First-order antiferromagnetic transitions of SrMn2P2 and CaMn2P2 single crystals containing corrugated-honeycomb Mn sublattices.

SrMn2P2 and CaMn2P2 are insulators that adopt the trigonal CaAl2Si2-type structure containing corrugated Mn honeycomb layers. Magnetic susceptibility χ and heat capacity versus temperature T data reveal a weak first-order antiferromagnetic (AFM) transition at the Néel temperature [Formula: see text] K for SrMn2P2 and a strong first-order AFM transition at [Formula: see text] K for CaMn2P2 Both compounds exhibit isotropic and nearly T-independent [Formula: see text], suggesting magnetic structures in which nearest-neighbor moments are aligned at [Formula: see text] to each other. The 31P NMR measurements confirm the strong first-order transition in CaMn2P2 but show critical slowing down above [Formula: see text] for SrMn2P2, thus also evidencing second-order character. The 31P NMR measurements indicate that the AFM structure of CaMn2P2 is commensurate with the lattice whereas that of SrMn2P2 is incommensurate. These first-order AFM transitions are unique among the class of (Ca, Sr, Ba)Mn2 (P, As, Sb, Bi)2 compounds that otherwise exhibit second-order AFM transitions. This result challenges our understanding of the circumstances under which first-order AFM transitions occur.

Normothermic Ex Vivo Machine Perfusion of Discarded Human Pancreas Allografts: A Feasibility Study.

Pancreas transplantation is the only curative treatment for patients with complicated diabetes, and organ shortage is a common and increasing problem. Strategies to expand the donor pool are needed, and normothermic ex vivo perfusion of the pancreas has the potential to test and repair grafts before implantation. Between January 2021 and April 2022, six human pancreases, declined for transplantation or islet isolation, were perfused using a previously established method by our group. All 6 cases were successfully perfused for 4 h, with minimal edema. The mean age of the donors was 44.16 ± 13.8 years. Five grafts were obtained from neurological death donors, and one was obtained from a donation after cardiac death. The mean glucose and lactate levels decreased throughout perfusion and insulin levels increased. All 6 grafts were metabolically active during perfusion and histopathology showed minimal tissue injury and no edema. Human normothermic ex vivo perfusion of the pancreas is feasible and safe and has the potential to expand the donor pool. Future studies will focus on tests and biomarkers for the assessment of grafts.

Normothermic ex situ pancreas perfusion for the preservation of porcine pancreas grafts.

Pancreas transplantation improves and extends the life of patients with insulin-dependent diabetes. Pancreata from extended criteria donors have been increasingly used due to the scarcity of available grafts. Normothermic ex situ pancreas perfusion (NESPP) can keep grafts metabolically active, potentially allowing for assessment and organ repair, and could improve outcomes of marginal grafts. A novel NESPP technique was developed and tested. Porcine pancreata were removed after a short period of warm ischemia and subjected to 6 h of NESPP. Perfusion parameters, potential graft assessment markers and graft injury were measured. Next, pancreata subjected to 3 h of NESPP were transplanted and animals were followed for up to 3 days. Graft function and injury post-transplantation were evaluated. Using this novel system of perfusion, pancreata were perfused for an extended period of time with minimal edema. Histology at the end of perfusion showed intact islet cells with only mild signs of tissue injury. NESPP transplanted grafts showed immediate function after transplantation, with glucose levels in normal range. NESPP maintains a physiologic environment and excellent graft function without causing significant graft injury. Porcine pancreas transplantation is feasible and allows for in vivo graft assessment of pancreas function and injury after NESPP.

Preoperative and Postoperative Approaches to Gastroesophageal Cancer: What is All the Fuss About.

Gastroesophageal cancers carry poor prognoses, and are a leading cause of cancer-related morbidity and mortality worldwide. Even in those with resectable disease, more than half of patients treated with surgery alone experience disease recurrence. Multimodality approaches using preoperative and postoperative chemotherapy and/or radiotherapy have been established, resulting in incremental improvements in outcomes. Globally, there is no standardized approach, and treatment varies with geographic location. The question remains of how to select the optimal perioperative treatment that will maximize benefit for patients while avoiding toxicities from unnecessary therapies. This article reviews currently available evidence supporting preoperative and postoperative therapy in gastroesophageal cancers, with an emphasis on recent practice-changing trials and ongoing areas of investigation, including the role of immune checkpoint inhibition and biomarker-guided treatment.

Palliative Care Challenges and Strategies for the Management Amid COVID-19 Pandemic in India: Perspectives of Palliative Care Nurses, Cancer Patients, and Caregivers.

The WHO selected 2020 to recognize the work of nurses and midwives because it is the bicentenary of the birth of the founder of modern nursing, Florence Nightingale. It has been demonstrated amply now as the nurses are the largest sector of health-care workers in every country, playing a pivotal role in response to the novel coronavirus (COVID-19) pandemic worldwide. Every day, nurses are working tirelessly by leaving their homes to assist the sick, allay community fears, and address concerns. This article is written by interviewing the staff nurses working in the wards/outpatient departments of a reputed palliative care center in Karnataka State, reviewing the recent nurses' blogs, editorial commentaries, WHO guidelines, CDC guidelines, and recent short communications on COVID-19 pandemic. The authors in this article attempted to address the palliative care challenges and strategies for the management during the COVID-19 pandemic in India.

Anomalous Composition-Induced Crossover in the Magnetic Properties of the Itinerant-Electron Antiferromagnet Ca_{1-x}Sr_{x}Co_{2-y}As_{2}.

The inference of Ying et al. [Europhys. Lett. 104, 67005 (2013)EULEEJ0295-507510.1209/0295-5075/104/67005] of a composition-induced change from c-axis ordered-moment alignment in a collinear A-type antiferromagnetic (AFM) structure at small x to ab-plane alignment in an unknown AFM structure at larger x in Ca_{1-x}Sr_{x}Co_{2-y}As_{2} with the body-centered tetragonal ThCr_{2}Si_{2} structure is confirmed. Our major finding is an anomalous magnetic behavior in the crossover region 0.2≲x≲0.3 between these two phases. In this region the magnetic susceptibility vs temperature χ_{ab}(T) measured with magnetic fields H applied in the ab plane exhibit typical AFM behaviors with cusps at the Néel temperatures of ∼ 65 K, whereas χ_{c}(T) and the low-temperature isothermal magnetization M_{c}(H) with H aligned along the c axis exhibit extremely soft ferromagneticlike behaviors.

Effective One-Dimensional Coupling in the Highly Frustrated Square-Lattice Itinerant Magnet CaCo_{2-y}As_{2}.

Inelastic neutron scattering measurements on the itinerant antiferromagnet CaCo_{2-y}As_{2} at a temperature of 8 K reveal two orthogonal planes of scattering perpendicular to the Co square lattice in reciprocal space, demonstrating the presence of effective one-dimensional spin interactions. These results are shown to arise from near-perfect bond frustration within the J_{1}-J_{2} Heisenberg model on a square lattice with ferromagnetic J_{1} and hence indicate that the extensive previous experimental and theoretical study of the J_{1}-J_{2} Heisenberg model on local-moment square spin lattices should be expanded to include itinerant spin systems.

Electron transport within transparent assemblies of tin-doped indium oxide colloidal nanocrystals.

Stripe-like compact assemblies of tin-doped indium oxide (ITO) colloidal nanocrystals (NCs) are fabricated by stop-and-go convective self-assembly (CSA). Systematic evaluation of the electron transport mechanisms in these systems is carried out by varying the length of carboxylate ligands protecting the NCs: butanoate (C4), octanoate (C8) and oleate (C18). The interparticle edge-to-edge distance L0, along with a number of carbon atoms in the alkyl chain of the coating ligand, are deduced from small-angle x-ray scattering (SAXS) measurements and exhibit a linear relationship with a slope of 0.11 nm per carbon pair unit. Temperature-dependent resistance characteristics are analyzed using several electron transport models: Efros-Shklovskii variable range hopping (ES-VRH), inelastic cotunneling (IC), regular island array and percolation. The analysis indicated that the first two models (ES-VRH and IC) fail to explain the observed behavior, and that only simple activated transport takes place in these systems under the experimental conditions studied (T = 300 K to 77 K). Related transport parameters were then extracted using the regular island array and percolation models. The effective tunneling decay constant ßeff of the ligands and the Coulomb charging energy EC are found to be around 5.5 nm(-1) and 25 meV, respectively, irrespective of ligand lengths. The theoretical tunneling decay constant ß calculated using the percolation model is in the range 9 nm(-1). Electromechanical tests on the ITO nanoparticle assemblies indicate that their sensitivities are as high as ∼30 and remain the same regardless of ligand lengths, which is in agreement with the constant effective ßeff extracted from regular island array and percolation models.

High-throughput fabrication of anti-counterfeiting colloid-based photoluminescent microtags using electrical nanoimprint lithography.

This work demonstrates the excellent capability of the recently developed electrical nanoimprint lithography (e-NIL) technique for quick, high-throughput production of well-defined colloid assemblies on surfaces. This is shown by fabricating micron-sized photoluminescent quick response (QR) codes based on the electrostatic directed trapping (so called nanoxerography process) of 28 nm colloidal lanthanide-doped upconverting NaYF4 nanocrystals. Influencing experimental parameters have been optimized and the contribution of triboelectrification in e-NIL was evidenced. Under the chosen conditions, more than 300 000 nanocrystal-based QR codes were fabricated on a 4 inch silicon wafer, in less than 15 min. These microtags were then transferred to transparent flexible films, to be easily integrated onto desired products. Invisible to the naked eye, they can be decoded and authenticated using an optical microscopy image of their specific photoluminescence mapping. Beyond this very promising application for product tracking and the anti-counterfeiting strategies, e-NIL nanoxerography, potentially applicable to any types of charged and/or polarizable colloids and pattern geometries opens up tremendous opportunities for industrial scale production of various other kinds of colloid-based devices and sensors.

Reanimating Pancreatic Grafts Subjected to Prolonged Cold Ischemic Injury Using Normothermic Ex Vivo Perfusion.

Background: Pancreas transplant volumes are limited because of poor utilization of "extended criteria grafts." Prolonged cold ischemia is a risk factor associated with poor allograft survival. We aimed to establish the feasibility of transplantation using grafts subjected to prolonged cold ischemia and determine whether these grafts could be optimized using normothermic ex vivo perfusion (NEVP) in a porcine model. Methods: The study population consisted of 35 to 40 kg male Yorkshire pigs in an allotransplantation model with a 3-d survival plan for recipients. Control grafts were subjected to cold storage (CS) in a University of Wisconsin solution for 21 to 24 h (n = 6), whereas the test group received an additional 3 h NEVP after CS of 21 h (n = 5). Results: The 3-d survival was 60% in the NEVP arm versus 0% in the control arm (P = 0.008; log rank). Graft parenchyma was 60% to 70% preserved in the NEVP arm at necropsy on gross appearance. In addition, the islet function was well preserved, and both the pancreas (including the islets) and the duodenal morphology were maintained histologically. The intravenous glucose tolerance test on the day of euthanasia was in the normoglycemic range for 80% of cases in the NEVP arm. Conclusions: Optimization of pancreas grafts exposed to extended CS with NEVP seems promising at rescuing and reanimating these grafts for transplantation, resulting in significantly improved survival in a porcine pancreas transplant model.

Barrett's Esophagus and Esophageal Adenocarcinoma: A Histopathological Perspective.

Esophageal adenocarcinoma (EAC) is increasing in prevalence. Barrett's esophagus (BE) has long been recognized as the putative precursor lesion for EAC, but much is still unknown regarding its cell of origin and what molecular factors influence its neoplastic progression. Accurate pathologic assessment of BE biopsies is important for identifying patients most at risk of progressing to EAC, whereas pathologic assessment of EAC specimens plays a major role in influencing therapeutic decision-making.

Quantification of the electrostatic forces involved in the directed assembly of colloidal nanoparticles by AFM nanoxerography.

Directed assembly of 10 nm dodecanethiol stabilized silver nanoparticles in hexane and 14 nm citrate stabilized gold nanoparticles in ethanol was performed by AFM nanoxerography onto charge patterns of both polarities written into poly(methylmethacrylate) thin films. The quasi-neutral silver nanoparticles were grafted on both positive and negative charge patterns while the negatively charged gold nanoparticles were selectively deposited on positive charge patterns only. Numerical simulations were conducted to quantify the magnitude, direction and spatial range of the electrophoretic and dielectrophoretic forces exerted by the charge patterns on these two types of nanoparticles in suspension taken as models. The simulations indicate that the directed assembly of silver nanoparticles on both charge patterns is due to the predominant dielectrophoretic forces, while the selective assembly of gold nanoparticles only on positive charge patterns is due to the predominant electrophoretic forces. The study also suggests that the minimum surface potential of charge patterns required for obtaining effective nanoparticle assembly depends strongly on the charge and polarizability of the nanoparticles and also on the nature of the dispersing solvent. Attractive electrostatic forces of about 2 × 10( - 2) pN in magnitude just above the charged surface appear to be sufficient to trap silver nanoparticles in hexane onto charge patterns and the value is about 2 pN for gold nanoparticles in ethanol, under the present experimental conditions. The numerical simulations used in this work to quantify the electrostatic forces operating in the directed assembly of nanoparticles from suspensions onto charge patterns can easily be extended to any kind of colloid and serve as an effective tool for a better comprehension and prediction of liquid-phase nanoxerography processes.

Electron-phonon coupling enhancement and displacive magnetostructural transition in SrCr2 As2 under magneto-Raman spectroscopy.

A Raman spectroscopy study on high quality single crystals of SrCr2 As2 (SCA) in the temperature T range 4 K < T < 300 K and high applied magnetic fields up to H = 9 T is presented. The chromium B 1g phonon analysis reveals two anomalous shifts in the frequency, the first below T = 250 K at H = 0 T in the saturated AFM G-type order likely due to an enhanced electron-phonon coupling by the magnetic order, whereas the second anomaly occurs above H = 4 T at T = 4 K likely as a consequence of a magnetostructural displacive transition. Renormalization of the electronic Raman spectra in both studies reveals a decrease in the electronic density of states with decreasing T and increasing H, respectively, with consequent changes in the Fermi surface, which are intrinsically related to the observed anomalies.

Loss of SMAD4 Is Sufficient to Promote Tumorigenesis in a Model of Dysplastic Barrett's Esophagus.

BACKGROUND & AIMS: Esophageal adenocarcinoma (EAC) develops from its precursor Barrett's esophagus through intermediate stages of low- and high-grade dysplasia. However, knowledge of genetic drivers and molecular mechanisms implicated in disease progression is limited. Herein, we investigated the effect of Mothers against decapentaplegic homolog 4 (SMAD4) loss on transforming growth factor ß (TGF-ß) signaling functionality and in vivo tumorigenicity in high-grade dysplastic Barrett's cells. METHODS: An in vivo xenograft model was used to test tumorigenicity of SMAD4 knockdown or knockout in CP-B high-grade dysplastic Barrett's cells. RT2 polymerase chain reaction arrays were used to analyze TGF-ß signaling functionality, and low-coverage whole-genome sequencing was performed to detect copy number alterations upon SMAD4 loss. RESULTS: We found that SMAD4 knockout significantly alters the TGF-ß pathway target gene expression profile. SMAD4 knockout positively regulates potential oncogenes such as CRYAB, ACTA2, and CDC6, whereas the CDKN2A/B tumor-suppressor locus was regulated negatively. We verified that SMAD4 in combination with CDC6-CDKN2A/B or CRYAB genetic alterations in patient tumors have significant predictive value for poor prognosis. Importantly, we investigated the effect of SMAD4 inactivation in Barrett's tumorigenesis. We found that genetic knockdown or knockout of SMAD4 was sufficient to promote tumorigenesis in dysplastic Barrett's esophagus cells in vivo. Progression to invasive EAC was accompanied by distinctive and consistent copy number alterations in SMAD4 knockdown or knockout xenografts. CONCLUSIONS: Altogether, up-regulation of oncogenes, down-regulation of tumor-suppressor genes, and chromosomal instability within the tumors after SMAD4 loss implicates SMAD4 as a protector of genome integrity in EAC development and progression. Foremost, SMAD4 loss promotes tumorigenesis from dysplastic Barrett's toward EAC.

Prognostic significance of nutritional markers in metastatic gastric and esophageal adenocarcinoma.

BACKGROUND: Malnutrition and sarcopenia are poor prognostic factors in many cancers. Studies in gastric and esophageal (GE) cancer have focused on curative intent patients. This study aims to evaluate the prognostic utility of malnutrition and sarcopenia in de novo metastatic GE adenocarcinoma. METHODS: Patients with de novo metastatic GE adenocarcinoma seen at the Princess Margaret Cancer Centre from 2010 to 2016 with an available pre-treatment abdominal computed tomography (CT) were included. Malnutrition was defined as nutritional risk index (NRI) <97.5. Skeletal muscle index (SMI) was measured at the L3 level (sarcopenia defined as SMI <34.4 cm2 /m2 in women and <45.4 cm2 /m2 in men). Patients receiving chemotherapy had NRI and SMI recalculated at the time of first restaging CT. RESULTS: Of 175 consecutive patients, 33% were malnourished and 39% were sarcopenic at baseline. Patients with pretreatment malnourishment had significantly shorter overall survival (OS; 5.8 vs. 10.9 months, p = 0.000475). Patients who became malnourished during chemotherapy had worse OS compared to those who maintained their nutrition (12.2 vs. 17.5 months p = 0.0484). On univariable analysis, ECOG (p < 0.001), number of metastatic sites (p = 0.029) and NRI (p < 0.001) were significant prognostic factors while BMI (p = 0.57) and sarcopenia (p = 0.19) were not. On multivariable analysis, ECOG (p < 0.001), baseline NRI (p = 0.025), and change in NRI during treatment (p < 0.001) were significant poor prognostic factors for OS. CONCLUSIONS: In de novo metastatic GE adenocarcinoma patients, ECOG, pretreatment NRI and change in NRI were significant prognostic factors for OS while sarcopenia was not. Use of NRI at baseline and during treatment can provide useful prognostic information.

Mutations in the RAS/MAPK Pathway Drive Replication Repair-Deficient Hypermutated Tumors and Confer Sensitivity to MEK Inhibition.

The RAS/MAPK pathway is an emerging targeted pathway across a spectrum of both adult and pediatric cancers. Typically, this is associated with a single, well-characterized point mutation in an oncogene. Hypermutant tumors that harbor many somatic mutations may obscure the interpretation of such targetable genomic events. We find that replication repair-deficient (RRD) cancers, which are universally hypermutant and affect children born with RRD cancer predisposition, are enriched for RAS/MAPK mutations (P = 10-8). These mutations are not random, exist in subclones, and increase in allelic frequency over time. The RAS/MAPK pathway is activated both transcriptionally and at the protein level in patient-derived RRD tumors, and these tumors responded to MEK inhibition in vitro and in vivo. Treatment of patients with RAS/MAPK hypermutant gliomas reveals durable responses to MEK inhibition. Our observations suggest that hypermutant tumors may be addicted to oncogenic pathways, resulting in favorable response to targeted therapies. SIGNIFICANCE: Tumors harboring a single RAS/MAPK driver mutation are targeted individually for therapeutic purposes. We find that in RRD hypermutant cancers, mutations in the RAS/MAPK pathway are enriched, highly expressed, and result in sensitivity to MEK inhibitors. Targeting an oncogenic pathway may provide therapeutic options for these hypermutant polyclonal cancers.This article is highlighted in the In This Issue feature, p. 1307.

Short-range ferromagnetic order due to Ir substitutions in single-crystalline Ba(Co1- x Ir x )2As2 (0 ⩽ x ⩽ 0.25).

The ternary-arsenide compound BaCo2As2 was previously proposed to be in proximity to a quantum-critical point where long-range ferromagnetic (FM) order is suppressed by quantum fluctuations. Here we report the effect of Ir substitutions for Co on the magnetic and thermal properties of Ba[Formula: see text] (0 ⩽ x ⩽ 0.25) single crystals. These compositions all crystallize in an uncollapsed body-centered-tetragonal ThCr2Si2 structure with space group I4/mmm. Magnetic susceptibility measurements reveal clear signatures of short-range FM ordering for x ⩾ 0.11 below a nearly composition-independent characteristic temperature T cl ≈ 13 K. The small variation of T cl with x, thermomagnetic irreversibility between zero-field-cooled and field-cooled magnetic susceptibility versus T, the occurrence of hysteresis in magnetization versus field isotherms at low field and temperature, and very small spontaneous and remanent magnetizations <0.01 µ B/f.u. together indicate that the FM response arises from short-range FM ordering of FM spin clusters as previously inferred to occur in Ca(Co1-x Ir x )2-y As2. Heat-capacity C p(T) data do not exhibit any clear feature around T cl, consistent with the very small moments of the FM clusters. The C p(T) in the paramagnetic temperature regime 25-300 K is well described by the sum of a Sommerfeld electronic contribution and Debye and Einstein lattice contributions where the latter lattice contribution suggests the presence of low-frequency optic modes associated with the heavy Ba atoms in the crystals.

Unsupervised Resolution of Histomorphologic Heterogeneity in Renal Cell Carcinoma Using a Brain Tumor-Educated Neural Network.

PURPOSE: Applications of deep learning to histopathology have proven capable of expert-level performance, but approaches have largely focused on supervised classification tasks requiring context-specific training and deployment. More generalizable workflows that can be easily shared across subspecialties could help accelerate and broaden adoption. Here, we hypothesized that histology-optimized feature representations, generated by a convolutional neural network (CNN) during supervised learning, are transferable and can resolve meaningful differences in large-scale, discovery-type unsupervised analyses. METHODS: We used a CNN, previously trained to recognize brain tumor histomorphologies, to extract 512 feature representations from > 550 digital whole-slide images (WSIs) of renal cell carcinomas (RCCs) from The Cancer Genome Atlas and other previously unencountered tumors. We use these extracted feature vectors to conduct unsupervised image-set clustering and analyze the clinical and biologic relevance of the intra- and interpatient subgroups generated. RESULTS: Within individual WSIs, feature-based clustering could reliably segment tumor regions and other relevant histopathologic subpatterns (eg, adenosquamous and poorly differentiated regions). Across the larger RCC cohorts, clustering extracted features generated subgroups enriched for clinically relevant subtypes (eg, papillary RCC) and outcomes (eg, survival). Importantly, individual feature activation mapping highlighted salient subtype-specific patterns and features of malignancies (eg, nuclear grade, sarcomatous change) contributing to subgroupings. Moreover, some proposed clusters were enriched for recurring, human-based RCC-subtype misclassifications. CONCLUSION: Our data support that CNNs, pretrained on large histologic datasets, can extend learned representations to novel scenarios and resolve clinically relevant intra- and interpatient tissue-pattern differences without explicit instruction or additional optimization. Repositioning of existing histology-educated networks could provide scalable approaches for image classification, quality assurance, and discovery of unappreciated patterns and subgroups of disease.

Impact of adjuvant therapy in patients with a microscopically positive margin after resection for gastric and esophageal cancers.

BACKGROUND: A microscopically positive (R1) resection margin following resection for gastric and esophageal cancers has been documented to be a poor prognostic factor. The optimal strategy and impact of different modalities of adjuvant treatment for an R1 resection margin remain unclear. METHODS: A retrospective analysis was performed for patients with gastric and esophageal adenocarcinoma treated at the Princess Margaret Cancer Centre (PMCC) from 2006-2016. Electronic medical records of all patients with an R1 resection margin were reviewed. Kaplan-Meier and Cox proportional hazards methods were used to analyze recurrence free survival (RFS) and overall survival (OS) with stage and neoadjuvant treatment as covariates in the multivariate analysis. RESULTS: We identified 69 gastric and esophageal adenocarcinoma patients with a R1 resection. Neoadjuvant chemoradiation was used in 13% of patients, neoadjuvant chemotherapy in 12%, surgery alone in 75%. Margins involved included proximal in 30%, distal in 14%, radial in 52% and multiple margins in 3% of patients. Pathological staging showed 3% with stage I disease, 20% stage II and 74% stage III. Adjuvant therapy was given in 52% of R1 pts (28% CRT, 20% chemotherapy alone, 3% radiation alone, 1% reoperation). Median RFS was 14.1 months [95% confidence interval (CI), 11.1-17.2]. The site of first recurrence was 72% distant, 12% mixed, 16% locoregional alone. Median OS was 34.5 months (95% CI, 23.3-57.9) for all patients. There was no significant difference in RFS (adjusted P=0.26) or OS (adjusted P=0.83) comparing modality of adjuvant therapy. CONCLUSIONS: Most patients with positive margins after resection for gastric and esophageal cancer had advanced pathologic stage and prognosis was poor. Our study did not find improved RFS or OS with adjuvant treatment and only one patient had reresection. The main failure pattern was distant recurrence, suggesting that patients being considered for adjuvant radiotherapy (RT) should be carefully selected. Further studies are required to determine factors to select patients with good prognosis despite a positive margin, or those who may benefit from adjuvant treatment.

Mitochondrial DNA mutations and male infertility.

Infertility can be defined as difficulty in conceiving a child after 1 year of unprotected intercourse. Infertility can arise either because of the male factor or female factor or both. According to the current estimates, 15% of couples attempting their first pregnancy could not succeed. Infertility is either primary or secondary. Mitochondria have profound effect on all biochemical pathways, including the one that drivessperm motility. Sperm motility is heavily dependent on the ATP generated by oxidative phosphorylation in the mitochondrial sheath. In this review, the very positive role of mitochondrial genome's association with infertility is discussed.