forthe treatment of hyperinsulinemic hypoglycemia after gastric bypass facing the realpathophysiology of the condition, trying to maintain the weight loss.The procedure to reestablish the food transit through the duodenum and proximal jejunum,keeping the restrictive component of gastric bypass in the treatment of hyperinsulinemichypoglycemia, showed good initial results that can validate its use in other cases.


Understanding soil erosion by water is essential for a range of research areas but the predictive skill of prognostic models has been repeatedly questioned because of scale limitations of empirical data and the high variability of soil loss across space and time scales. Improved understanding of the underlying processes and their interactions are needed to infer scaling properties of soil loss and better inform predictive methods. This study uses data from multiple environments to highlight temporal-scale dependency of soil loss: erosion variability decreases at larger scales but the reduction rate varies with environment. The reduction of variability of the geomorphic response is attributed to a ‘compensation effect’: temporal alternation of events that exhibit either source-limited or transport-limited regimes. The rate of reduction is related to environment stochasticity and a novel index is derived to reflect the level of variability of intra- and inter-event hydrometeorologic conditions. A higher stochasticity index implies a larger reduction of soil loss variability  with respect to the mean hydrologic forcing, offering a promising indicator for estimating the degree of uncertainty of erosion assessments. Estimates of upland soil loss have been used as essential input information in a range of analyses, such as identification of the effects of soil erosion on global environmental costs, agricultural productivity, and carbon and nutrient cycling17811131415In erosion research, such a space- and time-scale dependency has long been addressed. The spatial aspect has been explored in numerous experimental studies through scaling from micro to macro domains192219232426compensation and soil substrate stabilization, (2) we further illustrate that the uncertainty of soil loss is related to stochasticity (the degree of intra- and inter-event variations) of hydrometeorologic conditions. Finally, (3) we derive a novel index that offers the convenience of simplicity and thus can be used in practical, large-scale erosion assessment applications. As a result, we contend that properly informed bounds of uncertainty must accompany soil loss estimate at each scale.Using the extensive Universal Soil Loss Equation USLE, databasMethods). The data indicate the high variability/non-uniqueness at the three temporal scales, expressed as the order of difference (ΔO) for all locations. Interesting features that emerge from the USLE data are a reduction of the range of variability for coarser, aggregated temporal scales , The proposed hypothesis considers the dependence of variability of geomorphic response on temporal scale and environment. To address this effect, we introduce the notions of soil loss ‘compensation’ and ‘stabilization’. ‘Compensation’ refers to temporal alternation of events that are effective in transporting sediment , and those that are mostly limited to breaking down soil matrix, without moving the bulk of perturbed materials . Due to the stochastic nature of variations of hydrometeorologic conditions, the chance that the occurrence of one type of event is ‘compensated’ by that of the other grows with temporal scale. This, for example, refers to the chance of occurrence of lower or higher rainfall, drier or wetter antecedent moisture conditions, which all exhibit different chances of runoff production and overland flow occurrence. Using two scenarios  are carried out that use identical rainfall with the same initial hydrologic condition, except for antecedent soil substrate state that is continuously updated  of hydrometeorologic conditions should lead to a higher chance for compensation and thus a larger reduction in geomorphic response variability at coarser temporal scales. Very small stochasticity of hydrometeorologic conditions  can be viewed as the driving cause for system quasi-stabilization, implying that variability of geomorphic response at different temporal scales is comparable and generally smaller than that in environments with high stochasticity. Between the two limiting cases, one can expect a range of dynamics that should exhibit a correlation between the reduction of geomorphic response variability across aggregation scales and the degree of stochasticity of hydro-environment.If the proposed concept of the ‘compensation’ effect is correct, higher stochasticity , which is defined as the sum of three relative entropy indices for the variables of observed 30-minute rainfall intensity (RI), total rainfall volume (TR), and runoff ratio (RR) that represent rainfall intensity, rainfall amount, and a scaled measure of the hydrological response, respectively. The relative entropy quantifies the extent of stochastic variability of each variable: it is zero in environments with high stochastic variability and is maximized in absolute value for environments with homogeneous conditions. For example, as can be concluded from RI, TR, and RR for the location Clarinda, IA, exhibit higher stochasticity and thus their entropy magnitudes are relatively closer to zero when compared to the other locations, such as Arnot, NY. The stochasticity index computed for the USLE locations is positively related to the reduction of soil loss variability between event and annual scales  and erodibility (soil) factors. The effect of variability reduction identified here therefore ensured that past decisions of long-term planners have been already cushioned, to some extent, from the higher uncertainty that accompany estimates from data collected over shorter periods. The missing element however remains an explicit inclusion of uncertainty into the assessment equations. One possible approach could be the development of a probabilistic framework that may contemplate ideas from the hydrologic frequency analysis of extremes or landslide occurrence, such as events of specific recurrence intervals and the probability of occurrence of soil loss corresponding to a given percentile range. Such probabilistic approaches would contribute to more appropriate planning tools for long-term assessments.What are the practical implications? Due to the overall high variability of soil loss with respect to runoff at typical time scales of empirical observation, erosion predictive skill is likely to remain handicapped even in when accurate runoff data are available. An optimistic view on the problem is however that the skill appears to be asymptotically consistent for larger temporal scales, albeit the skill convergence will depend on site location, as illustrated here. In general, policy makers or managers have already relied on long-term estimate of soil loss. For example, the U.S. Department of Agriculture developed the National Resources Inventory NRI that useWe introduce a stochasticity index, which expresses the degree of intra- and inter-event variations of environmental conditions. The reduction of geomorphic response variability from the event to the annual scales is linearly (positively) related to the index, corroborating the hypothesis that the high stochasticity of hydrometeorologic forcing increases the chance of the ‘compensation effect’ and reduce uncertainty in the long-term. Conversely, weak stochasticity of the forcing increases the temporal scales at which the ‘compensation effect’ can be considered valid. A practical implication is that the stochasticity index could be a promising parsimonious indicator in estimating the degree of assessment uncertainty, when only a single average soil loss estimate is used in a management decision. However, the developed relationship  is derivhttp://topsoil.nserl.purdue.edu/usle). Many locations contain observations made for replicated plots, the number of which varies over time. For such plots, experimental conditions in terms of hydrometeorologic forcing, plot slope, soil type, and landuse were identical. Data from these replicated plots were included in the analysis because the data represent possible variability of soil loss within a plot that is subject to the same climate forcing and land conditions. After elimination of events for which plot replications were not consistently used, the analysis data set used here includes 884 erosion events for 10 locations , with the number of replicated plots among given locations varying between 4 and 16. Calendar years are used to compute averages at the annual aggregation scale. To estimate values at the 5-year aggregation scale, moving average over five consecutive calendar years is carried out resulting in correlated 5-year averages . The order of magnitude difference (ΔO) is computed as the difference of the common logarithm of data values and values obtained from log-linear regression between runoff and soil loss.The USLE database contains storm characteristics , runoff, soil loss, and site-specific description. The data consist of over 11,000 plot-years of observations at 47 locations in the U.S. The current availability is however limited to 3,195 plot-years  at 14 field sites (H) of highly erodible deposited soil and that (1-H) of original, “intact” soil, in which contact forces hold particles together. While the soil surface is allowed to change during the simulation due to the local processes of erosion and deposition, at the event-scale, the feedback of change in elevation and slope to hydrologic processes is weak. Therefore, one-way coupling between hydrology and erosion processes is used in the study.The tRIBS-VEGGIE-FEaST  is used. The model partitions energy budget at surface303334Numerical representation of the domain , the boundary and initial conditions for surface and subsurface domains, soil properties , and details on numerical experiments for RI), total rainfall volume (TR), and runoff ratio (RR), as reported in the USLE database, normalized by the respective average values were computed .


M. tuberculosis (Mtb), and over the last decade only a few studies demonstrated the importance of PTMs to the pathobiology and antigenicity of select proteins in Mtb, M. bovis, and Mycobacterium avium subsp. paratuberculosis (MAP). In this communication we present the opinion that in a world of cross-reactive epitopes, and high amino acid sequence similarity between M. bovis, MAP, and their saprophytic counterparts, PTM diversity amongst these species may confer a new level of epitope-specificity for select antigens. We will also highlight that in the case of protein glycosylation, the type and extent of glycosyl moieties should not been seen as having the same outcome. Furthermore, the presence or absence of the PTM of proteins included in subunit vaccine formulations or attenuated strains, may enhance or mask the processing, presentation, and immunogenicity of relevant epitopes. Collectively, these data call to action critical analyses of the components we use to formulate mycobacterial vaccines. As the vast majority of PTM studies have focused on glycosylation, this PTM will be the focal point of discussion.Over the last two decades significant research efforts and resources have been devoted to identifying mycobacterial proteins of value to diagnostic assays and vaccine formulations. These scientific endeavors were often preceded by first identifying a target population of proteins, for example cytoplasmic, cell envelope, or extracellular. However, many of these endeavors have overlooked the posttranslational modifications (PTM) to which these protein subsets may be targets of. Consequently, we may be missing essential molecular information relevant to the function and antigenicity of these effector molecules, and in turn the pathobiology of these bugs. Moreover, heterologous expression of mycobacterial proteins in hosts lacking homologous PTM systems negates any functional and/or antigenic role the PTM may impart. Functional and pathogenic roles of PTMs, such as protein glycosylation, have been reported for other Gram-positive bacteria, especially in reference to mucosal pathogens  why variation in glycosylation results in an altered immunological response.Espitia and Mancilla  first idRv1002c mutant. Murine alveolar macrophages co-cultured with the ΔRv1002c mutants showed a 50% reduction in uptake over H37Rv. Moreover, median survival of SCID mice challenged with the ΔRv1002c mutants increased by 41 days over H37Rv. Collectively, these data highlight the significant contribution of glycoproteins to infectivity and virulence of Mtb. In another study, MS mapping of the M.bovis glycoprotein MPB83 identified a unique mannose linkage not previously reported in Mtb glycoproteins  that exclusively require their PTM for antigenicity, (ii) where the PTM is dispensable for protective immunity, and (iii) containing new subsets of protective or relevant antigens that had been masked by the presence of a PTM.The complexity of glycosylation in addition to the consequences it carries calls to action a bottom-up approach in screening for novel vaccine candidates. The potential of these effector molecules to contain species-specific glycosylation markers may benefit vaccine formulations, in addition to diagnostic assays. The technical hurdles in obtaining the necessary quantity and fidelity of glycoproteins from slower growing The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.